[Prevention of systemic lupus erythematosus in children born to mothers treated for this disease].

PubMed

Kardaszewicz, E; Machalski, M; Woszczyk, D; Woszczyk, M; Harbut-Gryłka, A

Genetic predisposition and environmental factors (physical, chemical, hormonal and drugs inducing collagen-like syndrome) play an important role in the pathogenesis of the systemic lupus erythematosus. Elimination of these factors from the environment of the genetically predisposed individuals may prevent part of them against the disease. Basing on the above assumption, a chart of prophylaxis has been constructed and distributed among the mothers with the systemic lupus erythematosus, recommending prophylactic measures in both mothers and children. Within 1977-1987, 50 children were examined from time to time. Basic laboratory tests, phenomenon LE, antinuclear antibodies and antibodies anti-DNA have been determined. Transient presence of antinuclear antibodies was seen in 23 children. A tendency to an increase in the antibody titre was observed in girls of this group whereas a decrease in the titre was noted in the boys with the time lapse. Systemic lupus erythematosus prophylaxis in both mothers and children is uncomplicated and favourable for children. Regular determination of antibodies enables early diagnosis of the disease.

Atypical lupus erythematosus panniculitis progressing to antinuclear antibody-negative systemic lupus erythematosus.

PubMed

Pandhi, Deepika; Verma, Prashant; Singal, Archana; Sharma, Sonal; Tondon, Anupama

2012-01-01

Lupus erythematosus panniculitis (LEp) is an uncommon but distinctive subset of lupus erythematosus (LE). It may develop in patients with discoid or systemic LE or may occur as an isolated phenomenon. We describe a case of LEp affecting unusual sites: the parotid gland, eyelid, and scalp. Subsequently, the patient progressed to antinuclear antibody-negative systemic LE.

Commensal microbiota influence systemic autoimmune responses

PubMed Central

Van Praet, Jens T; Donovan, Erin; Vanassche, Inge; Drennan, Michael B; Windels, Fien; Dendooven, Amélie; Allais, Liesbeth; Cuvelier, Claude A; van de Loo, Fons; Norris, Paula S; Kruglov, Andrey A; Nedospasov, Sergei A; Rabot, Sylvie; Tito, Raul; Raes, Jeroen; Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine; Van de Wiele, Tom; Eberl, Gérard; Ware, Carl F; Elewaut, Dirk

2015-01-01

Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life. PMID:25599993

Association of systemic lupus erythematosus with uveitis.

PubMed

Gallagher, Kevin; Viswanathan, Ananth; Okhravi, Narciss

2015-10-01

Systemic lupus erythematosus (SLE) can be associated with uveitis. The reported prevalence of SLE in patients with uveitis varies from 0.1% to 4.8%. Accordingly, the positive predictive value of antinuclear antibody testing in diagnosing SLE in a patient with uveitis varies enormously. An accurate estimate of SLE prevalence in uveitis is needed to establish the value of routine antinuclear antibody testing in patients with uveitis. A literature review using the Medline database was performed to find studies reporting data on uveitis etiology from January 1, 1984, to March 20, 2015. Studies were included where there were sufficient data to draw conclusions on the prevalence of SLE as an etiological factor in uveitis. Data for 53 315 patients were reviewed and 63 studies from 30 countries were included. The prevalence of SLE as a cause of uveitis was estimated to be 0.47% (95% CI, 0.41%-0.53%). The positive predictive value of routine antinuclear antibody testing was 2.9% (95% CI, 2.65%-3.19%). Systemic lupus erythematosus is a rare cause of uveitis. Routine antinuclear antibody testing has a low positive predictive value for SLE. These data suggest such testing should be reserved for patients where there is a higher pretest probability of SLE.

Detection of autoantibodies and increased concentrations of interleukins in plasma from patients with Tourette's syndrome.

PubMed

Cheng, Yu-hang; Zheng, Yi; He, Fan; Yang, Jian-hong; Li, Wen-biao; Wang, Min-ling; Cui, De-yan; Chen, Ying

2012-09-01

The aim of this study was to assess levels of autoantibodies and cytokines in patients with Tourette's syndrome (TS, n = 40) and healthy control individuals (n = 40). Plasma interleukin (IL)-1β, IL-6, IL-17, and soluble gp130 concentrations were significantly higher in the TS group compared with the control group (P < 0.001); whereas the soluble IL-6 receptor concentration was significantly decreased in the TS group compared with the control group (P < 0.001). Significantly more patients in the TS group were positive for antibrain and antinuclear antibodies, and antistreptolysin compared with the control group (P < 0.05). These findings suggest that immune activity is altered in patients with TS.

Prevalence of symptoms of systemic lupus erythematosus (SLE) and of fluorescent antinuclear antibodies associated with chronic exposure to trichloroethylene and other chemicals in well water

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kilburn, K.H.; Warshaw, R.H.

1992-02-01

Criteria for the recognition of systemic lupus erythematosus (SLE) were applied to 362 subjects exposed to trichloroethylene, trichloroethane, inorganic chromium, and other chemicals in water obtained from wells in an industrially contaminated aquifer in Tucson, Arizona. Their antinuclear autoantibodies were measured by fluorescence (FANA) in serum. Ten patients with clinical SLE and/or other collagen-vascular diseases were considered separately. Results were compared to an Arizona control group, to published series, and to laboratory controls. Frequencies of each of 10 ARA symptoms were higher in exposed subjects than in any comparison group except those with clinical SLE. The number of subjects withmore » 4 or more symptoms was 2.3 times higher compared to referent women and men. FANA titers > 1:80 was approximately 2.3 times higher in women but equally frequent in men as in laboratory controls. ARA score and FANA rank were correlated with a coefficient (cc) of .1251, r{sup 2} = .0205 in women and this correlation was almost statistically significant in men cc = .1282, r{sup 2} = .0253. In control men and women neither correlation was significant. Long-term low-dose exposure to TCE and other chemicals in contaminated well water significantly increased symptoms of lupus erthematosus as perceived by the ARA score and the increased FANA titers.« less

T Cell Lipid Rafts and Complement Ligands for Diagnosis and Monitoring of SLE

DTIC Science & Technology

2011-05-01

including complete blood count, erythrocyte sedimentation rate , serum levels of C3 and C4, antinuclear autoantibodies (ANA), and anti-dsDNA level. Tests... sedimentation rate , serum levels of C3 and C4, antinuclear autoantibody (ANA) and anti-dsDNA antibody levels. In addition, each patient underwent history...6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER E-Mail: 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES

Diethylaminoethanol action in the arthritis with Freund adjuvant, in rats.

PubMed

Vrăbiescu, A; Poli, T; Coman, G; Dolcoş, F; Găinaru, C; Carazanu, C; Ciobanu, G

1998-01-01

The authors have studied the action of diethylaminoethanol on Freund adjuvant arthritis, induced in female Lewis rats. They worked on 3 groups, each one including 14 rats, weighing 110-130 g: group I = control; group II = rats injected intracutaneous with 0.1 ml Freund adjuvant; group III = rats injected with Freund adjuvant and treated with diethylaminoethanol i.m. (10 mg/kg body weight), and gel application (2.5%) on paws and tail, daily. During the experiment clinical observations and measurements were made and when the animals were killed, blood was sampled for haematological and immunological assays (CD4, CD8, CD25 T cells and NK cells, antinuclear autoantibody and immune complexes). While in all the rats from group II (without treatment) inflammatory processes developed at the level of the peripheral joints, in group III (diethylaminoethanol treated), these ones were present in only 64% of the rats and by much more reduced forms, followed by a short period of involution. The paw volume, measured with an electronic plethysmometer, was more reduced in the treated rats (7.1-14.2%) than in the non treated ones (27.7-29.3%). The haematologic examination showed an increased number of neutrophiles in both groups with FA injecting. The immunological investigations revealed: a decrease of CD4 cells and an increase of CD8 T cells and NK cells in both groups, a much more decreased level (13.2%) of circulatory immune complexes in treated rats, as compared to the non-treated ones (71.7%). No differences were found regarding the CD25 cells and antinuclear antibodies. The histo-pathological examination showed that the intensity and the extension area of the joint lesions (granulation tissue with fibrous change, cartilage invasion and dilaceration, bone atrophy) were much more reduced in the treated rats. The authors put forward the hypothesis that these effects might be due to diethylaminoethanol antiinflammatory properties.

Antinuclear Antibodies (ANA) in Gordon Setters with Symmetrical Lupoid Onychodystrophy and Black Hair Follicular Dysplasia

PubMed Central

Bohnhorst, J Øvrebø; Hanssen, I; Moen, T

2001-01-01

Antinuclear antibodies (ANA) were demonstrated in 3 out of 10 Gordon setters with symmetrical lupoid onychodystrophy and in 5 out of 13 Gordon setters with black hair follicular dysplasia. Two dogs showed both symmetrical lupoid onychodystrophy and black hair follicular dysplasia, and one of these was ANA positive. The results suggest that symmetrical lupoid onychodystrophy and black hair follicular dysplasia in the Gordon setter might be autoimmune diseases that are pathogenetically related, which might indicate a common genetic predisposition. PMID:11887392

Detection of antinuclear and antilaminin antibodies in autistic children who received thimerosal-containing vaccines.

PubMed

Singh, Vijendra K; Rivas, Wyatt H

2004-01-01

Autism, a neurodevelopmental disorder, may involve autoimmune pathogenesis. Since mercury is potentially a risk factor for autoimmunity, we conducted a study of mercury-induced antinuclear and antilaminin antibodies in autistic and normal children who had been pre-administered with thimerosal-containing vaccines. Laboratory analysis by different immunoassays showed that the serum level of these two autoimmune markers did not significantly differ between autistic and normal children. This finding suggests that the mercury as in thimerosal-containing vaccines is likely not related to autoimmune phenomenon in autism.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus.

PubMed

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-12-01

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients.

The Prevalence of Thyroid Dysfunction in Patients With Systemic Lupus Erythematosus

PubMed Central

Rasaei, Nakisa; Shams, Mesbah; Kamali-Sarvestani, Eskandar; Nazarinia, Mohammad Ali

2015-01-01

Background: Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease caused by immune system-mediated tissue damage. Autoimmune thyroiditis (AT) is an organ-specific disease associated with production of a variety of antibodies such as antinuclear antibodies, anti-double-stranded DNA, anti-Ro antibodies and anti-cardiolipin antibodies. Objectives: The aim of this study was to evaluate the prevalence of thyroid dysfunction and thyroid auto-antibodies in patients with SLE and its relation to SLE disease and other autoantibodies. Patients and Methods: This was a case-control study. The study included a total of 88 patients with SLE and 88 age- and sex-matched healthy volunteers as control group. Two study groups were compared regarding thyroid function test, antinuclear antibody (ANA), antibodies to double-stranded DNA (dsDNA), anti- thyroglobulin antibody (anti-Tg), and anti-thyroid peroxidase (anti-TPO) antibody. Results: The mean age of SLE patients and controls were 32.16 ± 9.19 and 32.48 ± 9.47 years, respectively (P = 0.821). Patients had significantly higher prevalence (43.2% vs. 23.9%; P = 0.015) and titers (221.8 ± 570.5 vs. 78.2 ± 277.2; P = 0.036) of antibodies to Tg compared to controls. The patients had significantly lower titers of T3 compared to controls (125.2 ± 35.6 vs. 136.2 ± 26.5; P = 0.021). The titers of T4, TSH and anti-TPO antibody did not differ significantly between the two study groups. Conclusions: Thyroid dysfunction was not higher in SLE patients compared to healthy individuals. However, anti-Tg antibodies were higher in SLE patients. It has not yet been established that thyroid function tests should be performed routinely in SLE patients. PMID:26756002

The relationship between early ego strength and adolescent responses to the threat of nuclear war

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andrekus, N.J.

Ego resiliency and ego control, measured when subjects were 3 or 4 years old, were related to expectation of war, concern for the future, and activism in response to the threat of nuclear war, measured when subjects were 18 years old. Data from 92 participants in a longitudinal study of ego and cognitive development conducted by Jeanne and Jack Block at the University of California, Berkeley were used to test hypotheses. Assessments with the California Child Q-set, composited across multiple independent observers, provide measures of ego resiliency and ego control. Adolescent interviews regarding the perception of likelihood of nuclear war,more » how this affects their future, and their antinuclear and general political activism were scaled and rated. Early ego resiliency and ego under control were hypothesized to account for the variance in adolescent nuclear responses and activism. The only significant longitudinal relationships were in the female sample, where ego under control was found to be a significant predictor of both general political activism (p<.01) and ideas of the future being affected by the nuclear threat (p<.05). Among males, the relationship between early ego resiliency and adolescent antinuclear activism approached significance (p<.10). Adolescent personality was significantly related to several measures of nuclear response. In girls, adolescent ego under control related to perception of likelihood of nuclear war (p<.05) and antinuclear activism (p<.05), and the interaction of ego resiliency and ego under control predicted general political activism (p<.0005). In boys, adolescent ego resiliency correlated with antinuclear activism (p<.05). These findings were discussed in terms of antecedent parenting styles, and conceptual links were drawn between children's ego resiliency and security of attachment, perspective taking, and moral development.« less

Effect of total lymphoid irradiation on levels of serum autoantibodies in systemic lupus erythematosus and in rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanay, A.; Schiffman, G.; Strober, S.

1986-01-01

The effects of total lymphoid irradiation (TLI) on serum levels of autoantibodies, and of antibodies to diphtheria toxoid, tetanus toxoid, and pneumococcal polysaccharide in patients with lupus nephritis were compared with those previously observed in rheumatoid arthritis (RA) patients. Baseline levels of antibodies to diphtheria toxoid and tetanus toxoid decreased significantly after TLI in patients with lupus and RA, but antibody levels to pneumococcal polysaccharide remained unchanged. After TLI, the levels of antinuclear and anti-DNA antibodies were reduced significantly in lupus, but levels of rheumatoid factor, antinuclear, and antigranulocyte antibodies all tended to increase in RA.

Elevated antinuclear antibodies and altered anti-Epstein-Barr virus immune responses.

PubMed

Cuomo, Laura; Cirone, Mara; Di Gregorio, Ana Oliva; Vitillo, Marina; Cattivelli, Marina; Magliocca, Vittoria; Maiorano, Silvana; Meledandri, Marcello; Scagnolari, Carolina; La Rocca, Sebastiano; Trivedi, Pankaj

2015-01-02

It has been shown that Epstein-Barr virus (EBV) is able to alter the immune response towards self-antigens and may enhance risk of autoimmune diseases such as systemic lupus erythematosus (SLE) in genetically predisposed individuals. In this study, we evaluated the specific antibody immune response against EBV in patients with anti-nuclear autoantibodies (ANA) in comparison with ANA-negative healthy controls. For this purpose, 92 patients with an high anti-ANA reactivity with or without concomitant extractable nuclear antigen (ENA) or double stranded DNA (dsDNA) positivity were selected and compared with 146 healthy donors. We found that anti-EBV-VCA and EA IgG concentrations were significantly higher in ANA-positive patients in comparison to the controls (VCA P<0.0001 and EA P<0,03) as well as in those ANA-positive patients that showed a concomitant ENA positivity (P=0.0002). Interestingly, elevated anti-EBNA-1 IgG was found in a group of patients who had anti SSA/Ro antibodies. Anti-VCA IgM Abs were more frequently found in those patients with a very high titer of ANA (P=0.06); moreover detection of anti-VCA IgM/IgG in absence of anti-EBNA-1 IgG was more frequent in the patient than in the control group. Both these conditions correlate with a recent EBV infection or reactivation. The data suggest that EBV, particularly during acute infection or in its reactivation phase, could be involved in the ANA and ENA autoantibody formation. Copyright © 2014 Elsevier B.V. All rights reserved.

[Detection and the production mechanism of antinuclear antibodies (ANA) and anti-liver/kidney microsomal tpe 1 antibodies (anti-LKM1) in patients with chronic hepatitis C].

PubMed

Bai, Li; Lu, Hai-Ying; Feng, Zhen-Ru; Yu, Min; Li, Wen-Gang; Gong, Wei-Bo; Zhao, Nu-en-ji-ya; Xu, Xiao-Yuan

2009-08-01

To investigate the prevalence of antinuclear antibodies (ANA) and anti-liver/ kidney microsomal type 1 antibodies (anti-LKM1) in patients with chronic hepatitis C (CHC)and to explore the mechanism of production of these autoantibodies. Serum samples were collected from 360 patients with CHC (case group), 69 patients with chronic hepatitis B (CHB) and 69 patients with autoimmune hepatitis (AIH) (control group). Serum ANA and anti-LKM1 were detected by indirect immunofluorescence (HF) technique and enzyme-linked immunosorbent assay (ELISA), respectively. Multi-factor analysis was performed to explore the correlations of the production of autoantibodies with some factors such as age, sex, viral loads, HCV genotype, biochemical parameters and clinical characteristics. Fifty-four (15%) of 360 patients infected with HCV were positive in autoantibodies. The prevalence of ANA and anti-LKM1 were 12.5% (45/360) and 2.5% (9/ 360), respectively. The positive rate of autoantibodies in patients with CHC was significantly higher than that in patients with CHB (15% vs 2.9%, P = 0.006), but significantly lower than that in patients with AIH (15% vs 47.9%, P < 0.001). Twenty-one (11.35%) of 185 male patients and 33 (18.86%) of 175 female patients were positive in autoantibodies, the difference in positive rate was significant (P < 0.05). HCV virus loads in the autoantibodies negative group were higher than that in the autoantibodies positive group (7.2 x 10(7) copies/L vs 1.23 x 10(7) copies/L, P < 0.05). There were not significant differences in age and genotype between the autoantibody positive group and the autoantibody negative group. The serum biochemical parameters of the autoantibody positive group were similar to those of the autoantibody negative group. The differences were not significant for the course of disease, clinical symptom, the incidence of cirrhosis between the autoantibody positive group and the autoantibody negative group. The prevalence of autoantibodies was not different for patients with or without interferon treatment (P > 0.05). Autoantibodies related to AIH can be detected in CHC patients; interferon may not induce the production of autoantibodies; it is very likely that HCV infection induces the autoimmune reaction and the production of autoantibodies.

[Minimal work-up for Raynaud syndrome: a consensus report. Microcirculation working group of the Société française de médecine vasculaire].

PubMed

Pistorius, M-A; Carpentier, P-H

2013-01-01

About ten to fifteen percent of the French population suffer from Raynaud's phenomenon. Most of the time, it is considered as primary Raynaud's phenomenon, without underlying disease. The aim of this expert consensus from the "microcirculation group" for the French Society of Vascular Medicine and the French Society for Microcirculation, was to define clinical guidelines in patients consulting for Raynaud's phenomenon. The recommended minimal screening includes clinical examination, nailfold capillaroscopy and antinuclear antibodies. In particular, the aim of this screening is to identify patients with a significant risk for scleroderma, who would need a careful follow up. Copyright © 2013. Published by Elsevier Masson SAS.

Prevalence and clinical significance of antinuclear antibodies in Iranian women with unexplained recurrent miscarriage

PubMed Central

Molazadeh, Morteza; Karimzadeh, Hadi; Azizi, Mohammad R

2014-01-01

Background: Antinuclear antibodies (ANAs) in women with recurrent miscarriage have been reported. The presence of moderate to high titers of these antibodies represents an autoimmune condition that can endanger the health of the fetus in pregnant women. Objective: In this study, we evaluated the prevalence of ANAs in Iranian women with a history of two or more unexplained abortion. Materials and Methods: 560 women with unexplained recurrent miscarriage and 560 healthy controls accounted for this study over a period of 13 months. ANAs were detected by indirect immunofluorescence technique. Results: ANAs were detected in 74 of 560 (13.21%) patient with recurrent miscarriage, and in only 5 of 560 (0.9%) controls (p<0.001). ANA positivity was generally found with low-positive results (1.40-1.80) in about 38% of positive cases, whereas moderate titres (1.160-1.320) and high titres (>1.640) were seen in about 46% and 16% of cases respectively. Finally evaluating of microscopic ANA patterns revealed that about half of positive cases had antibodies against DNA- histone complex, associated with systemic lupus erythematosus disease. Conclusion: Antinuclear antibodies are not uncommon in women with unexplained recurrent miscarriage, suggesting the possible role of an autoimmune disorder on abortion, at least in a subgroup of patients. PMID:24799884

[Immunodiagnostic methods in lupus erythematosus disseminatus].

PubMed

Storch, H; Schwenke, H; Helbig, W

1975-12-01

In 27 patients with lupus erythematodes diseminatus the determinations of the LE-cells according to the macromethod (Zimmer and Hargraves) and the micromethod (Mudrik and co-workers) were compared with the demonstration of antinuclear factors according to the indirect immunofluorescence and immune enzyme technique. The sensitiveness of the two last-mentioned immunomorphological methods is somewhat larger. In these cases the size of the titre of the antinuclear factor almost always correlates positively with the number of the LE-cells. For the purpose of the initial diagnostics and the judgment of the course a morphological method cannot be renounced, since in the acute episode a high consumption of the antinuclear factor the immunological methods negatively correlate with the number of the LE-cells. The immune enzyme technique is to be recommended on account of the smaller expenditure, permanence of the preparations and high sensitiveness as alternative method of the immunofluorescence technique. In the micromethod the large variation is opposite to the advantage of the slight quantity of blood and to an always existing evaluability. Investigations of the lymphocytes of patients with lupus erythematodes disseminatus by means of the lymphocyte transformation test and the determination of the B-cells with the help of the direct immune peroxidase technique refer to the close pathogenetic connections of cellular and humoral immune reactions in this disease.

Immunomodulatory Effect of Agave tequilana Evaluated on an Autoimmunity Like-SLE Model Induced in Balb/c Mice with Pristane.

PubMed

Gutiérrez Nava, Zúlima Jannette; Jiménez-Aparicio, Antonio Ruperto; Herrera-Ruiz, Maribel Lucila; Jiménez-Ferrer, Enrique

2017-05-25

In this work, the immunomodulatory activity of the acetone extract and the fructans obtained from Agave tequilana were evaluated, on the systemic autoimmunity type-SLE model generated by the administration of 2,6,10,14-tetramethylpentadecane (TMPD, also known as pristane) on Balb/c female mice. The systemic autoimmunity type-SLE was observed seven months after the application of TMPD, in which the animals from the negative control group (animals with damage and without any other treatment) developed articular inflammation, proteinuria, an increment of the antinuclear antibody titters and tissue pro-inflammatory cytokines levels (IL-1β, IL-6, TNF-α e IFN-γ) as well as the anti-inflammatory cytokine IL-10. The administration of the different treatments and the extracts of A. tequilana , provoked the decrease of: articular inflammation, the development of proteinuria, ssDNA/dsDNA antinuclear antibody titters and cytokines IL-1β, IL-6, TNF-α, IFN-γ and IL-10. The phytochemical analysis of the acetone extract identified the presence of the following compounds: β-sitosterol glycoside; 3,7,11,15-tetramethyl-2-hexadecen-1-ol (phytol); octadecadienoic acid-2,3-dihydroxypropyl ester; stigmasta-3,5-dien-7-one; cycloartenone and cycloartenol. Therefore, A. tequilana contains active compounds with the capacity to modify the evolution of the systemic autoimmunity type-SLE on a murine model.

Antinuclear antibody panel

MedlinePlus

... ANA panel; ANA reflexive panel; SLE - ANA; Systemic lupus erythematosus - ANA ... have signs of an autoimmune disorder, particularly systemic lupus erythematosus . This test may be done if you ...

Green Zines: A List of Alternative Environmental Periodicals.

ERIC Educational Resources Information Center

Dodge, Christopher

1992-01-01

Presents an annotated list of 200 alternative environmental periodicals. The list's scope includes animal welfare, vegetarianism, sustainable agriculture, conservation, renewable energy, and antinuclear activism. (MDH)

Antinuclear Antibodies predict a higher number of Pregnancy Loss in Unexplained Recurrent Pregnancy Loss.

PubMed

Sakthiswary, R; Rajalingam, S; Norazman, M R; Hussein, H

The etiology of recurrent pregnancy loss (RPL) is unknown in a significant proportion of patients. Autoimmune processes have been implicated in the pathogenesis. The role of antinuclear antibody (ANA) in this context is largely undetermined. In an attempt to address the lack of evidence in this area, we explored the clinical significance of antinuclear antibody (ANA) in unexplained RPL. We studied 68 patients with RPL and 60 healthy controls from September 2005 to May 2012. All subjects were tested for ANA by immunofluorescence testing, and a titer of 1: 80 and above was considered positive. We compared the pregnancy outcome between the ANA positive and ANA negative RPL cases. The incidence of ANA positivity among the cases (35.3%) was significantly higher than the controls (13.3%) (p=0.005). ANA positive cases showed significantly higher number of RPL (p=0.006) and lower number of successful pregnancies (p=0.013) compared to the ANA negative cases . The ANA titre had a significant association with the number of RPL (p<0.05, r=0.724) but not with the number of successful pregnancies (p=0.054). ANA positivity predicts a less favorable pregnancy outcome in RPL. Our findings suggest that the ANA titre is a useful positive predictor of the number of RPL. Hence, ANA test is a potential prognostic tool for this condition which merits further research.

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2012 CFR

2012-04-01

...), rheumatoid arthritis, Sjogren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues). (b) Classification...

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2011 CFR

2011-04-01

...), rheumatoid arthritis, Sjogren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues). (b) Classification...

Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases

PubMed Central

Mercado, Monica Vázquez-Del; Chan, Edward K. L.

2010-01-01

Autoantibody tests have been used extensively in diagnosis and follow-up of patients in rheumatology clinics. Immunofluorescent antinuclear antibody test using HEp-2 cells is still considered the gold standard for screening of autoantibodies, and most of specific autoantibodies are currently tested by ELISA as a next step. Among the many autoantibody specificities described, some have been established as clinically useful diagnostic markers and are included in the classification criteria of diseases. Despite a long history of routine tests and attempts to standardize such assays, there are still limitations and problems that clinicians need to be aware of. Clinicians should be able to use autoantibody tests more efficiently and effectively with a basic knowledge on the significance of and potential problems in autoantibody tests. PMID:19277826

Gemcitabine-induced hemolytic uremic syndrome mimicking scleroderma renal crisis presenting with Raynaud's phenomenon, positive antinuclear antibodies and hypertensive emergency.

PubMed

Yamada, Yuichiro; Suzuki, Keisuke; Nobata, Hironobu; Kawai, Hirohisa; Wakamatsu, Ryo; Miura, Naoto; Banno, Shogo; Imai, Hirokazu

2014-01-01

A 58-year-old woman who received gemcitabine for advanced gallbladder cancer developed an impaired renal function, thrombocytopenia, Raynaud's phenomenon, digital ischemic changes, a high antinuclear antibody titer and hypertensive emergency that mimicked a scleroderma renal crisis. A kidney biopsy specimen demonstrated onion-skin lesions in the arterioles and small arteries along with ischemic changes in the glomeruli, compatible with a diagnosis of hypertensive emergency (malignant hypertension). The intravenous administration of a calcium channel blocker, the oral administration of an angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker and the transfusion of fresh frozen plasma were effective for treating the thrombocytopenia and progressive kidney dysfunction. Gemcitabine induces hemolytic uremic syndrome with accelerated hypertension and Raynaud's phenomenon, mimicking scleroderma renal crisis.

Antinuclear Antibodies (ANA)

MedlinePlus

... Keep me signed in Passwords are Case Sensitive. Ex. Enter smith as follows: Smith Forgot Username/Password? ... Erythematosus (Juvenile) Takayasu's Arteritis Tendinitis & Bursitis Tumor Necrosis Factor Receptor Associated Periodic Syndrome (Juvenile) Vasculitis Enfermedades y ...

ANA (Antinuclear Antibody Test)

MedlinePlus

... findarticles.com . Kavanaugh A, Tomar R, Reveille J, Solomon DH, Homburger HA. Guidelines for clinical use of ... Russell Tomar, MD, John Reveille, MD, Daniel H. Solomon, MD, MPH, and Henry A. Homburger, MD. Guidelines ...

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

...), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues). (b) Classification...

21 CFR 866.5100 - Antinuclear antibody immunological test system.

Code of Federal Regulations, 2013 CFR

2013-04-01

...), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of many body tissues). (b) Classification...

Hepatitis C virus infection can mimic type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis.

PubMed Central

Pawlotsky, J M; Deforges, L; Bretagne, S; André, C; Métreau, J M; Thiers, V; Zafrani, E S; Goossens, M; Duval, J; Mavier, J P

1993-01-01

Hepatitis C virus (HCV) has been shown to induce anti-liver-kidney microsomal-1 (LKM1) antibody positive chronic active hepatitis, simulating type 2 autoimmune chronic active hepatitis. The cases of five patients presenting with features of type 1 (antinuclear antibody positive) autoimmune chronic active hepatitis and extrahepatic autoimmune manifestations, in whom immunosuppressive treatment had no effect on liver disease are presented. In these patients, HCV infection could be shown by the presence in serum of anti-HCV antibodies and HCV-RNA detected by polymerase chain reaction. These cases suggest the following: (a) chronic HCV infection can mimic type 1, as well as type 2, autoimmune chronic active hepatitis; (b) HCV infection might be systematically sought in patients presenting with features of type 1 autoimmune chronic active hepatitis, with special care in patients who are unresponsive to immunosuppressive treatment. Images Figure PMID:7686122

Lupus erythematosus cells in bone marrow: the only clue to a previously unsuspected diagnosis of systemic lupus erythematosus.

PubMed

Pujani, Mukta; Kushwaha, Shivani; Sethi, Neha; Beniwal, Anu; Shukla, Shailaja

2013-01-01

Systemic lupus erythematosus (SLE) is an autoimmune multisystem disease characterized by the development of antinuclear antibodies. Nowadays considered outdated, lupus erythematosus (LE) cell preparation served as a screening test for SLE for decades. However, the importance of discovering LE cells on routine cytology cannot be overemphasized. We report the case of a 30-year-old female in whom bone marrow aspiration (BMA) was performed during an investigative workup for pyrexia of unknown origin. The observation of LE cells in direct bone marrow smears (without the use of an anticoagulant) raised the suspicion of SLE, which was later confirmed by antinuclear antibody testing. In the present case, LE cells were observed on BMA performed for the investigation of fever of unknown origin. The unexpected observation of LE cells in BMA smears emphasizes the fact that good morphological observation of marrow aspirates can provide crucial clues to a previously unsuspected diagnosis.

In defiance of nuclear deterrence: anti-nuclear New Zealand after two decades.

PubMed

Reitzig, Andreas

2006-01-01

In 1984, nuclear-armed and nuclear-powered vessels were banned from New Zealand to express the country's rejection of the nuclear deterrence concept. This led to a disagreement with the United States. Today, the ban on nuclear-powered ships is the only element of the nuclear-free legislation that still strains US-New Zealand relations. This article presents the reasons for the ban on nuclear-powered ships, which include scientific safety concerns, a symbolic rejection of the nuclear deterrence posture, and patriotic factors such as a nuclear-free national identity. The military and economic consequences of the ban are also examined. Since the ban on nuclear-powered vessels appears to be neither widely known abroad nor commonly recognised as a supportive disarmament measure outside New Zealand, it is concluded that whatever the future of this ban will be, New Zealand's anti-nuclear image will remain known internationally through the ban on nuclear arms.

Poly IC therapy in aleutian disease of mink.

PubMed Central

Russell, A S; Percy, J S; Cho, H J

1975-01-01

Twenty-four virgin female aleutian mink were infected with aleutian disease agent and after 24 hours, 12 of these were treated with a course of polyinosinic acid-polycytidilic acid (Poly IC) injections. After six weeks the gammaglobulin level was significantly lower in the treated group but at 12 weeks this difference was no longer present. Four of the treated mink had normal target organ histology when killed at 20 weeks. The untreated group all showed moderate to marked changes but this difference was not statistically significant. There was a marked increase in the reactive lymphocyte blastogenesis index during the first weeks of infection and the phytohaemagglutinin response was seen to fall progressively. The antiglobulin reaction usually became positive after infection but neither antinuclear nor antierythrocyte antibodies were found. Precipitating antibodies to several polynucleotides were frequently present and were unrelated to infection or to Poly IC treatment. Images Fig. 1. Fig. 2A Fig. 2B. PMID:1095164

ICARE improves antinuclear antibody detection by overcoming the barriers preventing accreditation.

PubMed

Bertin, Daniel; Mouhajir, Yassin; Bongrand, Pierre; Bardin, Nathalie

2016-02-15

Antinuclear antibodies (ANA) are useful biomarkers for the diagnosis and the monitoring of rheumatic diseases. The American College of Rheumatology has stated that indirect immunofluorescence (IIF) analysis remains the gold standard for ANA screening. However, IIF is time consuming, subjective, not fully standardized and presents several issues for accreditation which is the process leading to ISO 15189 certification for medical laboratories. We propose an innovative tool for accreditation by using the quantitative evaluation of the automated image capture and analysis "ICARE" (Immunofluorescence for Computed Antinuclear antibody Rational Evaluation). We established the optimal screening dilution (1:160) and a fluorescence index (FI) cutoff for ICARE on a cohort of 91 healthy blood donors. Then, we evaluated performance of ICARE on a routine cohort of 236 patients. Precision parameters of ANA detection by IIF were evaluated according to ISO 15189. ICARE showed an excellent concordance with visual evaluation (88%, Kappa=0.76) and significantly discriminated between weak to moderate (1:160-1:320 titers) and high (>1:320 titers) ANA levels. A significant correlation was found between FI and ANA titers (Spearman's ρ=0.67; P<0.0001). Using ICARE, we reported precision parameters such as repeatability (CV<13.8%) and reproducibility (CV<13.1%) as well as absence of inter-sample contamination for ANA detection by IIF according to ISO 15189 standards. ICARE offers a precious help for the accreditation of IIF qualitative methods. This innovative quantitative approach is in adequacy with the process of continuous improvement of the quality of clinical laboratories. Copyright © 2015 Elsevier B.V. All rights reserved.

Reconstructing the public in old and new governance: a Korean case of nuclear energy policy.

PubMed

Kim, Hyomin

2014-04-01

Korean nuclear energy regulatory policies started to change from earlier exclusively technocratic policies into open dialogues after several anti-nuclear protests in the 1990s. However, technocratic policies still coexist with the new regulatory orientation towards openness, participation and institutional accountability. This paper analyzes Korean nuclear regulatory policies since approximately 2005 as a blend of old and new governance. The aim of the paper is not to decide whether new nuclear governance is deliberative or not by completely reviewing Korean nuclear policies after the 2000s. Instead, it provides an empirical account of how seemingly more participatory processes in decision-making entail new problems while they work with and reproduce social assumptions of different groups of the public.

Relationship between schistosomiasis and arthropathy.

PubMed

Khalil, H M; Bebars, M A; el Okbi, L M; el Serougi, A O; Khalil, N M; el Tayeb, H; el Lamei, O; Tamara, F

1989-12-01

This study was carried out to suggest criteria for diagnosing arthritis associated with schistosomiasis. 180 cases were classified into three clinical groups, 120 schistosomal arthritic group (I), 20 schistosomal non-arthritic (II), 20 arthritic non-schistosomal (III) and 20 controls (IV). Four tests were done to exclude other causes of arthritis namely, Erythrocyte sedimentation rate (ESR), Rose-Waaler test (RW) for rheumatoid factor (RF), antinuclear antibody test (ANA) and determination of serum uric acid (SUA) level. A history, clinical examination, urine and stool examination, intradermal test (IDT), indirect haemagglutination test (IHAT), circumoval precipitin test (COPT) and complete blood picture, were performed for all groups. 20 patients were selected randomly from group I and received praziquantel to be followed up 6 months later. Bilharzial ova were found in the excreta of group I and II. The percentage of positive IDT, IHAT and COPT in I & II was 90.8%, 90%, 88.3% and 85% respectively. Blood picture showed mild anaemia and from low to moderate eosinophilia. ESR was moderately raised. RF positivity was 6.6%, 10%, 65% and 5% in the four groups respectively. ANA positivity was 1.6%, 0%, 50% and 0% respectively. There was a marked improvement of arthritic manifestations after praziquantel in 90% of cases.

Clinical and immunological characteristics of 150 systemic lupus erythematosus patients in Jamaica: a comparative analysis.

PubMed

Maloney, K C; Ferguson, T S; Stewart, H D; Myers, A A; De Ceulaer, K

2017-11-01

Background Epidemiological studies in systemic lupus erythematosus have been reported in the literature in many countries and ethnic groups. Although systemic lupus erythematosus in Jamaica has been described in the past, there has not been a detailed evaluation of systemic lupus erythematosus patients in urban Jamaica, a largely Afro-Caribbean population. The goal of this study was to describe the clinical features, particularly disease activity, damage index and immunological features, of 150 systemic lupus erythematosus subjects. Methods 150 adult patients (≥18 years) followed in rheumatology clinic at a tertiary rheumatology hospital centre (one of two of the major public referral centres in Jamaica) and the private rheumatology offices in urban Jamaica who fulfilled Systemic Lupus International Collaborating Clinics (SLICC) criteria were included. Data were collected by detailed clinical interview and examination and laboratory investigations. Hence demographics, SLICC criteria, immunological profile, systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) and SLICC/American College of Rheumatology (ACR) damage index (SDI) were documented. Results Of the 150 patients, 145 (96.7%) were female and five (3.3%) were male. The mean age at systemic lupus erythematosus onset was 33.2 ± 10.9. Mean disease duration was 11.3 ± 8.6 years. The most prevalent clinical SLICC criteria were musculoskeletal, with 141 (94%) of subjects experiencing arthralgia/arthritis, followed by mucocutaneous manifestations of alopecia 103 (68.7%) and malar rash 46 (30.7%), discoid rash 45 (30%) and photosensitivity 40 (26.7%). Lupus nephritis (biopsy proven) occurred in 42 (28%) subjects and 25 (16.7%) met SLICC diagnostic criteria with only positive antinuclear antibodies/dsDNA antibodies and lupus nephritis on renal biopsy. The most common laboratory SLICC criteria were positive antinuclear antibodies 136 (90.7%) followed by anti-dsDNA antibodies 95 (63.3%) and low complement (C3) levels 38 (25.3%). Twenty-seven (18%) met SLICC diagnostic criteria with only positive antinuclear antibodies/anti-dsDNA antibodies and lupus nephritis on renal biopsy. Mean SLEDAI score was 6.9 ± 5.1 with a range of 0-32. Organ damage occurred in 129 (86%) patients; mean SDI was 2.4 ± 1.8, with a range of 0-9. Conclusion These results are similar to the clinical manifestations reported in other Afro-Caribbean populations; however, distinct differences exist with respect to organ involvement and damage, particularly with respect to renal involvement, which appears to be reduced in our participants.

Changing Our Ways of Thinking: Health Professionals and Nuclear Weapons.

ERIC Educational Resources Information Center

Neal, Mary

1984-01-01

Outlines the issues raised by health professionals concerned about the threat of nuclear weapons and nuclear war, including epidemics, civil defense, arms costs, psychosocial aspects, and ethical responsibility. Appendixes include lists of antinuclear organizations, medical professional associations, and 160 references. (SK)

Autoimmune hepatitis related autoantibodies in children with type 1 diabetes

PubMed Central

2014-01-01

Background and objectives The frequency of Type 1 diabetes (T1D)-related autoantibodies was determined in children with autoimmune hepatitis. However, the incidence of autoimmune hepatitis related autoantibodies in children with T1D has been poorly investigated. The aim of the present cross sectional prospective study was to determine the occurrence of autoimmune hepatitis-related autoantibodies in children with T1D. Methods Children with T1D following in diabetic clinic in our center were screened for existence of liver related autoantibodies from November 2010 to November 2011. The patients’ sera were analyzed for the existence of autoantibodies such as anti-nuclear antibody, anti-smooth muscle antibody, and anti-Liver Kidney microsomal antibody, using enzyme linked immunoassay and indirect immunofluorescence methods. A titer of anti-nuclear antibody ≥1/40 was considered positive and titer of < 1/40 was considered negative. Anti-liver kidney microsomal antibody titer of < 3 U/ml was considered negative, 3 – 5 U/ml borderlines, and > 5 U/ml was considered positive. Results 106 children with T1D have been examined over a one-year period: age ranges between 8 months to 15.5 years, sixty two patients were females. Autoantibody screen revealed a girl with positive anti-liver kidney microsomal antibody (1%) and 8 children had positive anti-nuclear antibody (7.5%), without clinical, biochemical or radiologic evidence of liver disease. None of the patients had positive smooth muscle antibody. In conclusion Anti-liver kidney microsomal antibody is rarely found in sera of children with T1D; the clinical significance of which is unknown. PMID:24636465

Immunological disorders in chronic hepatitis C Egyptian patients.

PubMed

Shaker, M K; Fahmy, H M

1997-01-01

It is known that hepatitis C virus (HCV) related to chronic liver disease may be associated with various immunological disorders, among these disorders are mixed cryoglobulinemia, serum antinuclear antibodies, antismooth muscle antibodies and liver/kidney microsomal antibody type 1 (LKM1). However, the actual prevalence and pathogenic role of these disorders in patients with chronic hepatitis C are unclear. It was our aim to estimate the prevalence of different autoimmune antibodies in cases of hepatitis C chronic liver disease and to assess if such changes have any clinical significance. A total of 30 chronic hepatitis C patients (22 males and 8 females) with a mean age of 43.5 +/- 6.7 years, all patients were ELISA II positive, HCV RNA PCR positive and HbsAg negative, with elevated ALT more than 2 folds of the normal, in addition to 20 healthy controls of matched age and sex were tested for rheumatoid factor, cryoglobulin, antinuclear antibody, antismooth muscle antibody, antimitochondrial antibody and LKM1. The rheumatoid factor was present in 18 (60%) of the HCV Ab +ve patients and in 1 (5%) of the controls (p < 0.0002), cryoglobulins were present in 4 (13.3%) of the patients and not detected in the controls (p > 0.24), antinuclear antibody was positive in 4 (13.3%) of the patients and in 1 (5%) of the controls (p > 0.6), antismooth muscle antibody was positive in 1 (3.3%) of the patients and not detected in any of the controls, the antimitochondrial antibody and LKM1 were not detected in both the patients and the controls. In conclusion, we can see that chronic hepatitis C patients show prevalence of some autoimmune antibodies and their presence is not associated with any implication on the clinical presentation.

Anti-ENA antibody profiles in patients with hepatitis C virus infection.

PubMed

Litwin, Christine M; Rourk, Angela R

2018-03-01

The presence of antinuclear antibodies (ANA) has been described following hepatitis C virus (HCV). Very few studies have investigated the presence of anti-extractable nuclear antigens (ENA) in HCV infection. The aim of this study was to assess the prevalence of ENA antibodies in 100 patients with HCV infection compared to the prevalence of ENA antibodies in 100 healthy control patients. Sera from patients were tested for ENA using a multiplex microbead immunoassay. Sera positive for ENA were subsequently tested for ANA using an indirect immunofluorescence assay and titered if positive. Fourteen (14%) of the 100 patients with HCV infection had anti-ENA antibodies: four each showed anti-SSA antibodies and anti-dsDNA antibodies, three each had RNP antibodies and Scl-70 antibodies, and one each had anti-SSB, centromere B, Sm, and Sm/RNP antibodies. Ten of the 14 patients positive for anti-ENA were positive by indirect immunofluorescence staining (IFA) with titers ranging from 1:40 to 1:160. Five had antinuclear patterns, one had combined antinuclear and cytoplasmic patterns, and four only had a cytoplasmic pattern. Three of the 100 healthy control patients had ANA positive titers (1:80 and 1:320) and anti-ENA antibodies: one anti-Scl-70 and two anti-RNP. The prevalence of anti-ENA antibodies was significantly higher in the patients with HCV infections than in the healthy controls. Other studies of anti-ENA profiles in patients with HCV infection have identified similar patterns of positivity for anti-SSA, anti-SSB, anti-dsDNA, anti-RNP, anti- Sm/RNP, Scl-70, centromere B, and anti-Sm. © 2017 Wiley Periodicals, Inc.

Association between demyelinating disease and autoimmune rheumatic disease in a pediatric population.

PubMed

Amorim, Ana Luiza M; Cabral, Nadia C; Osaku, Fabiane M; Len, Claudio A; Oliveira, Enedina M L; Terreri, Maria Teresa

Multiple sclerosis (MS) and neuromyelitis optica (NMO) are demyelinating diseases of the central nervous system. Autoimmunity in patients with demyelinating disease and in their families has been broadly investigated and discussed. Recent studies show a higher incidence of rheumatic autoimmune diseases among adult patients with MS or NMO and their families, but there are no studies in the pediatric population. To evaluate an association of MS and NMO with autoimmune rheumatic diseases in pediatric patients. 22 patients younger than 21 years old with MS or NMO diagnosed before the age of 18 years were evaluated regarding epidemiological data, clinical presentation, association with autoimmune diseases, family history of autoimmune diseases, laboratory findings, imaging studies and presence of auto-antibodies. Among the patients studied, there was a prevalence of females (68.1%). The mean age of symptoms onset was 8 years and 9 months and the mean current age was 16 years and 4 months. Two patients (9%) had a history of associated autoimmune rheumatic disease: one case of juvenile dermatomyositis in a patient with NMO and another of systemic lupus erythematosus in a patient with MS. Three patients (13%) had a family history of autoimmunity in first-degree relatives. Antinuclear antibody was found positive in 80% of patients with NMO and 52% of patients with MS. About 15% of antinuclear antibody-positive patients were diagnosed with rheumatologic autoimmune diseases. Among patients with demyelinating diseases diagnosed in childhood included in this study there was a high frequency of antinuclear antibody positivity but a lower association with rheumatologic autoimmune diseases than that observed in studies conducted in adults. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

Detection of anti-nuclear antibody by immunofluorescence assay and enzyme immunoassay in childhood systemic lupus erythematosus: experience from Bangladesh.

PubMed

Dipti, Tanjeem Rabika; Azam, Mohammad Shaiful; Sattar, Mohammad Humayun; Rahman, Shahana Akhter

2012-02-01

Systemic lupus erythematosus (SLE) is a multisystem, chronic but often episodic, autoimmune disease that is characterized by the presence of antinuclear antibodies (ANA). The criteria set by American College of Rheumatology are widely used for diagnosis of SLE. Elevation of ANA titer is the most sensitive of the ACR criteria. There are different methods for detection of ANA. Indirect immunofluorescence (ANA-IFA) and enzyme immunoassay (ANA-EIA) are commonly used methods. The sensitivity of ANA-IFA using HEp-2 cell substrate is 90-100% in systemic rheumatic diseases. In Bangladesh most of the laboratories use ANA-EIA for detection of ANA. As the sensitivity of ANA-EIA is lower than ANA-IFA it might be that we are missing many cases of ANA positivity in childhood SLE cases. To detect ANA by immunofluorescence assay using HEp-2 cell substrate and enzyme immunoassay in childhood SLE and to compare the diagnostic performance of these methods. This is a cross-sectional analytical study. A total of 40 patients were enrolled. Among them 20 were childhood SLE cases. Another 20 patients of childhood rheumatic diseases other than SLE were taken as the disease control group. In childhood SLE cases, 100% were ANA-positive by IFA and 55% were ANA positive by EIA. The sensitivity of ANA-IFA was 100%. In contrast, sensitivity of ANA-EIA was 55%.   ANA-IFA is superior to ANA-EIA for detection of ANA in childhood SLE patients. ANA-IFA should be the primary screening test for children with clinical features suggestive of SLE. © 2011 The Authors. International Journal of Rheumatic Diseases © 2011 Asia Pacific League of Associations for Rheumatology and Blackwell Publishing Asia Pty Ltd.

People's Reactions to Nuclear War: Implications for Psychologists.

ERIC Educational Resources Information Center

Fiske, Susan T.

1987-01-01

Reviews available data documenting modal adults' beliefs, feelings, and actions regarding nuclear war. Examines discrepancies between peoples's beliefs and their relative lack of affective and behavioral response. Reviews data on possible psychological and social sources of those reactions. Contrasts average citizens, antinuclear activists, and…

Vulvovaginal-gingival Lichen Planus: Association with Lichen Planopilaris and Stratified Epithelium-specific Antinuclear Antibodies.

PubMed

Olszewska, Malgorzata; Banka-Wrona, Agnieszka; Skrok, Anna; Rakowska, Adriana; Górska, Renata; Solomon, Lynn W; Rudnicka, Lidia

2016-01-01

Vulvovaginal-gingival lichen planus (VVG-LP) consists of a triad of symptoms: vulval, vaginal and gingival lichen planus lesions. The aim of this study was to analyse the prevalence of lesions in various anatomical locations in patients with VVG-LP. The study included 126 consecutive patients with lichen planus. Sixteen (12.7%) patients fulfilled the criteria of VVG-LP. In 12/16 (75%) patients with VVG-LP scalp lesions were also observed. Stratified epithelium-specific antinuclear antibodies (SES-ANA) and anti-ΔNp.3α antibodies were detected in 10/16 (75%) patients with VVG-LP and in 15/110 (13.6%) patients with other forms of lichen planus (p < 0.05). In conclusion, VVG-LP is frequently associated with lichen planopilaris. The new entity may be termed "vulvovaginal-gingival-pilar lichen planus" and our study indicates that SES-ANA is a marker of this type of lichen planus with extensive, severe and refractory-to-therapy involvement of the mucous membranes, skin and scalp.

Anti-nuclear fantasies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Glynn, P.

1983-01-01

The author critiques two recent anti-nuclear books - Indefensible Weapons by two American professors, Robert Jay Lifton and Richard Falk; and Beyond the Cold War, a collection of polemical essays by E.P. Thompson, British Marxist historian. He sees a common thread in these books of moral rejection of traditional Western policies more than a rejection of the weapons themselves. Western institutions are judged indefensible in their arrangements for genocide. Glynn finds the authors focusing their criticism on the US, while excusing the Soviet Union, because of their alienation from US politics. He feels these are examples of a specialized literaturemore » movement that lacks a clear vision of the new order it promotes, however, because it is wary of all political arrangements. Attacks on the free press and American foreign policy take on an Orwellian irony in their rejection of security facts and their emphasis on psychological ills. Criticism of this approach does not deny the threat of nuclear weapons when it points out that, so far, the political approach has prevented their use. (DCK)« less

Antinuclear autoantibodies and pregnancy outcome in women with unexplained recurrent miscarriage.

PubMed

Ticconi, Carlo; Pietropolli, Adalgisa; Borelli, Barbara; Bruno, Valentina; Piccione, Emilio; Bernardini, Sergio; Di Simone, Nicoletta

2016-11-01

To investigate whether antinuclear autoantibodies (ANA) could be related to the outcome of the successive pregnancy in women with unexplained recurrent miscarriage (uRM). Circulating ANA were measured by indirect immunofluorescence in 86 women with uRM before pregnancy, repeated in the first trimester of the successive gestation and correlated with pregnancy outcome. Forty-one women were ANA- and 45 were ANA+ before pregnancy. No relation was found between pre-pregnancy ANA status and the outcome of the successive pregnancy. However, when these women were monitored at 7th week during their pregnancy for ANA, of the 22 ANA+ women who remained ANA+ seven miscarriages (31.8%) were observed, whereas all of the 23 ANA+ women who became ANA- had pregnancies ongoing beyond the 20th week without miscarriage. ANA status could have a role in uRM. Disappearance of ANA in early pregnancy could have a favorable prognostic value in the successive pregnancy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Fluorescence intensity positivity classification of Hep-2 cells images using fuzzy logic

NASA Astrophysics Data System (ADS)

Sazali, Dayang Farzana Abang; Janier, Josefina Barnachea; May, Zazilah Bt.

2014-10-01

Indirect Immunofluorescence (IIF) is a good standard used for antinuclear autoantibody (ANA) test using Hep-2 cells to determine specific diseases. Different classifier algorithm methods have been proposed in previous works however, there still no valid set as a standard to classify the fluorescence intensity. This paper presents the use of fuzzy logic to classify the fluorescence intensity and to determine the positivity of the Hep-2 cell serum samples. The fuzzy algorithm involves the image pre-processing by filtering the noises and smoothen the image, converting the red, green and blue (RGB) color space of images to luminosity layer, chromaticity layer "a" and "b" (LAB) color space where the mean value of the lightness and chromaticity layer "a" was extracted and classified by using fuzzy logic algorithm based on the standard score ranges of antinuclear autoantibody (ANA) fluorescence intensity. Using 100 data sets of positive and intermediate fluorescence intensity for testing the performance measurements, the fuzzy logic obtained an accuracy of intermediate and positive class as 85% and 87% respectively.

Nuclear power: renaissance or relapse? Global climate change and long-term Three Mile Island activists' narratives.

PubMed

Culley, Marci R; Angelique, Holly

2010-06-01

Community narratives are increasingly important as people move towards an ecologically sustainable society. Global climate change is a multi-faceted problem with multiple stakeholders. The voices of affected communities must be heard as we make decisions of global significance. We document the narratives of long-term anti-nuclear activists near the Three Mile Island (TMI) nuclear power plant who speak out in the dawn of a nuclear renaissance/relapse. While nuclear power is marketed as a "green" solution to global warming, their narratives reveal three areas for consideration; (1) significant problems with nuclear technology, (2) lessons "not" learned from the TMI disaster, and (3) hopes for a sustainable future. Nuclear waste, untrustworthy officials and economic issues were among the problems cited. Deceptive shaping of public opinion, nuclear illiteracy, and an aging anti-nuclear movement were reasons cited for the lessons not learned. However, many remain optimistic and envision increased participation to create an ecologically-balanced world.

Lack of antinuclear antibody in children with atopic dermatitis.

PubMed

Dhar, S; Kanwar, A J; Deodhar, S D

1997-01-01

Antinuclear antibody (ANA) was assayed in 76 children with atopic dermatitis (AD) of which 46 were males and 30 females. Their ages ranged from 6 months to 12 years (mean 3.4 years). Age at onset of AD ranged from 2 months to 5.5 years (mean 1.9 years) and its duration ranged from 4 months to 4 years (mean 1.2 years). While facial lesions were present in 56 (73.3%) patients, 49 (64.5%) patients had predominant involvement of extensors. As per severity score designed by Rajka and Langerland, 31 (40.8%), 42 (55.3%) and 3 (3.9%) patients had mild, moderate and severe diseases respectively. History of photosensitivity was present in 6 (7.9%) patients. Serum samples were positive for ANA in a very low titre (1:20) in 2/6 patients with facial lesions. However LE cell, rheumatoid factor and C-reactive proteins were negative and serum complement levels were within normal limits.

Autoantibodies and their clinical significance in a black vitiligo population.

PubMed

Grimes, P E; Halder, R M; Jones, C; Chakrabarti, S G; Enterline, J; Minus, H R; Kenney, J A

1983-04-01

The frequency of autoantibodies was determined in 70 black vitiligo patients and controls. Both groups were screened for antithyroid, antinuclear, antigastric parietal cell, anti-smooth muscle cell, and antimitochondrial autoantibodies. The significance of autoantibodies was determined in vitiligo patients by correlating their presence or absence with various clinical features of the patients. The overall frequencies of autoimmune and endocrine diseases were also assessed in vitiligo patients, controls, and their respective families. Vitiligo patients had an increased frequency of antithyroid antibodies and an increased frequency of autoimmune and/or endocrine diseases. These diseases included, especially, hyperthyroidism, hypothyroidism, and alopecia areata. Autoantibody-positive vitiligo patients had an increased frequency of first- and second-degree relatives having autoimmune and/or endocrine diseases. These findings tend to support an autoimmune cause of vitiligo in black patients.

Effects of Libby amphibole exposure on the development of autoimmunity in the rat

EPA Science Inventory

Epidemiological data suggest that exposure to the amphibole-containing vermiculite in Libby, MT was associated with increased risk (odds ratio of 2.14) for developing systemic autoimmune diseases (SAID). Elevated titers of antinuclear antibodies (ANA) were also found in Libby res...

The Nuclear Power/Nuclear Weapons Connection.

ERIC Educational Resources Information Center

Totten, Sam; Totten, Martha Wescoat

1985-01-01

Once they have nuclear power, most countries will divert nuclear materials from commercial to military programs. In excerpts from the book "Facing the Danger" (by Totten, S. and M. W., Crossing Press, 1984), five anti-nuclear activists explain how and why they have been addressing the nuclear connection. (RM)

Serodiagnosis and immune profile in rheumatoid arthritis.

PubMed

Chakraborty, P; Bhattacharya, S; Chakraborty, M; Pal, B

1997-11-01

One hundred and seventy-five cases of clinically diagnosed rheumatoid arthritis, 82 non-rheumatoid cases suffering from various other diseases and 40 healthy normal controls were investigated for detection of rheumatoid factor, quantitation of serum immunoglobulin, demonstration of antinuclear antibody (ANA) and LE cell phenomenon. Microlatex agglutination test of serum for rheumatoid factor (RF) showed 64% positivity in rheumatoid group and 1.2% positivity in non-rheumatoid group. All three immunoglobulins (IgG, IgM, IgA) were found to be raised in serum of patients with rheumatoid arthritis, whereas only IgA level was elevated in serum of patients with non-rheumatoid diseases. ANA and LE cell phenomenon were observed in 3.4% and 2.8% cases respectively in cases of clinically diagnosed rheumatoid arthritis who had been suffering from severe active rheumatoid arthritis. In non-rheumatoid group RF was positive in significant titre in only one case of leprosy. Synovial fluid and synovium were found to be heavily infiltrated by plasma cells and lymphocytes. RF appears first in synovial fluid and then in serum. Hence RF titre in blood may not attain significant level for the first several months.

Idiopathic Inflammatory Myopathies

PubMed Central

Dimachkie, Mazen M.; Barohn, Richard J.

2012-01-01

The idiopathic inflammatory myopathies are a group of rare disorders including polymyositis (PM), dermatomyositis (DM), and autoimmune necrotizing myopathies (NMs). The idiopathic inflammatory myopathies share many similarities. They present acutely, subacutely, or chronically with marked proximal and symmetric muscle weakness, except for associated distal and asymmetric weakness in inclusion body myositis. The idiopathic inflammatory myopathies also share a variable degree of creatine kinase (CK) elevation and a nonspecifically abnormal electromyogram demonstrating an irritative myopathy. The muscle pathology demonstrates inflammatory exudates of variable distribution within the muscle fascicle. Despite these similarities, the idiopathic inflammatory myopathies are a heterogeneous group. The overlap syndrome (OS) refers to the association of PM, DM, or NM with connective tissue disease, such as scleroderma or systemic lupus erythematosus. In addition to elevated antinuclear antibodies (ANA), patients with OS may be weaker in the proximal arms than the legs mimicking the pattern seen in some muscular dystrophies. In this review, we focus on DM, PM, and NM and examine current and promising therapies. PMID:23117947

Science and Public Policy since World War II.

ERIC Educational Resources Information Center

Rossiter, Margaret W.

1985-01-01

Discusses: material/personnel shortages and surpluses around 1950; federal aid to nonmilitary research; loyalty oaths and security checks; rise of the behavioral sciences; science education, from the Cold War to creationism; antinuclear protests and the limited test ban treaty, 1954-1963; Sputnik and the space program; and health, safety, and…

Discovery of Antinuclear Antibodies in Pigs Infected with Porcine Circovirus Type 2

USDA-ARS?s Scientific Manuscript database

Introduction. Porcine circovirus type 2 (PCV2) causes post-weaning-multisystemic-wasting-syndrome (PMWS), a swine disease first observed in Canada in 1991 (1). It is characterized by general wasting, respiratory disease, jaundice and pallor in young pigs resulting in production losses and variable...

Energy politics

NASA Astrophysics Data System (ADS)

McEvoy, Augustin

2012-07-01

In his review of Tyler Hamilton's book Mad Like Tesla (May pp44-45), Roger Bridgman writes that "in energy supply, obviously, companies cannot simply junk huge infrastructure investments in favour of something new, however good it might be". But that is exactly what Angela Merkel's administration has done in Germany with its anti-nuclear policy.

Anti-Nuclear Attitudes in New Zealand and Australia,

DTIC Science & Technology

1985-12-01

Wellington, 5 March 1985. 5. John Henderson, Keith Jackson , Richard Kennawav, eds. Beyond New Zealand; The Foreign Policy of a Small State. (Auckland...the city of San Francisco this first day of September, 1951. For Australia: PERCY C. SPENDER For New Zealand: C.A. BERENDSEN For the United States of

The Limits of Empowerment in Anti-Nuclear Advocacy: A Case Study of Adult Education for Technological Literacy.

ERIC Educational Resources Information Center

Regnier, Robert; Penna, Phillip

1996-01-01

Using a theory of technological literacy, analysis of a project to oppose uranium mining in Saskatchewan revealed how the potential for empowerment is often overstated. Informing citizens to participate in critical discourse does not always lead to decisions reflecting their interests. (SK)

Government: Nuclear Safety in Doubt a Year after Accident.

ERIC Educational Resources Information Center

Ember, Lois R.

1980-01-01

A year after the accident at Three Mile Island (TMI), the signals transmitted to the public are still confused. Industry says that nuclear power is safe and that the aftermath of TMI ushers in a new era of safety. Antinuclear activists say TMI sounded nuclear power's death knell. (Author/RE)

Nuclear Bashing in Chernobyl Coverage: Fact or Fiction?

ERIC Educational Resources Information Center

Friedman, Sharon M.; And Others

Critics of coverage of nuclear power have charged that the media overemphasize the importance of nuclear accidents, encourage public fear, and omit information vital to public understanding of nuclear power and risk. Some also feel there is an anti-nuclear bias among reporters and editors. A study was conducted to determine if such charges were…

Public Discussion of Nuclear Warfare: A Time for Hope.

ERIC Educational Resources Information Center

Cooper, Martha

Anti-nuclear discourse, which peaked in 1981-82, signaled an emergence of public discourse on the nuclear warfare issue. During the development of the original atomic bomb, public discussion of the issue was severely restricted, but immediately after the bombing of Hiroshima and Nagasaki, discourse on the subject increased. During the Cold War…

Development of antinuclear antibodies and a genetic linkage in pigs infected with porcine circovirus type 2

USDA-ARS?s Scientific Manuscript database

Objectives. Prominent nuclear immunohistochemical staining of a PCV-2 free porcine kidney cell line (PK-15) was detected with a rabbit polyclonal antibody produced against a conserved PCV2 Rep-protein peptide. This unexpected finding led us to retrospectively test sera from gnotobiotic pigs for the ...

Late results of the Royal Free Hospital prospective controlled trial of prednisolone therapy in hepatitis B surface antigen negative chronic active hepatitis.

PubMed Central

Kirk, A P; Jain, S; Pocock, S; Thomas, H C; Sherlock, S

1980-01-01

A long-term follow-up of at least 10 years or until death of 44 patients taking part in a controlled prospective trial of prednisolone therapy in hepatitis B antigen negative chronic active hepatitis (lupoid hepatitis) has been performed at the Royal Free Hospital, London. Patients presenting between 1963 and 1967 were randomly allocated into control and treatment groups. Ten year life table survival curves showed a significantly improved survival in the treatment group where 63% of patients were alive at 10 years compared with only 27% in the control group (log rank test, P = 0.03). The median survival in the treatment group was 12.2 years compared with 3.3 years in the control group. The mean duration of treatment was 4.5 years. Age, presence of antinuclear factor, cirrhosis, or level of serum transaminases at presentation did not appear to affect survival. Male patients if untreated had a poorer prognosis than females (P = 0.02). The natural history of chronic active hepatitis appeared from clinical, biochemical, and histological findings to be from an active hepatitis or cirrhosis to inactive macronodular cirrhosis. Prednisolone therapy significantly improved survival by reducing mortality in the early active phase of the disease. PMID:6988304

Autoimmune response of IgE antibodies to cellular self-antigens in systemic Lupus Erythematosus.

PubMed

Atta, Ajax Mercês; Santiago, Mittermayer Barreto; Guerra, Fernanda Garcia; Pereira, Mariana Menezes; Sousa Atta, Maria Luiza B

2010-01-01

Systemic lupus erythematosus (SLE) patients may exhibit high total IgE and antinuclear IgE antibodies (ANA-IgE). Here, we investigated the specificity of ANA-IgE in SLE patients and the involvement of cytokines in this immune response. Sera from 92 SLE patients and 68 healthy controls were evaluated for the presence of antinuclear IgE antibodies by immunoperoxidase with HEp-2,000(R) cells and immunoblotting with IgG-depleted sera. Total IgE, IgE specific to allergens, and serum cytokine levels were determined by ELISA. Antinuclear IgE antibodies were detected only in SLE patients (29/92, 31.5%). High total IgE was associated with ANA-IgE (p < 0.0001), but was not associated with IgE antibodies to allergens. In the immunoblotting, ANA-IgE reacted with nucleosomes (23/29, 79.3%), dsDNA (14/29, 48.3%), SS-A/Ro (14/29, 48.3%), SS-B/La (2/29, 18.7%), Sm (14/29, 48.3%) and RNP (18/29, 62.1%). Patients with ANA-IgE had very low serum IL-4, less IL-5 than controls (p < 0.05), more IL-10 than seronegative patients (p < 0.05), and unaltered IFN-gamma levels. The IL-5/IL-10 ratio was lower in ANA-IgE seropositive patients in comparison with either seronegative patients (p < 0.05) or healthy controls (p = 0.001). Controls displayed higher IL-5/IFN-gamma ratios than either SLE patients with ANA-IgE (p < 0.05) or patients without these immunoglobulins (p < 0.01). We conclude that IgE antibodies against cell autoantigens involved in protein expression, cellular proliferation, and cell death are present in patients with SLE. Interleukin-10 seems to down-regulate this IgE autoimmune response in SLE. Copyright 2010 S. Karger AG, Basel.

Associations Between Selected Xenobiotics and Antinuclear Antibodies in the National Health and Nutrition Examination Survey, 1999-2004.

PubMed

Dinse, Gregg E; Jusko, Todd A; Whitt, Irene Z; Co, Caroll A; Parks, Christine G; Satoh, Minoru; Chan, Edward K L; Rose, Kathryn M; Walker, Nigel J; Birnbaum, Linda S; Zeldin, Darryl C; Weinberg, Clarice R; Miller, Frederick W

2016-04-01

Potential associations between background environmental chemical exposures and autoimmunity are understudied. Our exploratory study investigated exposure to individual environmental chemicals and selected mixtures in relation to the presence of antinuclear antibodies (ANA), a widely used biomarker of autoimmunity, in a representative sample of the U.S. This cross-sectional analysis used data on 4,340 participants from the National Health and Nutrition Examination Survey (1999-2004), of whom 14% were ANA positive, to explore associations between ANA and concentrations of dioxins, dibenzofurans, polychlorinated biphenyls, organochlorines, organophosphates, phenols, metals, and other environmental exposures and metabolites measured in participants' serum, whole blood, or urine. For dioxin-like compounds with toxic equivalency factors, we developed and applied a new statistical approach to study selected mixtures. Lognormal models and censored-data methods produced estimates of chemical associations with ANA in males, nulliparous females, and parous females; these estimates were adjusted for confounders and accommodated concentrations below detectable levels. Several associations between chemical concentration and ANA positivity were observed, but only the association in males exposed to triclosan remained statistically significant after correcting for multiple comparisons (mean concentration ratio = 2.8; 95% CI: 1.8, 4.5; p < 0.00001). These data suggest that background levels of most xenobiotic exposures typical in the U.S. population are not strongly associated with ANA. Future studies should ideally reduce exposure misclassification by including prospective measurement of the chemicals of concern and should track changes in ANA and other autoantibodies over time. Dinse GE, Jusko TA, Whitt IZ, Co CA, Parks CG, Satoh M, Chan EKL, Rose KM, Walker NJ, Birnbaum LS, Zeldin DC, Weinberg CR, Miller FW. 2016. Associations between selected xenobiotics and antinuclear antibodies in the National Health and Nutrition Examination Survey, 1999-2004. Environ Health Perspect 124:426-436; http://dx.doi.org/10.1289/ehp.1409345.

An Atlas of Nuclear Energy. A Non-Technical World Portrait of Commercial Nuclear Energy.

ERIC Educational Resources Information Center

Ball, John M.

This atlas is a nontechnical presentation of the geography and history of world commercial nuclear power with particular emphasis on the United States. Neither pro- nor antinuclear, it presents commercial nuclear power data in a series of specially prepared, easily read maps, tables, and text. The first section (United States) includes information…

Energy & Climate: Getting Quantitative

NASA Astrophysics Data System (ADS)

Wolfson, Richard

2011-11-01

A noted environmentalist claims that buying an SUV instead of a regular car is energetically equivalent to leaving your refrigerator door open for seven years. A fossil-fuel apologist argues that solar energy is a pie-in-the-sky dream promulgated by na"ive environmentalists, because there's nowhere near enough solar energy to meet humankind's energy demand. A group advocating shutdown of the Vermont Yankee nuclear plant claims that 70% of its electrical energy is lost in transmission lines. Around the world, thousands agitate for climate action, under the numerical banner ``350.'' Neither the environmentalist, the fossil-fuel apologist, the antinuclear activists, nor most of those marching under the ``350'' banner can back up their assertions with quantitative arguments. Yet questions about energy and its environmental impacts almost always require quantitative answers. Physics can help! This poster gives some cogent examples, based on the newly published 2^nd edition of the author's textbook Energy, Environment, and Climate.

An 11-year and 10-month-old girl with purpura and chest pain.

PubMed

Chen, Pei-Hsuan; Chiang, Bor-Luen; Lu, Meng-Yao; Yang, Yao-Hsu

2014-10-01

Mucosa-associated lymphoid tissue lymphoma (MALToma) is a type of B-cell lymphoma. Case reports of childhood thymic MALToma and its association with vasculitis are rarely found in the related literature. Herein, we present a report of an 11-year and 10-month-old girl who was initially diagnosed with cutaneous vasculitis characterized by nonthrombocytopenic palpable purpura, positive antinuclear antibody and anti-SSA (Ro) antibody. Eight months later, a thymic mediastinal mass was found. Surgical excision was performed and results of pathological analysis revealed an extranodal marginal zone CD20(+) B-cell MALToma. Benign response to the chemotherapeutic regimen of Berlin-Frankfurt-Münster group NHL-BFM 90 R2 without relapse was noted in 2 years of follow-up. For the first time, our case demonstrated some clinical evidence of the association between vasculitis and childhood MALToma. Copyright © 2012. Published by Elsevier B.V.

Necrotizing granulomatous inflammation of the glans penis.

PubMed

Christodoulidou, Michelle; Bunker, Christopher B; Trevisan, Giorgia; Muneer, Asif

2016-08-24

We describe the case of a 73-year-old man who presented with a 10-month history of an ulcerating lesion on the glans penis. Initially this was thought to be an invasive squamous cell carcinoma but a biopsy showed histological features consistent with necrotizing granulomatous inflammation. Extensive serological, immunological and microbiological tests only showed a positive antinuclear and perinuclear antineutrophil cytoplasmic antibodies indicating a possible autoimmune aetiology but an underlying systemic cause was not identified. Treatment with oral corticosteroids limited the inflammatory process but due to the gross destruction of the glans penis, he still required a glansectomy and split-skin graft reconstruction from which he recovered well. Although this patient ultimately required surgery for this rare presentation, this case highlights the differential diagnosis of penile ulceration (that transcends neoplasia) and the importance of performing and interpreting penile biopsies before undertaking potentially mutilating definitive surgery. 2016 BMJ Publishing Group Ltd.

Granisetron and carvedilol can protect experimental rats againstadjuvant-induced arthritis.

PubMed

Ahmed, Yasmin Moustafa; Messiha, Basim Anwar Shehata; Abo-Saif, Ali Ahmed

2017-04-01

Rheumatoid arthritis (RA), a disabling autoimmune disorder of the joints as well as other organs, affects about 1% of population. Unfortunately, all current treatments of RA cause severe gastrointestinal, renal and other complications. We aimed to evaluate the possible antiarthritic effects of a serotonin 5-HT 3 receptor blocker, granisetron, and a nonselective adrenergic receptor blocker, carvedilol, on complete Freund's adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving granisetron (2.5 mg/kg/day) and carvedilol (10 mg/kg/day). Serum-specific rheumatoid, immunological, inflammatory and oxidative stress biomarkers were assessed. A confirmatory histopathological study on joints and spleens was performed. Granisetron administration significantly improved all the measured biomarkers, with the values of rheumatoid factor, matrix metalloproteinase-3, cartilage oligomeric matrix protein, immunoglobulin G, antinuclear antibody and myeloperoxidase being restored back to normal levels. Carvedilol administration significantly improved all biomarkers, with serum MPO value restored back to normal levels. Serotonin 5-HT 3 receptor blockers and adrenergic receptor blockers, represented by granisetron and carvedilol, may represent new promising protective strategies against RA, at least owing to immune-modulator, anti-inflammatory and antioxidant potentials.

Diagnosis and Management of Paediatric Autoimmune Liver Disease: ESPGHAN Hepatology Committee Position Statement.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego; Baumann, Ulrich; Czubkowski, Piotr; Debray, Dominique; Dezsofi, Antal; Fischler, Björn; Gupte, Girish; Hierro, Loreto; Indolfi, Giuseppe; Jahnel, Jörg; Smets, Françoise; Verkade, Henkjan J; Hadzic, Nedim

2017-11-03

Paediatric autoimmune liver disease is characterised by inflammatory liver histology, circulating autoantibodies and increased levels of IgG, in the absence of a known etiology. Three conditions have a likely autoimmune pathogenesis: autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. Two types of paediatric AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, AIH-1) or liver kidney microsomal type 1 and/or anti-liver cytosol type 1 antibodies (anti-LKM-1/anti-LC-1; AIH-2).Pertinent issues addressing the diagnosis, treatment and long term follow up were formulated by a core group of ESPGHAN members. They have commissioned the first authors with execution of this project. Initially, they have performed a systematic literature search on MEDLINE, ResearchGate and Mendeley databases over the last 30 years and produced a document focusing on prospective and retrospective studies in children. The ESPGHAN core group and ESPGHAN Hepatology Committee members voted on each recommendation, using a formal voting technique.

Effects of a didactic and guided-imagery intervention regarding horrendous death by nuclear war upon fear of death, health locus of control, and social responsibility in health education college students

DOE Office of Scientific and Technical Information (OSTI.GOV)

Campanelli, L.C.

1987-01-01

This investigation studied the effects of a videotaped lecture explaining horrendous death theory, with a guided imagery component describing horrendous death of a beloved other, upon action toward anti-nuclearism and three individual difference variables. The primary purpose of this study was to determine the effects of a videotaped lecture on college students' fear of death, health locus of control, and social responsibility. A second purpose was to determine whether participants who viewed the videotape were likely to sign a petition against nuclear war, in support of the Physicians for Social Responsibility's position against nuclearism. One hundred fifty-two (152) college studentsmore » participated in this study; approximately 55% were female and 50% were seniors. No significant differences were found regarding individual difference variables, except concerning fear of death of self between death education and non-death education experimental groups. Although an interaction effect was found, the hypothesis that experimental groups would be more likely to sign the petition against nuclear was not confirmed.« less

A Spectre Haunting: New Dimensions of Youth Protest in Western Europe. Occasional Paper 8208.

ERIC Educational Resources Information Center

Mushaben, Joyce Marie

European protest movements of the eighties are analyzed and compared to the dissident movements of the sixties and seventies. The focus is on the peace, anti-nuclear, and ecology movements, the drive for autonomous youth centers in Switzerland, racial disturbances in Britain, and unrest among the urban squatters in the German Federal Republic. Six…

Preclinical Validation of Anti-Nuclear Factor Kappa B Therapy against Vestibular Schwannoma and Neurofibromatosis Type II

DTIC Science & Technology

2015-06-01

This dose is less than the range of salicylate toxicity, with milder symptoms such as tinnitus being noted ate; PTG, prostaglandin; qPCR...Jordan MT, Chan SB, Wahl MS, Rubin RL. Tinnitus as a measure of salicylate toxicity in the overdose setting. West J Emerg Med 2008;9:146–9. 26. Myers EN

The prevalence of antinuclear antibodies in patients with apparent polymorphic light eruption.

PubMed

Murphy, G M; Hawk, J L

1991-11-01

Polymorphic light eruption (PLE) is a very common photosensitive disorder, the most important differential diagnosis of which is lupus erythematosus (LE). One-hundred and forty-two patients with PLE were screened for circulating antinuclear (ANA), Ro and La antibodies over a 2-year period. Results were negative in 66 patients. Sixty-two patients had low-titre ANA of various patterns, ranging from trace to 1/80 without evidence of LE although one later developed subacute cutaneous LE. Fourteen had more significant findings, six with ANA ranging from 1/160 to 1/1280 but no anti-Ro antibodies, four with ANA ranging from 1/160 to 1/1280 and also with anti-Ro antibodies and four patients with anti-Ro antibodies but low-titre ANA, one of whom later developed discoid LE. Three of these 14 patients fulfilled the American Rheumatism Association criteria for the diagnosis of systemic LE, but it was not certain in any of the patients whether the PLE-like rash represented cutaneous LE or coincidental PLE. However the overall 10% incidence of definite or possible LE in patients with suspected PLE suggests that all PLE patients should be screened for LE.

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity

PubMed Central

Fouad, Hanan; El Raziky, Maissa; Hassan, Eman Medhat; Aziz, Ghada Mahmoud Abdel; Darweesh, Samar K; Sayed, Ahmed Reda

2016-01-01

AIM To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response. PMID:27843539

Comparison of Behavioral Treatments for Raynaud’s Disease,

DTIC Science & Technology

1984-01-01

biofeedback with other treatment modes (6, 9-10). Hypnosis and relaxation have also received attention as treatments for vasoconstrictive syndromes (11). Surwit...sedimentation rate, antinuclear antibody, and serum glucose levels. All test results were within normal limits. Instrumentation : The temperature reponse...manufactured by the Yellow Springs Instrument Co., Yellow Springs, OH. 3. Thermal feedback was provided by an Autogen 1000b feedback thermometer, and

Missile’s Guidance Head Anti-Nuclear Electromagnetic Pulse Reinforcement,

DTIC Science & Technology

1996-11-18

electromagnetic pulse bomb is one of them. This kind of nuclear bomb is mainly used to interfere or damage un-reinforced electric and electronic... electromagnetic pulse , the damaging mechanism of the nuclear electromagnetic pulse to the guidance head, and the response of electronic devices to...the nuclear electromagnetic pulse , at last introduces the guidance heads defense method to the nuclear electromagnetic pulse .

The Probabilities of Unique Events

DTIC Science & Technology

2012-08-30

social justice and also participated in antinuclear demonstrations. The participants ranked the probability that Linda is a feminist bank teller as...investigated them. We propose a new theory (implemented in a computer program) in which such estimates depend on an intuitive non-numerical system capable only...of simple procedures, and a deliberative system that maps intuitions into numbers. The theory predicts that estimates of the probabilities of

Incidence of autoantibodies in the infertile population.

PubMed

Cubillos, J; Lucena, A; Lucena, C; Mendoza, J C; Ruiz, H; Arango, A; Quiroga, G; Ferro, J; Lucena, E

1997-06-01

The purpose of this study was to determine the incidence of autoantibodies in patients with no term pregnancies. Patients selected included 43 with primary infertility and 110 with a history of pregnancy loss. In the first group the incidence of antinuclear antibodies (ANA) and IgG and IgM antiphospholipid antibodies (APL) was 37.2% (p < 0.05) and 53.5% (p < 0.05), respectively. In the group of patients with a history of miscarriage, 31.8% (p < 0.05) were positive for ANA and 38.2% (p < 0.05) for APL. Controls were 35 healthy patients with proven fertility and no history of pregnancy loss or autoimmune disease. In this group the incidence of ANA was 5.7% and 11.4% for APL. The high incidence of autoantibodies found in patients with primary infertility might suggest a direct involvement of these antibodies in reproductive failure and consequently in IVF and assisted fertility procedures. The prevalence of ANA and APL has been extensively described in patients with a history of recurrent pregnancy losses (RPL). In this study we observed antibodies even after the first miscarriage. We therefore conclude that patients with a history of reproductive failure should be immunologically evaluated and treated before undergoing assisted fertilization techniques or before a new pregnancy in those cases of RPL.

Identification of New Potential Scientific and Technology Areas for DoD Application. Summary of Activities

DTIC Science & Technology

1986-07-31

designer will be able to more rapid- ly assemble a total software package from perfected modules that can be easily de - bugged or replaced with more...antinuclear interactions e. gravitational effects of antimatter 2. possible machine parameters and lattice design 3. electron and stochastic cooling needs 4...implementation, reliability requirements; development of design environments and of experimental methodology; technology transfer methods from

Male-only systemic lupus.

PubMed

Aggarwal, Rachna; Namjou, Bahram; Li, Shibo; D'Souza, Anil; Tsao, Betty P; Bruner, Benjamin F; James, Judith A; Scofield, R Hal

2010-07-01

Systemic lupus erythematosus (SLE) is more common among women than men, a ratio of about 10 to 1. We undertook this study to describe familial male SLE within a large familial SLE cohort. SLE families (2 or more patients) were identified from the Lupus Multiplex Registry and Repository. Genomic DNA and blood samples were obtained using standard methods. Autoantibodies were determined by multiple methods. Medical records were abstracted for SLE clinical data. Fluorescent in situ hybridization (FISH) was performed with X and Y centromere-specific probes, and a probe specific for the Toll-like receptor 7 gene on the X chromosome. Among 523 SLE families, we found 5 families in which all the SLE patients were male. FISH found no yaa gene equivalent in these families. SLE-unaffected primary female relatives from the 5 families with only-male SLE patients had a statistically increased rate of positive antinuclear antibodies compared to SLE-unaffected female relatives in other families. White men with SLE were 5 times more likely to have an offspring with SLE than White women with SLE, but there was no difference in this likelihood among Black men. Because women in the all-male families had positive antinuclear antibodies, and men are more likely to have children with SLE, these data suggest genetic susceptibility factors that act only in men.

Autoantibodies and their Judicious Use in Pediatric Rheumatology Practice.

PubMed

Saikia, Biman; Rawat, Amit; Vignesh, Pandiarajan

2016-01-01

Autoantibody testing forms an important part of diagnostic workup of patients in Pediatric rheumatology practice. However it is important to understand that the mere presence of autoantibodies does not necessarily mean the presence of an underlying autoimmune disease. Autoantibodies may be present decades before the development of clinical manifestations of an autoimmune disease and may be viewed as harbingers of Autoimmune disease. On the other hand, low-affinity autoantibodies may be present in normal healthy individuals; these natural autoantibodies serve an important function in immune regulation and tolerance. Autoantibody testing in pediatric practice mainly includes testing for anti-nuclear antibodies, anti-dsDNA antibodies, anti-neutrophil cytoplasmic autoantibodies and antiphospholipid antibodies. Rheumatoid factor and anti-CCP do not have much significance in the diagnostic schema in pediatric rheumatology, except perhaps for classification of juvenile idiopathic arthritis (JIA) and prognostication in late-onset polyarticular JIA. The positive predictive value (PPV) of any laboratory test depends on the prevalence of the disease in the population being tested. Hence, test ordering practices greatly impact the performance characteristics and positive predictive value of any laboratory test. A restricted test ordering only in patients with clinical signs and symptoms suggestive of autoimmune disease would thus greatly increase the PPV of tests such as antinuclear antibody used for diagnosing autoimmunity.

Automated indirect immunofluorescence evaluation of antinuclear autoantibodies on HEp-2 cells.

PubMed

Voigt, Jörn; Krause, Christopher; Rohwäder, Edda; Saschenbrecker, Sandra; Hahn, Melanie; Danckwardt, Maick; Feirer, Christian; Ens, Konstantin; Fechner, Kai; Barth, Erhardt; Martinetz, Thomas; Stöcker, Winfried

2012-01-01

Indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA). However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the EUROPattern Suite has been developed as a comprehensive automated processing and interpretation system for standardized and efficient ANA detection by HEp-2 cell-based IIF. In this study, the automated pattern recognition was compared to conventional visual interpretation in a total of 351 sera. In the discrimination of positive from negative samples, concordant results between visual and automated evaluation were obtained for 349 sera (99.4%, kappa = 0.984). The system missed out none of the 272 antibody-positive samples and identified 77 out of 79 visually negative samples (analytical sensitivity/specificity: 100%/97.5%). Moreover, 94.0% of all main antibody patterns were recognized correctly by the software. Owing to its performance characteristics, EUROPattern enables fast, objective, and economic IIF ANA analysis and has the potential to reduce intra- and interlaboratory variability.

A paperless autoimmunity laboratory: myth or reality?

PubMed

Lutteri, Laurence; Dierge, Laurine; Pesser, Martine; Watrin, Pascale; Cavalier, Etienne

2016-08-01

Testing for antinuclear antibodies is the most frequently prescribed analysis for the diagnosis of rheumatic diseases. Indirect immunofluorescence remains the gold standard method for their detection despite the increasing use of alternative techniques. In order to standardize the manual microscopy reading, automated acquisition and interpretation systems have emerged. This publication enables us to present our method of interpretation and characterization of antinuclear antibodies based on a cascade of analyses and to share our everyday experience of the G Sight from Menarini. The positive/negative discrimination on Hep cells 2000 is correct in 85% of the cases. In most of the false negative results, it is a question of aspecific or low titers patterns, but a few cases of SSA speckled patterns of low titers demonstrated a probability index below 8. Regarding the pattern recognition, some types and mixed patterns are not properly recognized. Concerning the probability index correlated in some studies to final titer, the weak fluorescence of certain patterns and the random presence of artifacts that distort the index don't lead us to continue it in our daily practice. In conclusion, automated reading systems facilitate the reporting of results and traceability of patterns but still require the expertise of a laboratory technologist for positive/negative discrimination and for pattern recognition.

Automated Indirect Immunofluorescence Evaluation of Antinuclear Autoantibodies on HEp-2 Cells

PubMed Central

Voigt, Jörn; Krause, Christopher; Rohwäder, Edda; Saschenbrecker, Sandra; Hahn, Melanie; Danckwardt, Maick; Feirer, Christian; Ens, Konstantin; Fechner, Kai; Barth, Erhardt; Martinetz, Thomas; Stöcker, Winfried

2012-01-01

Indirect immunofluorescence (IIF) on human epithelial (HEp-2) cells is considered as the gold standard screening method for the detection of antinuclear autoantibodies (ANA). However, in terms of automation and standardization, it has not been able to keep pace with most other analytical techniques used in diagnostic laboratories. Although there are already some automation solutions for IIF incubation in the market, the automation of result evaluation is still in its infancy. Therefore, the EUROPattern Suite has been developed as a comprehensive automated processing and interpretation system for standardized and efficient ANA detection by HEp-2 cell-based IIF. In this study, the automated pattern recognition was compared to conventional visual interpretation in a total of 351 sera. In the discrimination of positive from negative samples, concordant results between visual and automated evaluation were obtained for 349 sera (99.4%, kappa = 0.984). The system missed out none of the 272 antibody-positive samples and identified 77 out of 79 visually negative samples (analytical sensitivity/specificity: 100%/97.5%). Moreover, 94.0% of all main antibody patterns were recognized correctly by the software. Owing to its performance characteristics, EUROPattern enables fast, objective, and economic IIF ANA analysis and has the potential to reduce intra- and interlaboratory variability. PMID:23251220

Is there a relationship between obesity and intracranial hypertension?

PubMed

Hannerz, J; Greitz, D; Ericson, K

1995-04-01

Intracranial hypertension and obesity have been reported in recent studies of patients with periorbital venous vasculitis. These findings indicate that obese patients should be investigated for signs of inflammation in serum and lumbar cerebrospinal fluid (CSF) pressure. Twenty obese females, aged 27-68 years participated in the study of associated symptoms, signs of inflammation in serum, intracranial hypertension and magnetic resonance imaging of the brain (MR). Twenty randomly selected age- and sex-matched females were also investigated for associated symptoms and MR as controls. There were no statistically significant differences in associated symptoms and diseases except for infertility (P < 0.05) between the two groups. The values for orosomucoid, haptoglobin, IgG, IgM and tests for rheumatic and antinuclear factors were significantly increased in the obese group compared with normal values at the hospital. The lumbar CSF pressure was increased above 20 cm water in 79% and above 25 cm water in 42% in the obese patients. MR showed that the subarachnoidal space in the obese patients were significantly smaller than in the controls. Signs of inflammation in serum, intracranial hypertension and decreased subarachnoidal space were statistically significantly more common in patients with obesity, than in controls.

Nuclear arms threat: psychosocial correlates of attitudes and behavioral response

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chilstrom, G.A.

1985-01-01

Why do some Americans believe a mutual (US-USSR) freeze on nuclear weapons production is the best way to prevent nuclear war, while others believe the strengthening of America's nuclear arsenal is the best answer. This study examined four psychological variables - dogmatism, intolerance of ambiguity, rigidity, and conformity - that might differentiate individuals with these opposing views. Also examined was the question of why some citizens are more actively engaged in peace activity than others. Subjects for the first part of the study were 146 student volunteers, predominantly undergraduate, from San Diego State University. Thirty-eight students were in favor ofmore » additional nuclear arms, while 108 advocated the freeze. The 108 subjects in the freeze group were also used in the second part of the study involving peace activity. In addition, a sample of 47 volunteers from various peace organizations in San Diego County were used to form a peace group. As predicted, individuals favoring a nuclear arms build-up were found to be significantly more rigid and conforming than individuals favoring a mutual freeze. However, no differences in dogmatism or intolerance of ambiguity were found between the two groups. With regard to peace activity, the results indicated that measures of locus of control were not significantly related to anti-nuclear activity, even when political ideology was taken into account. The highly activist peace group was found, however, to be significantly less conforming than the relatively non-activist freeze group.« less

[Establishment of systemic lupus erythematosus-like murine model with Sm mimotope].

PubMed

Xie, Hong-Fu; Feng, Hao; Zeng, Hai-Yan; Li, Ji; Shi, Wei; Yi, Mei; Wu, Bin

2007-04-01

To establish systemic lupus erythematosus (SLE) -like murine model by immunizing BALB/C mice with Sm mimotope. Sm mimotope was identified by screening a 12-mer random peptide library with monoclonal anti-Smith antibody. Sm mimotope was initially defined with sandwich ELISA, DNA sequencing, and deduced amino acid sequence; and BALB/C mice were subcutaneously injected with mixture phages clones. Sera Sm antibody, anti-double stranded DNA (dsDNA) antibody, and antinuclear antibody (ANA) of mice were detected using direct immunofluorescence; kidney histological changes were examined by HE staining. Five randomly selected peptides were sequenced and the amino acid sequences IR, SQ, and PP were detected in a higher frequency. High-titer IgG autoantibodies of dsDNA, Sm, and ANA in the sera of experiment group were detected by ELISA 28 days after having been immunized by Sm mimotope. Proteinuria was detected 33 days later; immune complex and nephritis were observed in kidney specimens. SLE-like murine model can be successfully induced by Sm phage mimotope.

Psychotherapist countertransference in the nuclear age: Effects on therapeutic interventions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oderberg, N.A.

Since the early 1980s, there has been considerable attention in the psychology literature to mental health problems related to living in a world threatened by nuclear destruction. Questionnaires were mailed to 630 psychotherapists from the Colorado Psychological Association, California Psychotherapists for Social Responsibility, California Psychologists for Social Responsibility, the US Army, and the APA Division of Military Psychology; 174 questionnaires were returned. It was hypothesized that liberalism, nuclear weapons opposition, nuclear concern, nuclear awareness, and anti-nuclear activism in psychotherapists would facilitate perception of, and openness to working with, a client's nuclear concerns and thus, would be positively correlated with intentionsmore » to discuss nuclear issues with clients in three different clinical vignettes. Results indicated that when controlling for subject group, psychotherapy orientation, age, sex, and income, all five independent variables were positively correlated with responses to all three clinical vignettes, with nuclear concern having the strongest unique effect in accounting for variance in responses to the vignettes.« less

Two Distinct Pathways in Mice Generate Antinuclear Antigen-Reactive B Cell Repertoires

PubMed Central

Faderl, Martin; Klein, Fabian; Wirz, Oliver F.; Heiler, Stefan; Albertí-Servera, Llucia; Engdahl, Corinne; Andersson, Jan; Rolink, Antonius

2018-01-01

The escape of anti-self B cells from tolerance mechanisms like clonal deletion, receptor editing, and anergy results in the production of autoantibodies, which is a hallmark of many autoimmune disorders. In this study, we demonstrate that both germline sequences and somatic mutations contribute to autospecificity of B cell clones. For this issue, we investigated the development of antinuclear autoantibodies (ANAs) and their repertoire in two different mouse models. First, in aging mice that were shown to gain several autoimmune features over time including ANAs. Second, in mice undergoing a chronic graft-versus-host disease (GVHD), thereby developing systemic lupus erythematosus-like symptoms. Detailed repertoire analysis revealed that somatic hypermutations (SHM) were present in all Vh and practically all Vl regions of ANAs generated in these two models. The ANA B cell repertoire in aging mice was restricted, dominated by clonally related Vh1-26/Vk4-74 antibodies. In the collection of GVHD-derived ANAs, the repertoire was less restricted, but the usage of the Vh1-26/Vk4-74 combination was still apparent. Germline conversion showed that the SHM in the 4-74 light chain are deterministic for autoreactivity. Detailed analysis revealed that antinuclear reactivity of these antibodies could be induced by a single amino acid substitution in the CDR1 of the Vk4-74. In both aging B6 and young GVHD mice, conversion of the somatic mutations in the Vh and Vl regions of non Vh1-26/Vk4-74 using antibodies showed that B cells with a germline-encoded V gene could also contribute to the ANA-reactive B cell repertoire. These findings indicate that two distinct pathways generate ANA-producing B cells in both model systems. In one pathway, they are generated by Vh1-26/Vk4-74 expressing B cells in the course of immune responses to an antigen that is neither a nuclear antigen nor any other self-antigen. In the other pathway, ANA-producing B cells are derived from progenitors in the bone marrow that express B cell receptors (BCRs), which bind to nuclear antigens and that escape tolerance induction, possibly as a result of crosslinking of their BCRs by multivalent determinants of nuclear antigens. PMID:29403498

Metabolic consequences of fluid shifts induced by microgravity

NASA Technical Reports Server (NTRS)

Cintron, N. M.; Lane, H. W.; Leach, C. S.

1990-01-01

The effects of fluid redistribution induced by weightlessness on the fluid and electrolyte regulation, the maintenance of optimum nutritional status, and on pharmacodynamics (i.e., the absorption, distribution, and elimination of pharmacologic agents) are examined on the basis of published data on flights aboard Skylab and Space Shuttle. Data are presented on changes in plasma osmolarity and the content of antinuclear factor, serum glucose, and the salivary scopolamine concentrations after oral administration before and during space flights.

25. AERIAL VIEW OF THE ROCKY FLATS PLANT LOOKING WEST ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

25. AERIAL VIEW OF THE ROCKY FLATS PLANT LOOKING WEST - NORTHWEST IN 1974. IN 1972, 4,600 ACRES WERE PURCHASED AROUND THE SITE TO BETTER PROTECT THE BORDERS FROM TERRORISM AND INFILTRATION BY PROTESTORS. ANTI-NUCLEAR DEMONSTRATION BEGAN SHORTLY AFTER THE 1969 FIRE IN BUILDING 776/777, AND CONTINUED UNTIL PRODUCTION CEASED AT THE PLANT IN 1989 (10/7/74). - Rocky Flats Plant, Bounded by Indiana Street & Routes 93, 128 & 72, Golden, Jefferson County, CO

Evaluation of serum anti-nuclear antibody among women with PCOS: a hospital based single center cross sectional study.

PubMed

Rashid, Aafia; Bhat, Javaid Ahmad; Ganie, Mohd Ashraf; Wani, Imtiyaz Ahmad; Bhat, Moomin Hussain; Shah, Zaffar Amin; Masoodi, Shariq R; Marwaha, R K

2018-05-07

Polycystic ovary syndrome (PCOS), a major endocrinopathy is associated with barrage of metabolic aberrations. Reports in literature on association of PCOS and autoimmunity are conflicting. We aim to evaluate serum levels of anti-nuclear antibody (ANA) among Indian women with PCOS. In this hospital-based single center cross-sectional study, women qualifying a diagnosis of PCOS by Rotterdam criteria 2003 were recruited. Eighty-nine eligible women who consented were enrolled. All these women along with 87 age-matched, healthy controls underwent, clinical (menstrual history, anthropometry, hirsutism scoring), biochemical, hormonal assessment and serum ANA estimation. OGTT after overnight (8-12 h) fast with 75 g oral glucose load was done for 1 h, 2 h glucose and insulin measurements. The mean age of cases and controls was comparable (22.67 ± 5.53 vs. 22.84 ± 3.64 years). The prevalence of ANA positivity was significantly higher among women with PCOS (18.4% vs. 2.29%; p < .001). Though significant correlation was observed between ANA positivity and clinical signs of hyperandrogenism and plasma glucose, no significant correlation was noted between ANA status and other hormonal parameters. Higher prevalence of ANA positivity among women with PCOS, being a marker of autoimmunity, suggests a possible role of autoimmunity in causation of PCOS and needs further elucidation.

Should we systematically test patients with clinically isolated syndrome for auto-antibodies?

PubMed

Negrotto, Laura; Tur, Carmen; Tintoré, Mar; Arrambide, Georgina; Sastre-Garriga, Jaume; Río, Jordi; Comabella, Manuel; Nos, Carlos; Galán, Ingrid; Vidal-Jordana, Angela; Simon, Eva; Castilló, Joaquín; Palavra, Filipe; Mitjana, Raquel; Auger, Cristina; Rovira, Àlex; Montalban, Xavier

2015-12-01

Several autoimmune diseases (ADs) can mimic multiple sclerosis (MS). For this reason, testing for auto-antibodies (auto-Abs) is often included in the diagnostic work-up of patients with a clinically isolated syndrome (CIS). The purpose was to study how useful it was to systematically determine antinuclear-antibodies, anti-SSA and anti-SSB in a non-selected cohort of CIS patients, regarding the identification of other ADs that could represent an alternative diagnosis. From a prospective CIS cohort, we selected 772 patients in which auto-Ab levels were tested within the first year from CIS. Baseline characteristics of auto-Ab positive and negative patients were compared. A retrospective revision of clinical records was then performed in the auto-Ab positive patients to identify those who developed ADs during follow-up. One or more auto-Ab were present in 29.4% of patients. Only 1.8% of patients developed other ADs during a mean follow-up of 6.6 years. In none of these cases the concurrent AD was considered the cause of the CIS. In all cases the diagnosis of the AD resulted from the development of signs and/or symptoms suggestive of each disease. Antinuclear-antibodies, anti-SSA and anti-SSB should not be routinely determined in CIS patients but only in those presenting symptoms suggestive of other ADs. © The Author(s), 2015.

Membranous glomerulopathy with spherules: an uncommon variant with obscure pathogenesis.

PubMed

Kowalewska, Jolanta; Smith, Kelly D; Hudkins, Kelly L; Chang, Anthony; Fogo, Agnes B; Houghton, Donald; Leslie, Deena; Aitchison, John; Nicosia, Roberto F; Alpers, Charles E

2006-06-01

Occasional case reports of membranous glomerulopathy described unique subepithelial accumulations of an unusual type of immune deposit composed of spherular structures. The identity of such structures as nuclear pores has been suggested, but not established. We identified a cohort of patients (n = 14, including 1 patient with disease recurrence in an allograft) who presented with nephrotic syndrome and had renal biopsy specimens with light and immunofluorescence microscopic findings characteristic of membranous glomerulopathy. These patients were distinguished by ultrastructural studies that showed glomerular capillary wall accumulations of subepithelial immune deposits composed of uniform spherular structures, while lacking the typical granular electron-dense deposits seen in membranous glomerulopathy. The molecular identity of these spherular structures as nuclear pores was tested by using immunofluorescence microscopy and immunohistochemistry with mouse monoclonal antinuclear pore antibodies (Covance, Princeton, NJ) and anti-Nuclear Pore-O-Linked Glycoprotein (Affinity BioReagents Inc, Golden, CO) antibodies. Measurement of spherular structures by using high-magnification electron microscopy showed an average diameter of 84.5 nm, which correlated well with accepted diameters of nuclear pores (80 to 120 nm). Immunofluorescence microscopy and immunoperoxidase staining with both antibodies showed characteristic beaded staining of nuclear membranes of multiple cell types within normal control kidney, but no staining of immune-type deposits within glomerular basement membranes. These cases form a rare, but distinctive, morphological subclass of membranous glomerulopathy. The antigenic specificity of immune deposits in these cases remains elusive.

Automated Processing and Evaluation of Anti-Nuclear Antibody Indirect Immunofluorescence Testing.

PubMed

Ricchiuti, Vincent; Adams, Joseph; Hardy, Donna J; Katayev, Alexander; Fleming, James K

2018-01-01

Indirect immunofluorescence (IIF) is considered by the American College of Rheumatology (ACR) and the international consensus on ANA patterns (ICAP) the gold standard for the screening of anti-nuclear antibodies (ANA). As conventional IIF is labor intensive, time-consuming, subjective, and poorly standardized, there have been ongoing efforts to improve the standardization of reagents and to develop automated platforms for assay incubation, microscopy, and evaluation. In this study, the workflow and performance characteristics of a fully automated ANA IIF system (Sprinter XL, EUROPattern Suite, IFA 40: HEp-20-10 cells) were compared to a manual approach using visual microscopy with a filter device for single-well titration and to technologist reading. The Sprinter/EUROPattern system enabled the processing of large daily workload cohorts in less than 8 h and the reduction of labor hands-on time by more than 4 h. Regarding the discrimination of positive from negative samples, the overall agreement of the EUROPattern software with technologist reading was higher (95.6%) than when compared to the current method (89.4%). Moreover, the software was consistent with technologist reading in 80.6-97.5% of patterns and 71.0-93.8% of titers. In conclusion, the Sprinter/EUROPattern system provides substantial labor savings and good concordance with technologist ANA IIF microscopy, thus increasing standardization, laboratory efficiency, and removing subjectivity.

Automated Processing and Evaluation of Anti-Nuclear Antibody Indirect Immunofluorescence Testing

PubMed Central

Ricchiuti, Vincent; Adams, Joseph; Hardy, Donna J.; Katayev, Alexander; Fleming, James K.

2018-01-01

Indirect immunofluorescence (IIF) is considered by the American College of Rheumatology (ACR) and the international consensus on ANA patterns (ICAP) the gold standard for the screening of anti-nuclear antibodies (ANA). As conventional IIF is labor intensive, time-consuming, subjective, and poorly standardized, there have been ongoing efforts to improve the standardization of reagents and to develop automated platforms for assay incubation, microscopy, and evaluation. In this study, the workflow and performance characteristics of a fully automated ANA IIF system (Sprinter XL, EUROPattern Suite, IFA 40: HEp-20-10 cells) were compared to a manual approach using visual microscopy with a filter device for single-well titration and to technologist reading. The Sprinter/EUROPattern system enabled the processing of large daily workload cohorts in less than 8 h and the reduction of labor hands-on time by more than 4 h. Regarding the discrimination of positive from negative samples, the overall agreement of the EUROPattern software with technologist reading was higher (95.6%) than when compared to the current method (89.4%). Moreover, the software was consistent with technologist reading in 80.6–97.5% of patterns and 71.0–93.8% of titers. In conclusion, the Sprinter/EUROPattern system provides substantial labor savings and good concordance with technologist ANA IIF microscopy, thus increasing standardization, laboratory efficiency, and removing subjectivity. PMID:29780386

Polyvalent immunoglobulins with vitamin D3 and vitamin B12 in the treatment of Sjogren's syndrome in a vegetarian with stomatitis, glossodynia, xerostomia, and elevated antinuclear antibodies: Case report
.

PubMed

Cuny, Clemens; Vaerst, Barbara; Gabrielpillai, Jennis; Tahtali, Aykut; Balster, Sven; Lissner, Reinhard; Woodcock, Barry G

2018-01-01

Sjogren's syndrome, involving sicca symptoms with xerostomia, stomatitis, and considerable pain is a difficult-to-treat autoimmune disease where the treatment options are limited and, as in the case of methotrexate, have a low therapeutic index. This case report concerns a male patient, aged 75 years and vegetarian, with Sjogren's syndrome subsequently confirmed by salivary gland biopsy. Serum antinuclear antibodies (ANA) were elevated (1 : 320). Low serum vitamin B12 and iron levels could be improved after 20 days using vitamin B12 and iron oral supplements. Despite symptomatic treatment, xerostomia, glossitis, and glossodynia were still present, at times marked, after 12 months when the ANA titer was unchanged. Following treatment with an anti-inflammatory polyvalent immunoglobulin formulation (Lactobin^®N, 7 g daily), a bovine colostrum concentrate given orally in combination with oral vitamin D3 (2,000 IU daily), sicca symptoms and xerostomia progressively decreased and at day 750 were confined to occasional and minor glossitis of the upper lip. This case report demonstrates the satisfactory control of Sjogren's syndrome using oral polyvalent immunoglobulins with vitamin D3. In contrast to treatment options involving antimalarial drugs and methotrexate, there are no safety issues in patients tolerant to milk products.
.

Autoantibodies in chronic hepatitis C virus infection and their association with disease profile.

PubMed

Williams, M J; Lawson, A; Neal, K R; Ryder, S D; Irving, W L

2009-05-01

Autoantibodies are commonly detected in chronic hepatitis C (HCV) but their significance remains uncertain. We assessed the prevalence of anti-nuclear (ANA) and anti-smooth muscle (ASM) antibodies within a cohort of 963 treatment-naïve HCV patients. We also assessed for differences between autoantibody-positive and autoantibody-negative patients in demographics, markers of disease activity and response to anti-viral treatment. One hundred and seventy-two patients (17.9%) had at least one autoantibody, of which were 104 (10.8%) ASM, 54 (5.6%) ANA and 14 (1.5%) positive for both. Autoantibody-positive patients were older (43 vs 39 years, P = 0.001) caused by an age-related increase in ANA (but not ASM). There were no differences in gender, alcohol intake, ethnicity or viral genotype. The presence of autoantibodies, and specifically ASM, was associated with an increase in interface hepatitis score amongst men (1.1 vs 0.8, P = 0.005) but no difference in other necroinflammatory measures, liver function tests or immunoglobulins (Ig). There was no difference in initial fibrosis stage or rate of fibrosis progression. Autoantibodies did not affect response to anti-viral treatment. We conclude that autoantibodies are frequent in HCV infection. Anti-nuclear antibodies increase with age, whereas ASM antibodies are associated with interface hepatitis in men. Neither autoantibody carries increased risk of fibrosis progression or failure of therapy.

Recent advances in the diagnosis and treatment of primary biliary cholangitis

PubMed Central

Huang, Ying-Qiu

2016-01-01

Primary biliary cholangitis (PBC), formerly referred to as primary biliary cirrhosis, is an infrequent progressive intrahepatic cholestatic autoimmune illness that can evolve into hepatic fibrosis, hepatic cirrhosis, hepatic failure, and, in some cases, hepatocellular carcinoma. The disease itself is characterized by T-lymphocyte-mediated chronic non-suppurative destructive cholangitis and elevated serum levels of extremely specific anti-mitochondrial autoantibodies (AMAs). In this article, we will not only review epidemiology, risk factors, natural history, predictive scores, radiologic approaches (e.g., acoustic radiation force impulse imaging, vibration controlled transient elastography, and magnetic resonance elastography), clinical features, serological characteristics covering biochemical markers, immunoglobulins, infections markers, biomarkers, predictive fibrosis marker, specific antibodies (including AMAs such as AMA-M2), anti-nuclear autoantibodies [such as anti-multiple nuclear dot autoantibodies (anti-sp100, PML, NDP52, anti-sp140), anti-rim-like/membranous anti-nuclear autoantibodies (anti-gp210, anti-p62), anti-centromere autoantibodies, and some of the novel autoantibodies], histopathological characteristics of PBC, diagnostic advances, and anti-diastole of PBC. Furthermore, this review emphasizes the recent advances in research of PBC in terms of therapies, including ursodeoxycholic acid, budesonide, methotrexate, obeticholic acid, cyclosporine A, fibrates such as bezafibrate and fenofibrate, rituximab, mesenchymal stem cells transplant, and hepatic transplant. Currently, hepatic transplant remains the only optimal choice with acknowledged treatment efficiency for end-stage PBC patients. PMID:27957241

[Variations of peripheral blood autoantibody, immunoglobuliln, and complement levels in patients with non-lactational mastitis and their clinical significances].

PubMed

Xu, Rui; Guo, Qian-Qian; Yang, Le-Ping; Lai, Mi-Lin; Tong, Lin

2016-08-20

To detect the variations in peripheral blood levels of autoantibodies, immunoglobulilns and complements in patients with non-lactational mastitis and investigate whether non-lactational mastitis is an autoimmune disease with immune dysfunction. Seven-eight patients with non-lactational mastitis treated in our hospital between September 2013 and May 2015 and 88 healthy women (control) were examined for peripheral blood levels of antinuclear antibody (ANA), anti-histone antibody (AHA), immunoglobulins (IgA, IgM, and IgG) and complements (C3, C4, and total complements). s Of the 78 patients with non-lactational mastitis, 50 (64.10%) were positive of ANA showing mainly the granular and cytoplasmic granular fluorescence patterns, and the positivity rate was significantly higher than that in the control group (P<0.000). Twenty-eight (36.00%) of the patients were positive of AHA, a rate significantly higher than that in the control group (P<0.000). The levels of IgA, IgM, C4, and total complements levels were all significantly elevated in the patients compared with those in the control group (P<0.05). Patients with non-lactational mastitis have abnormal changes in peripheral blood levels of immunoglobulins and complements with high positivity rates for ANA and AHA, indicating that non-lactational mastitis is an autoimmune disease with immune dysfunction.

[Changes in the thrombophilic status in patients with pre-eclampsia].

PubMed

Baptista-González, H A; Rosenfeld-Mann, F; Saavedra-Trejo, M R; Castro-López, J L; Peñuela-Olaya, M A

1999-04-01

The object of this study was to evaluate the changes in fibrinolysis and clotting inhibitors in patients with preeclampsia and to describe the connection between preeclampsia and blood pressure values. Two groups of pregnant women were prospectively studied at delivery: group 1 women without preeclampsia and group 2 patients with preeclampsia. The variables that were registered are: diastolic blood pressure (DBP), systolic blood pressure (SBP), mean blood pressure (MBP), hemoglobin (Hb), platelet count (Plt), lupus like inhibitor, anticardiolipin antibodies (ACA), antinuclear antibodies (ANA), fibronectina, D dimer, protein S (PS), protein C (PC) and vo Willebrand factor (vWF). 62 pregnant women were included. The patients of group 2 presented high values of Hb (p 0.01), fibronectin (p 0.0001), D-dimer (p 0.01) and lower PC (p 0.04). We found an association between fibronectin and higher values of SBP, DBP, MBP and Hb (p 0.0007) versus lower values of VFW and PC (p 0.002). The low values of total PS were associated with high D-dimer and SBP results (p 0.04 and 0.002 respectively). All patients were ACA/ANA negative. In preclampsia there is a increased hemoconcentration and drop in clotting inhibitors (PC), without fibrinolytic compensatory response (lower D-dimer) and remarked vasopressive effect (hig fibronectin). This changes depend on the stratification of blood pressure. Th SBP and MBP values depend on the haemodynamic changes (Hb, fibronectin), while the increase in DBP expresses a non compensated thrombophilic state.

Lupus Band Test in Patients with Borderline Systemic Lupus Erythematosus with Discoid Lesions.

PubMed

Akarsu, Sevgi; Ozbagcivan, Ozlem; Ilknur, Turna; Semiz, Fatma; Lebe, Banu; Fetil, Emel

2017-04-01

Patients with lupus erythematosus (LE) that have discoid lesions who fulfill the four diagnostic criteria of systemic lupus erythematosus (SLE) with only mucocutaneous findings and antinuclear antibody (ANA) positivity were classified as borderline SLE in the literature. Objective of this study was to determine the place of borderline SLE with discoid lesions on the LE spectrum according to the lupus band test (LBT). Lesional and sun-protected non-lesional (SPNL) skin LBTs of 94 patients with LE that had discoid lesions were retrospectively evaluated. Firstly, patients were divided into two main groups: discoid LE (DLE; group A) and SLE (Group B); three subgroups were then classified as DLE (Group A), borderline SLE (Group B1) and SLE (Group B2) using another method. Each group had its own comparisons. Immunoreactant (IR) deposition was observed on the lesional skin in all patients and on the SPNL skin in 42 (44.7%). In patients with borderline SLE, the deposition of IgM was lower on the lesional LBTs, whereas isolated IgG was higher than SLE; thus, it shows similarity with DLE. Additionally, it was also closer to DLE because of the low deposition of C3, multiple IRs, and a double conjugate of IRs on the SPNL skin. However, it showed similarity with SLE in the high percentage of LBT positivity and more immunoglobulin M (IgM) and immunoglobulin G (IgG) deposition on the SPNL skin. The deposition of multiple conjugates on SPNL skin in patients with LE with discoid lesions may reflect systemic involvement. Despite the fact that LBT positivity on SPNL skin in borderline SLE was higher than DLE, less deposition of multiple conjugates compared to SLE indicates that the classification of borderline SLE with discoid lesions in the LE spectrum is questionable.

[Lupus enteritis as initial manifestation of systemic lupus erythematosus. Report of one case].

PubMed

Barrera O, Manuel; Barrera M, Rodrigo; de la Rivera V, Matías; Vela U, Javier; Mönckeberg F, Gustavo

2017-10-01

Although gastrointestinal symptoms are not rare in Systemic lupus erythematosus, enteritis is an atypical manifestation of the disease. We report a 54 year-old woman who presented acute symptoms of diarrhea, fever and abdominal pain, receiving empiric antibiotic therapy for bacterial enteritis with no response. Computed tomography showed diffuse small intestine inflammation and serositis. Antinuclear antibodies, anti-Ro and anti-La were positive on blood tests. A lupic enteropathy was diagnosed and steroid treatment was initiated, with subsequent clinical improvement.

Preclinical Validation of Anti-Nuclear Factor Kappa B Therapy Against Vestibular Schwannoma and Neurofibromatosis Type II

DTIC Science & Technology

2016-06-01

therapies that simply reduce tumor volume and retard growth can be life- saving. The most successful drug used today to treat NF2, bevacizumab, works...in only about 50% of patients in halting tumor growth or causing tumor shrinkage. Bevacizumab is known to inhibit vascular endothelial growth factor...of TNF (and hence of NFkB) may prevent both VS growth and the associated hearing loss. Using human volumetric VS measurements in a retrospective

Lichen planus: a distinct entity from lupus erythematosus.

PubMed

Potts, E D; Rowell, N R

1981-01-01

Thirty-five patients with classical lichen planus (LP) were extensively investigated with special reference to immunohistological changes and histocompatibility (HLA) typing. There was no evidence of lupus erythematosus (LE) in any patient, although one patient with LP and eczema had an elevated titre of antinuclear factor. There was no increased incidence of any HLA type--in particular HLA-B7 and HLA-B8--known to be associated with LE. The results suggest that LE and LP are separate disorders.

Autoimmune hepatitis in childhood: the role of genetic and immune factors.

PubMed

Ferri Liu, Priscila Menezes; de Miranda, Débora Marques; Fagundes, Eleonora Druve Tavares; Ferreira, Alexandre Rodrigues; Simões e Silva, Ana Cristina

2013-07-28

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population.

Autoimmune hepatitis in childhood: The role of genetic and immune factors

PubMed Central

Ferri Liu, Priscila Menezes; de Miranda, Débora Marques; Fagundes, Eleonora Druve Tavares; Ferreira, Alexandre Rodrigues; Simões e Silva, Ana Cristina

2013-01-01

Autoimmune hepatitis (AIH) is a rare chronic inflammatory disease of the liver, which affects a group of patients who lost their immunological tolerance to antigens of the liver. It is clinically characterized by hypergammaglobulinemia, elevated liver enzymes, presence of autoantibodies and histological changes. Although being rare in children, it represents a serious cause of chronic hepatic disease that can lead to cirrhosis and hepatic failure. Clinical findings, exclusion of more common liver disorders and the detection of antibodies antinuclear antibodies, smooth muscle antibodies and anti-LKM1 are usually enough for diagnosis on clinical practice. The pathogenic mechanisms that lead to AIH remain obscure, but some research findings suggest the participation of immunologic and genetic factors. It is not yet knew the triggering factor or factors that stimulate inflammatory response. Several mechanisms proposed partially explain the immunologic findings of AIH. The knowledge of immune factors evolved might result in better markers of prognosis and response to treatment. In this review, we aim to evaluate the findings of research about genetic and immune markers and their perspectives of application in clinical practice especially in pediatric population. PMID:23901220

Response to Comment by Rabilloud on 'prevented Mortality and Greenhouse Gas Emissions from Historical and Projected Nuclear Power'

NASA Technical Reports Server (NTRS)

Kharecha, Pushker A.; Hansen, James

2013-01-01

The critique by Rabilloud-whose only listed professional affiliation is an antinuclear activist group?is grossly biased and contains numerous misleading, hyperbolic, and erroneous claims about our paper2 and about nuclear energy in general. The nature of his comments bears a striking resemblance to the fallacious reasoning commonly employed by climate change deniers to try to undermine public concern about the climate crisis. Specifically, he resorts to cherry-picking of information and diversionary (red herring) arguments, demands unrealistic exactness, and cites untrustworthy sources. None of his claims undermine any of the key results of our paper, most notably our conclusion that nuclear energy has prevented, and can continue to prevent, a very high number of fatalities and very large greenhouse gas emissions due to fossil fuel burning. It follows that, as uncomfortable as it is for many well-intentioned environmentalists to admit, efforts to undermine nuclear energy also undermine mitigation of climate change and air pollution, with a heavy cost in human lives and potentially disastrous future climate change.

Antinuclear antibody determination in a routine laboratory.

PubMed Central

Feltkamp, T E

1996-01-01

Pitfalls in the method for demonstrating antinuclear antibodies (ANA) by the indirect immunofluorescence technique are described and the use of international standard preparations outlined. Determination of the optimal border dilution dividing positive from negative results is discussed. Each laboratory is a unique setting; it must define its own method, which should rarely be changed. One should not rely on copying methods from other laboratories or commercial firms, but the reproducibility of the nuclear substrate, the conjugate, and other variables should be controlled daily by the use of a control serum which has been related to the WHO standard preparation for ANA of the homogeneous type. Since many sera contain mixtures of different ANA, the results of routine tests are best expressed in titres or expressions of the intensity of fluorescence. The ANA test using the immunofluorescence technique should be used as a screening method for other tests allowing a more defined interpretation of the ANA. Each laboratory should individually determine the border between positive and negative results. Therefore about 200 sera from local healthy controls equally distributed over sex and age, and 100 sera from local patients with definite SLE should be tested. Since the local clinicians should become acquainted with this border it should rarely be changed. Finally each laboratory should participate regularly in national and international quality control rounds, where sera known to be difficult to interpret are tested. The judgment of the organisers of these rounds should stimulate improvements in the participating laboratories. PMID:8984936

A Cross-Sectional Study of the Association between Autoantibodies and Qualitative Ultrasound Index of Bone in an Elderly Sample without Clinical Autoimmune Disease

PubMed Central

McEvoy, Mark; Kelly, Brian; Agnew, Linda; Walker, Frederick R.; Boyle, Michael

2018-01-01

Bone loss is characteristic of the ageing process and a common complication of many autoimmune diseases. Research has highlighted a potential role of autoantibodies in pathologic bone loss. The confounding effects of immunomodulatory drugs make it difficult to establish the contribution of autoantibodies amongst autoimmune disease sufferers. We attempted to examine the relationship between autoantibodies and bone mass in a population of 2812 elderly participants without clinical autoimmune disease. Serum samples were assayed for a panel of autoantibodies (anti-nuclear, extractable nuclear antigen, anti-neutrophil cytoplasmic, thyroid peroxidase, tissue transglutaminase, anti-cardiolipin, rheumatoid factor, and cyclic citrullinated peptide). Bone mass was measured using quantitative ultrasound (QUS) of the calcaneus. The relationship between each autoantibody and bone mass was determined using linear regression models. Anti-nuclear autoantibodies were the most prevalent, positive in approximately 11%, and borderline in roughly 23% of our sample. They were also the only autoantibody observed to be significantly associated with QUS index in the univariate analysis (n = 1628; r = −0.20; 95% CI: −0.40–0.00; p = 0.046). However, statistical significance was lost after adjustment for various other potential confounders. None of the other autoantibodies was associated with QUS index in either univariate or multivariate analysis. We are limited by the cross-sectional nature of the study and the low prevalence of autoantibodies in our nonclinical sample. PMID:29854851

How should a district general hospital immunology service screen for anti-nuclear antibodies? An ‘in-the-field’ audit

PubMed Central

Hira-Kazal, R; Shea-Simonds, P; Peacock, J L; Maher, J

2015-01-01

Anti-nuclear antibody (ANA) testing assists in the diagnosis of several immune-mediated disorders. The gold standard method for detection of these antibodies is by indirect immunofluorescence testing on human epidermoid laryngeal carcinoma (HEp-2) cells. However, many laboratories test for these antibodies using solid-phase assays such as enzyme-linked immunosorbent assay (ELISA), which allows for higher throughput testing at reduced cost. In this study, we have audited the performance of a previously established ELISA assay to screen for ANA, making comparison with the gold standard HEp-2 immunofluorescence test. A prospective and unselected sample of 89 consecutive ANA test requests by consultant rheumatologists were evaluated in parallel over a period of 10 months using both tests. ELISA and HEp-2 screening assays yielded 40 (45%) and 72 (81%) positive test results, respectively, demonstrating lack of concordance between test methods. Using standard and clinical samples, it was demonstrated that the ELISA method did not detect several ANA with nucleolar, homogeneous and speckled immunofluorescence patterns. None of these ELISANEG HEp-2POS ANA were reactive with a panel of six extractable nuclear antigens or with double-stranded DNA. Nonetheless, 13 of these samples (15%) originated from patients with recognized ANA-associated disease (n = 7) or Raynaud's phenomenon (n = 6). We conclude that ELISA screening may fail to detect clinically relevant ANA that lack defined specificity for antigen. PMID:25412573

Autoantibodies other than Anti-desmogleins in Pemphigus Vulgaris Patients

PubMed Central

Saleh, Marwah Adly; Salem, Hedayat; El Azizy, Hoda

2017-01-01

Background: Pemphigus vulgaris (PV) is an immunoglobulin G-mediated autoimmune bullous skin disease. Nonorgan-specific antibodies were detected in Tunisian and Brazilian pemphigus patients with different prevalence. Materials and Methods: Fifty PV patients and fifty controls were screened for antinuclear antibodies (ANAs), anti-smooth muscle antibodies (ASMAs), anti-parietal antibodies (APAs), anti-mitochondrial antibodies, and Anti-nuclear cytoplasmic antibodies (ANCA) by indirect immunofluorescence. Results: Thirty-nine patients were female and 11 were male. Fifteen patients did not receive treatment before while 35 patients were on systemic steroid treatment ± azathioprine. Twenty (40%) of the PV patients and 1 (2%) control had positive ANA. ANA was significantly higher in PV patients than controls, P < 0.0001. ASMAs were detected in 20 (40%) PV patients and none of the controls. ASMA was significantly higher in PV patients than controls, P < 0.0001. No significant difference was detected between treated and untreated regarding ANA, P - 0.11. However, there was a significant difference between treated and untreated regarding ASMA, P - 0.03. Six patients (12%) and none of the controls had positive APA. There was a significant difference between the patients and the controls in APA. P - 0.027. Conclusion: Egyptian PV patients showed more prevalent ANA, ASMA, and APA than normal controls. Follow-up of those patients is essential to detect the early development of concomitant autoimmune disease. Environmental factors might account for the variability of the nonorgan-specific antibodies among different populations. PMID:28216725

Features of Hepatitis in Hepatitis-associated Aplastic Anemia: Clinical and Histopathologic Study.

PubMed

Patel, Kalyani R; Bertuch, Alison; Sasa, Ghadir S; Himes, Ryan W; Wu, Hao

2017-01-01

Hepatitis-associated aplastic anemia (HAA) is a rare variant of aplastic anemia in which patients present with severe pancytopenia after an episode of acute hepatitis. The marrow failure is often rapid, severe, and usually fatal if untreated. The preceding hepatitis is largely under-studied. Retrospective study of the clinical and histopathologic features of hepatitis in pediatric patients who subsequently developed aplastic anemia and comparison with consecutive cases of acute liver failure and random cases of autoimmune hepatitis during the same time frame. All 7 patients of HAA had significant elevations in aminotransferases and conjugated hyperbilirubinemia at initial presentation. Echoing liver function indices, cholestatic hepatitis with sinusoidal obstruction-type endothelial injury was seen histomorphologically. Autoimmune hepatitis serology such as anti-F-actin, anti-liver/kidney microsome, and hypergammaglobulinemia was negative in all patients. Five of 7 patients (71.4%) had, however, elevated antinuclear antibody, all with a speckled pattern. Hepatitis virus serology was negative in all patients. By immunohistochemical staining, the lobular CD8/CD4 lymphocyte ratio was markedly elevated in all of the initial samples with significant reduction in this ratio (P = 0.03) in 3 patients post treatment (ursodiol, antibiotics, and/or immunosuppressive therapy). Hepatitis preceding HAA is characterized by marked elevation of aminotransferases, conjugated hyperbilirubinemia, elevated antinuclear antibody with a speckled pattern, cholestatic hepatitis with sinusoidal obstruction morphology, and CD8 dominant lobular infiltrates. The present study suggests HAA may result from cytotoxic T-cell-mediated sinusoidal endothelial and hepatocytic injury.

Nuclear energy in postwar Japan and anti-nuclear movements in the 1950s.

PubMed

Yamazaki, Masakatsu

2009-01-01

The atomic bombings of Hiroshima and Nagasaki in August 1945 revealed the most destructive power to-date of man-made weapons. Their impact was so great that Japanese scientists thought that a bigger disaster could be prevented only if war was abolished. Thus they welcomed the international control of atomic energy. It was, however, only after the occupation that the Japanese general public began to learn about the horror of these atomic disasters due to the censorship imposed by the occupational forces. The hydrogen bomb test by the US in the Bikini atoll on March 1, 1954 renewed fears of nuclear weapons. The crew of a Japanese fishing vessel, the "Daigo Fukuryu Maru" (Lucky Dragon No. 5) suffered from exposure to radiation from the test. Even after the incident the US did not stop nuclear tests which continued to radioactively contaminate fish and rains in Japan. As a result, the petition movement for the ban of nuclear trials suddenly spread all over the country. By the summer of 1955 the number of the signatures grew to more than one third of Japan's population at the time. Under the strong influence of anti-nuclear Japanese public opinion the Science Council of Japan announced the so-called three principles of atomic energy: "openness," "democracy," and "independence" to ensure atomic energy was used for peaceful uses only. These principles were included in the Atomic Energy Basic Law established in December 1955. With this law, military uses of nuclear energy were strictly forbidden.

Ramipril and haloperidol as promising approaches in managing rheumatoid arthritis in rats.

PubMed

Fahmy Wahba, Mariam Gamal; Shehata Messiha, Basim Anwar; Abo-Saif, Ali Ahmed

2015-10-15

Rheumatoid arthritis (RA) is a challenging autoimmune disorder, whose treatments usually cause severe gastrointestinal, renal and other complications. We aimed to evaluate the beneficial anti-arthritic effects of an angiotensin converting enzyme (ACE) inhibitor, ramipril and a dopamine receptor blocker, haloperidol, on Complete Freund's Adjuvant-induced RA in adult female albino rats. Rats were allocated into a normal control group, an arthritis control group, two reference treatment groups receiving dexamethasone (1.5 mg/kg/day) and methotrexate (1 mg/kg/day), and two treatment groups receiving ramipril (0.9 mg/kg/day) and haloperidol (1 mg/kg/day). Serum rheumatoid factor, matrix metalloprotinease-3 (MMP-3) and cartilage oligomeric matrix protein as specific rheumatoid biomarkers, serum immunoglobulin G and antinuclear antibody as immunological biomarkers, serum tumor necrosis factor alpha (TNF-α) and interleukin-10 (IL-10) as immunomodulatory cytokines, serum myeloperoxidase and C-reactive protein as inflammatory biomarkers, as well as malondialdehyde and glutathione reduced (GSH) as oxidative stress biomarkers were assessed. A histopathological study on joints and spleens was performed to support the results of biochemical estimations. Ramipril administration significantly corrected all the measured biomarkers, being restored back to normal levels except for MMP-3, TNF-α and IL-10. Haloperidol administration restored all the measured biomarkers back to normal levels except for TNF-α, IL-10 and GSH. In conclusion, ACE inhibitors represented by ramipril and dopamine receptor blockers represented by haloperidol may represent new promising protective strategies against RA, at least owing to their immunomodulatory, anti-inflammatory and antioxidant potentials. Copyright © 2015 Elsevier B.V. All rights reserved.

The effects of superovulation with gonadotropins on autoantibody levels in patients undergoing assisted reproductive cycles.

PubMed

Ashrafi, Mahnaz; Amirchaghmaghi, Elham; Arabipoor, Arezoo; Vesali, Samira; Salman-Yazdi, Reza

2018-04-25

To evaluate the effect of controlled ovarian stimulation (COH) with gonadotropins on the serum levels of autoantibodies in the women who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles and to compare basal levels of these autoantibodies between groups according to history of COH. This prospective cohort study was performed from October 2014 to March 2016 in the Royan Institute. The volunteered infertile women with regard to the inclusion criteria, who underwent IVF/ICSI cycles, were recruited. The COH was performed according to standard long GnRH agonist protocol. The mean levels of the autoantibodies including anti-nuclear, anti-smooth muscle, anti-ovarian, anti-mitochondrial, anti β 2 -glycoprotein I, anti-parietal cell and anti-follicle-stimulating hormone antibodies were measured at three time points: on the 3-5 days of the menstrual cycle, 1 week after starting of COH and the ovum pick-up (OPU) day. Of all participants (n = 189), 73 women had history of COH (group B) and 116 women did not have such history (group A). The analysis indicated that the autoantibodies changes during COH were similar in both groups. COH has no significant impact on the level of autoantibodies during the stimulation cycle. Multiple logistic regression analysis showed that the serum levels of anti-smooth muscle antibody on OPU day was the positive predictive factors for live birth following ART cycles in the studied population. No significant effect of COH on the studied autoantibodies by the time of OPU was found but further studies are required to interpret these results.

Extrahepatic manifestations associated with hepatitis C virus infection. A prospective multicenter study of 321 patients. The GERMIVIC. Groupe d'Etude et de Recherche en Medecine Interne et Maladies Infectieuses sur le Virus de l'Hepatite C.

PubMed

Cacoub, P; Renou, C; Rosenthal, E; Cohen, P; Loury, I; Loustaud-Ratti, V; Yamamoto, A M; Camproux, A C; Hausfater, P; Musset, L; Veyssier, P; Raguin, G; Piette, J C

2000-01-01

From January 1996 to January 1997, 321 patients with an average age of 46 +/- 16 years and chronically infected with hepatitis C virus (HCV) were prospectively enrolled in a study designed to determine the prevalence of extrahepatic manifestations associated with HCV infection in a large cohort of HCV patients, to identify associations between clinical and biologic manifestations, and to compare the results obtained in human immunodeficiency virus (HIV)-positive versus HIV-negative subsets. In a cross-sectional study, clinical extrahepatic manifestations, viral coinfections with HIV and/or hepatitis B virus, connective tissue diseases, and a wide panel of autoantibodies were assessed. Thirty-eight percent (122/321) of patients presented at least 1 clinical extrahepatic manifestation including arthralgia (60/321, 19%), skin manifestations (55/321, 17%), xerostomia (40/321, 12%), xerophthalmia (32/321, 10%), and sensory neuropathy (28/321, 9%). Main biologic abnormalities were mixed cryoglobulins (110/196, 56%), thrombocytopenia (50/291, 17%), and the presence of the following autoantibodies: antinuclear (123/302, 41%), rheumatoid factor (107/280, 38%), anticardiolipin (79/298, 27%), antithyroglobulin (36/287, 13%) and antismooth muscle cell (27/288, 9%). At least 1 autoantibody was present in 210/302 (70%) of sera. By multivariate logistic regression analysis, 4 parameters were significantly associated with cryoglobulin positivity: systemic vasculitis (p = 0.01, odds ratio OR[ = 17.3), HIV positivity (p = 0.0006, OR = 10.2), rheumatoid factor positivity (p = 0.01, OR = 2.8), and sicca syndrome (p = 0.03, OR = 0.27). A definite connective tissue disease was noted in 44 patients (14%), mainly symptomatic mixed cryoglobulinemia and systemic vasculitis, HIV coinfection (23%) was associated with 3 parameters: anticardiolipin (p = 0.003, OR = 4.18), thrombocytopenia (p = 0.01, OR = 3.56), and arthralgia or myalgia (p = 0.017, OR = 0.23). HIV-positive patients presented more severe histologic lesions (p = 0.0004). Extrahepatic clinical manifestations in HCV patients involve primarily the skin and joints. The most frequent immunologic abnormalities include mixed cryoglobulins, rheumatoid factor, antinuclear, anticardiolipin, and antithyroglobulin antibodies. Cryoglobulin positivity is associated with systemic vasculitis and rheumatoid factor and HIV positivity. HIV coinfection is associated with arthralgia or myalgia, anticardiolipin antibodies, and thrombocytopenia.

High sensitive detection of double-stranded DNA autoantibodies by a modified Crithidia luciliae immunofluorescence test.

PubMed

Conrad, Karsten; Ittenson, Annelore; Reinhold, Dirk; Fischer, Richard; Roggenbuck, Dirk; Büttner, Thomas; Bosselmann, Hans-Peter; Steinbach, Jörg; Schössler, Werner

2009-09-01

Anti-double-stranded (ds)DNA antibodies are serological markers of systemic lupus erythematosus (SLE). Of all anti-dsDNA antibody detection methods, the Crithidia luciliae immunofluorescence test (CLIFT) is thought to have the highest specificity for SLE. However, the clinical application is hampered by the low diagnostic sensitivity. A CLIFT with modified assay buffer (mCLIFT) was developed and compared with conventional CLIFT, using sera from 110 patients with SLE, 89 anti-dsDNA ELISA-positive patients with other diseases (non-SLE group A), 157 non-SLE patients with undetectable anti-dsDNA antibodies by ELISA (non-SLE group B), 77 disease controls (non-SLE group C), and 50 healthy blood donors. Out of the 110 anti-dsDNA antibody ELISA-positive SLE patients, 84 (76.4%) demonstrated a positive kinetoplast staining, using the mCLIFT, compared to only 42.3%, using the conventional CLIFT. The diagnostic specificity of mCLIFT was 100% with healthy blood donors and 98.1% with the non-SLE group C (anti-nuclear antibodies negative; no signs or symptoms of an autoimmune disease) included. In the non-SLE groups A and B with various other autoimmune diseases or symptoms of a possible autoimmune disease, positive mCLIFT results were obtained in 33.7% and 3.2%, respectively. In conclusion, by modification of the assay buffer, a significant increase in sensitivity of the CLIFT could be observed while retaining the high specificity for SLE. Further investigation is required to check whether the CLIFT-positive non-SLE patients develop SLE and whether anti-dsDNA antibodies detected by the mCLIFT represent a pathogenetic and diagnostic subgroup of autoantibodies that may improve the early diagnosis of SLE or SLE-overlap syndromes.

Risk factors associated with a new pregnancy loss and perinatal outcomes in cases of recurrent miscarriage treated with lymphocyte immunotherapy.

PubMed

Cavalcante, Marcelo Borges; Costa, Fabrício da Silva; Araujo Júnior, Edward; Barini, Ricardo

2015-06-01

To assess the perinatal outcomes and risk factors for further pregnancy loss in patients with recurrent miscarriage treated with lymphocyte immunotherapy (LIT). We performed a retrospective observational study of women with a history of two or more consecutive miscarriages who underwent LIT. All patients had undergone investigation of the etiology of the pregnancy losses according to a specific protocol. These etiologic factors were compared between those whose pregnancy outcome was successful and those who had a further miscarriage. The comparison between the groups was performed by Kruskal-Wallis, Fisher exact and Chi-square tests. Perinatal outcome data were collected for the successful pregnancies. One-hundred six patients were included. The mean number (±SD) of previous pregnancies, deliveries and miscarriages in all patients were 2.73 ± 0.8, 0.19 ± 0.4 and 2.54 ± 0.6, respectively. A successful pregnancy outcome after lymphocyte therapy occurred in 82 patients (group I), while 24 (22.6%) sustained a further miscarriage (group II). There was no statistical difference in the genetic, anatomic and hormonal causes of miscarriage between the groups (p > 0.05). Antinuclear (ANA) and antithyroglobulin (TgAb) autoantibodies occurred more frequently in group II (p = 0.0010 and p = 0.0024, respectively). Of those with successful pregnancies, 11 women (13.4%) had a preterm delivery. The mean birth weight was 3036.4 ± 498.6 g. In patients with recurrent miscarriage treated with LIT, the presence of ANA and TgAb was a risk factor for further pregnancy loss. Perinatal outcomes in those whose pregnancies continued were favorable.

[Rheumatic features of Grave's disease in children].

PubMed

Chávez-Legaspi, M; Ocampo-Campos, R; García-Velarde, E; Ríos-González, J

1992-01-01

We report three cases from girls with Graves disease who developed serious rheumatic manifestations. One patient had systemic lupus erythematosus with articular, renal, neurological and cardiac afectation with fatal outcome. Other patient presented clinical features of scleroderma with skin thickness, myopathy, arthritis, Raynaud's phenomenon and findings of pulmonary fibrosis. A lupus-like syndrome associated to methimazole therapy (polyarthritis, rash and hemolytic anemia) with positive Cel-LE preparations but negative antinuclear-antibodies was observed in a third patient. A careful history and the recognition of these manifestations will help in the identification of these syndromes.

Reassessing the Security Treaty Between Australia, New Zealand, and the United States (ANZUS): Post-Cold War Security Relations

DTIC Science & Technology

1998-01-01

Zealand in the World Since 1945 ( Auckland , New Zealand: 1975), 25. 23 Keith Sinclair, 31. 24 T.B. Millar, 221. 25 T.B. Millar, 143. 26 T.B...outrage that spilled over into anti-nuclear opinion. Further fuel to the fire was that the bombing had taken place inside the port of Auckland ; New...superficially seems to do in pure monetary terms but the purported increase in spending “…would not raise the proportion of the nation’s GDP , but would

The prevalence of autoantibody and its relationship with genotypes of hepatitis C virus in patients with chronic hepatitis C virus infection.

PubMed

Kirdar, Sevİn; Sener, Asli Gamze; Cengİz, Merve; Aydin, Nerİman

2016-11-01

The prevalence of autoantibody in the patients with chronic hepatitis C infection, and the relationship between the autoantibodies and HCV genotypes were investigated in this study. One hundred and eight anti-HCV positive and 86 anti-HCV negative patients were included in the study. Anti-HCV were studied by enzyme immunassay (EIA). HCV RNA was determined by real time polymerase chain reaction (PCR) and HCV genotypes were determined by a reverse-line blot hybridization. Anti-nuclear antibodies (ANA), anti-smooth muscle antibodies (ASMA), Anti-mitochondrial antibodies (AMA), liver kidney microsomal antibodies (LKM) were detected by indirect immunofluorescence assay. Among patients, 13 (12.03%) of 108 were positive for at least one autoantibody. The positivity was not observed in control group. The most prevalent autoantibody in anti-HCV positive group was ANA. ANA was positive in six HCV patients with genotype 1. In HCV patients with genotype 1, the frequencies of ANA, ASMA, AMA and LKM1 were six, two, three and one, respectively. In HCV patients with genotype 2, ANA was positive one patient and ASMA, AMA and LKM1 were not detected in HCV patients with genotype 2. In conclusion, the autoantibodies in patients with chronic hepatitis C in the study were low as compared to those reported in previous studies. © 2016 APMIS. Published by John Wiley & Sons Ltd.

[Systemic lupus erythematosus in the native inhabitants of Tadzhikistan].

PubMed

Rasulov, U R

1990-01-01

A total of 106 patients with systemic lupus erythematosus (SLE) underwent clinico-laboratory comparative studies. There were 3 groups of patients. Of these, 43 patients were examined in Moscow, 34 natives of Tadzhikistan (Tadzhiks and Uzbeks), and 29 patients belonging to the nonindigenous population were examined in Dushanbe. For estimation purposes use was made of routine clinical-instrumental and laboratory methods including the determination of antinuclear factor (ANF). The clinicoimmunological features of SLE seen in the natives of Tadzhikistan consisted in a more frequent demonstration of facial erythema, arthritis, oral ulcerations and clinical criteria for ARA on the whole; in a rarer demonstration of capillaritis, serositis, and laboratory criteria for ARA including ANF. SLE patients belonging to the non-indigenous population of Tadzhikistan occupy an intermediate place between SLE patients belonging to the indigenous population and patients living in Moscow. By their clinico-laboratory parameters, however, they are closer to the Moscow group patients excluding the age at which the disease occurs. In the nonindigenous population of Tadzhikistan, the disease appeared to start 10 years later. The clinico-laboratory differences as well as those in the age of the disease onset in the indigenous and nonindigenous population of Tadzhikistan form the basis for elaborating the medical and social measures with a purpose of goal-oriented identification of factors at risk for the development of SLE in Tadzhikistan bearing in mind the ethnic characteristics.

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: A cross-sectional study

PubMed Central

Gardner, Renee M.; Nyland, Jennifer F.; Silva, Ines A.; Ventura, Ana Maria; Souza, Jose Maria de; Silbergeld, Ellen K.

2010-01-01

Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of autoantibodies directed at antigens located in the nucleus (anti-nuclear autoantibodies, or ANA) or the nucleolus (anti-nucleolar autoantibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well-controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socioeconomic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold-miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1β, TNF-α, and IFN-γ in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations. PMID:20176347

[Endothelial response for the presence of chosen antinuclear antibodies, anti-Ro (SS-A) and anti-La (SS-B) and anti-Sm in vasculitis against the background of existing lupus erythematosus].

PubMed

Doskocz, R; Adamiec, R; Kwiatkowska, W; Alexewicz, P; Doskocz, W; Adamiec, J

1999-11-01

Systemic lupus erythematodes is a disease commonly associated with peripheric circulation disturbances. The goal of the study was the evaluation of the role of the following nuclear antibodies: anti-Ro (SS-A), anti-La (SS-B) and anti-Sm in the endothelium damage process in the SLE patients with symptoms of microcirculation disturbances. The concentration of plasma thrombomodulin was used as a marker of the endothelium destructive changes intensity. Twenty-four patients with SLE (22 women and 2 man) aged of 18-57 (the average age 40.50 +/- 9.72 years) in which occurred: the Raynauds symptom (16 patients), fingers cyanosis (5 patients) and fingers and/or toes necrosis (3 patients) were investigated. Antinuclear antibodies and thrombomodulin level was estimated with the ELISA method. In all patients, the concentration of anticardiolipin antibodies in serum was determined (ELISA-method, cardiolipin was used as an antigenes, Sigma USA). Higher titers of ANA antibodies in 83%, anti-SM antibodies in 30%, anti-Ro in 42% and anti-La in 42%, examined patients and higher titer of anti-Ro and anti-La antibodies together in 29% of examined patients were stated. Statistical significant correlation between the increased level of thrombomodulin and anti-La antibodies concentrations in serum of patients with the disease lasting over 6 years was found out. The significant statistical correlation of thrombomodulin concentration increasing and anti-La antibodies in serum was proved. The dynamism of limbs circulation disorders depends on the disease duration.

Chronic Malaria Revealed by a New Fluorescence Pattern on the Antinuclear Autoantibodies Test

PubMed Central

Hommel, Benjamin; Charuel, Jean-Luc; Jaureguiberry, Stéphane; Arnaud, Laurent; Courtin, Regis; Kassab, Petra; Prendki, Virginie; Paris, Luc; Ghillani-Dalbin, Pascale; Thellier, Marc; Caumes, Eric; Amoura, Zahir; Mazier, Dominique; Musset, Lucile; Buffet, Pierre; Miyara, Makoto

2014-01-01

Background Several clinical forms of malaria such as chronic carriage, gestational malaria or hyper-reactive malarial splenomegaly may follow a cryptic evolution with afebrile chronic fatigue sometimes accompanied by anemia and/or splenomegaly. Conventional parasitological tests are often negative or not performed, and severe complications may occur. Extensive explorations of these conditions often include the search for antinuclear autoantibodies (ANA). Methods We analysed fluorescence patterns in the ANA test in patients with either chronic cryptic or acute symptomatic malaria, then conducted a one-year prospective study at a single hospital on all available sera drawn for ANA detections. We then identified autoantibodies differentially expressed in malaria patients and in controls using human protein microarray. Results We uncovered and defined a new, malaria-related, nucleo-cytoplasmic ANA pattern displaying the specific association of a nuclear speckled pattern with diffuse cytoplasmic perinuclearly-enhanced fluorescence. In the one-year prospective analysis, 79% of sera displaying this new nucleo-cytoplasmic fluorescence were from patients with malaria. This specific pattern, not seen in other parasitic diseases, allowed a timely reorientation of the diagnosis toward malaria. To assess if the autoantibody immune response was due to autoreactivity or molecular mimicry we isolated 42 autoantigens, targets of malarial autoantibodies. BLAST analysis indicated that 23 of recognized autoantigens were homologous to plasmodial proteins suggesting autoimmune responses directly driven by the plasmodial infection. Conclusion In patients with malaria in whom parasitological tests have not been performed recognition of this new, malaria-related fluorescence pattern on the ANA test is highly suggestive of the diagnosis and triggers immediate, easy confirmation and adapted therapy. PMID:24551116

Measurement of antinuclear antibodies and their fine specificities: time for a change in strategy?

PubMed

Otten, Henny G; Brummelhuis, Walter J; Fritsch-Stork, Ruth; Leavis, Helen L; Wisse, Bram W; van Laar, Jacob M; Derksen, Ronald H W M

2017-01-01

The current strategy for antinuclear antibody (ANA) analysis involves screening for presence with a subsequent detailed analysis of their specificity. The aim of this study is to compare the clinical and financial efficacy of this strategy between different commercial tests in a large cohort of unselected patients. In all consecutive 1030 patients associations were defined between results from different ANA test systems and the pre-test probability for connective tissue disease (CTDs). Test systems were used for screening (ANA-IIF vs. CTD screen) and definition of their fine specificity (profile 3 line blot vs. CTD single analytes). Positive ANA-IIF and/or CTD screen results were found in 304 sera. Further analysis for ANA-specificity by profile 3 line blot and CTD single analytes showed 86 discrepant results of which more than a third are clinically relevant, with the CTD single analyte assay performing better than the line blot in supporting or confirming the presence of a CTD. Autoantigens present in one test but absent in the other were of minor practical use. The ANA screening and identification strategies currently employed are not cost-effective as 83% of tests were performed in order to find specific autoantibodies in patients without the fitting clinical signs or symptoms. This causes many unexpected positive results and subsequent confusion with regard to interpretation. We advocate that some autoantigens should be excluded from the line blot and CTD assays and propose the use of a cost-effective and selective ANA specificity testing purely based on clinical guidance.

Chicken or the egg: anorexia nervosa and systemic lupus erythematosus in children and adolescents.

PubMed

Toulany, Alene; Katzman, Debra K; Kaufman, Miriam; Hiraki, Linda T; Silverman, Earl D

2014-02-01

Systemic lupus erythematosus (SLE) frequently has neuropsychiatric involvement including affective disorders, psychosis, and cognitive dysfunction. Evidence suggests that anorexia nervosa (AN) in adolescents with SLE may be triggered by steroid-induced changes in weight and body shape. We propose that AN may be another manifestation of neuropsychiatric SLE and should be considered in this patient population. A retrospective chart review identified 7 children/adolescents diagnosed with SLE and the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnostic criteria for AN, restrictive subtype, at the Hospital for Sick Children in Toronto between January 1989 and January 2011. One patient developed AN 15 months after being diagnosed with SLE that was attributed to prednisone-induced weight gain and cushingoid appearance. Of the remaining 6 patients, the median age at onset of AN symptoms was 12.2 years and diagnosis of AN was 13.6 years. The median age at SLE diagnosis was 14.2 years with median time after onset of AN symptoms of 20 months (7.5-32 months). All patients had evidence of joint symptoms and a positive antinuclear antibody, and 50% had lymphopenia at the time of SLE diagnosis. Treatment of SLE resulted in improvement of AN in all patients. The timing of the clinical presentation of AN in relation to the diagnosis of SLE and response to SLE treatment suggests that AN may be a novel presentation of neuropsychiatric SLE. Patients with AN who present with or develop joint symptoms, a positive antinuclear antibody, or lymphopenia should be investigated and followed for possible SLE.

Impact of borderline-subclinical hypothyroidism on subsequent pregnancy outcome in women with unexplained recurrent pregnancy loss.

PubMed

Uchida, Sayaka; Maruyama, Tetsuo; Kagami, Maki; Miki, Fumie; Hihara, Hanako; Katakura, Satomi; Yoshimasa, Yushi; Masuda, Hirotaka; Uchida, Hiroshi; Tanaka, Mamoru

2017-06-01

Because subclinical hypothyroidism (thyroid-stimulating hormone [TSH] > 4.5 IU/mL) is associated with adverse pregnancy outcome, including early pregnancy loss, TSH is recommended to be titrated to ≤2.5 mIU/L in levothyroxine-treated women before pregnancy. The purpose of this study was to determine whether borderline-subclinical hypothyroidism (borderline-SCH; 2.5 < TSH ≤ 4.5 IU/mL) affects the outcome of subsequent pregnancies in women with unexplained recurrent pregnancy loss (uRPL). After workup for antinuclear antibody (ANA), anti-phospholipid syndrome, thrombophilia, uterine abnormalities, hormone disorders, and/or chromosomal abnormalities, 317 women with a history of uRPL were enrolled. The women were classified into two groups: borderline-SCH, and euthyroidism (0.3 ≤ TSH ≤ 2.5 IU/mL). All women had normal serum free thyroxine (T4) and did not receive levothyroxine before or during the subsequent pregnancy. There were no significant differences in age, number of previous pregnancy losses, number of live births, or body mass index between the borderline-SCH (n = 56) and the euthyroid (n = 261) groups, but the rate of ANA positivity differed significantly (53.6% vs 33.7%, respectively; P = 0.005). The subsequent pregnancy rate did not differ between the two groups (55.4%, 31/56 vs 51.3%, 134/261, respectively). The pregnancy loss rate (<22 weeks of gestation) tended to be higher in the borderline-SCH than the euthyroid group (29.0%, 9/31 vs 17.9%, 24/134), although not significantly so (P = 0.16). Although some subset of uRPL is though to be due to as-yet-unidentified cause(s), borderline-SCH is unlikely to be involved in uRPL. © 2017 Japan Society of Obstetrics and Gynecology.

Prevalence of positive autoimmune biomarkers in the brucellosis patients.

PubMed

Ahmadinejad, Zahra; Abdollahi, Alireza; Ziaee, Vahid; Domiraei, Zeinab; Najafizadeh, Seyed-Reza; Jafari, Sirus; Ahmadinejad, Mahdi

2016-10-01

Brucellosis is a chronic infectious disease with articular involvement. Discrimination between brucellosis and rheumatologic disorders is difficult in regions endemic for brucellosis. There are few studies about the rate of positive autoantibodies as rheumatologic biomarkers in brucellosis, and the prevalence is variable. In this study, the rheumatologic tests were studied in brucellosis patients. This cross sectional study was performed in two teaching hospitals in Tehran, Iran. Forty-nine patients with brucella infection and 42 healthy participants were enrolled in this study. Brucellosis was diagnosed on the basis of the clinical symptoms and positive serology for brucellosis. Rheumatic factor (RF) and antinuclear antibodies (ANA) were evaluated in all patients. Cyclic citrullinated peptides antibody (ACPA) and anti-double strand DNA (anti-dsDNA) were checked in all patients and control groups. Out of 49 patients, 15 (30.6 %) were RF positive and 4 (8.2 %) were ANA positive. Anti-dsDNA was concurrently positive with ANA in 1 patient (2 %) but ACPA titer was positive in 8 patients (16.3 %). None of the patients with positive autoantibody biomarkers fulfilled the criteria for rheumatologic disorders. The rate of positive RF in healthy people was significantly lower than patient group (2.4 vs. 30.6 %), but the positiveness rate of other biomarkers did not have significant difference in two groups. Sixty percent of the patients with positive RF and 75 % with positive ACPA had skeletal involvement (P < 0.05). Autoantibody biomarkers can be positive in brucellosis. Rheumatologists should be aware of brucellosis in patients with musculoskeletal involvement and positive autoantibody biomarkers in endemic regions.

Thrombotic thrombocytopenic purpura misdiagnosed as autoimmune cytopenia: Causes of diagnostic errors and consequence on outcome. Experience of the French thrombotic microangiopathies reference centre.

PubMed

Grall, Maximilien; Azoulay, Elie; Galicier, Lionel; Provôt, François; Wynckel, Alain; Poullin, Pascale; Grange, Steven; Halimi, Jean-Michel; Lautrette, Alexandre; Delmas, Yahsou; Presne, Claire; Hamidou, Mohamed; Girault, Stéphane; Pène, Frédéric; Perez, Pierre; Kanouni, Tarik; Seguin, Amélie; Mousson, Christiane; Chauveau, Dominique; Ojeda-Uribe, Mario; Barbay, Virginie; Veyradier, Agnès; Coppo, Paul; Benhamou, Ygal

2017-04-01

Thrombotic thrombocytopenic purpura (TTP) has a devastating prognosis without adapted management. Sources of misdiagnosis need to be identified to avoid delayed treatment. We studied 84 patients with a final diagnosis of severe (<10%) acquired ADAMTS13 deficiency-associated TTP from our National database that included 423 patients, who had an initial misdiagnosis (20% of all TTP). Main diagnostic errors were attributed to autoimmune thrombocytopenia, associated (51%) or not (37%) with autoimmune hemolytic anemia. At admission, misdiagnosed patients were more frequently females (P = .034) with a history of autoimmune disorder (P = .017) and had organ involvement in 67% of cases; they had more frequently antinuclear antibodies (P = .035), a low/undetectable schistocyte count (P = .001), a less profound anemia (P = .008), and a positive direct antiglobulin test (DAT) (P = .008). In multivariate analysis, female gender (P = .022), hemoglobin level (P = .028), a positive DAT (P = .004), and a low schistocytes count on diagnosis (P < .001) were retained as risk factors of misdiagnosis. Platelet count recovery was significantly longer in the misdiagnosed group (P = .041) without consequence on mortality, exacerbation and relapse. However, patients in the misdiagnosed group had a less severe disease than those in the accurately diagnosed group, as evidenced by less organ involvement at TTP diagnosis (P = .006). TTP is frequently misdiagnosed with autoimmune cytopenias. A low schistocyte count and a positive DAT should not systematically rule out TTP, especially when associated with organ failure. © 2017 Wiley Periodicals, Inc.

[Side effects of the HMG-CoA reductase inhibitors (statins). Lupus erythematosus induced by Atorvastatin therapy].

PubMed

Hydzik, Piotr; Szpak, Dorota

2011-01-01

The paper describes the case of 56 years old woman admitted to the Toxicology Department because of skin lesions, joint and muscle pain and elevated activity of transaminases and creatine phosfokinase as well in biochemical analysis. The symptoms occurred after 6 days of the Atorvastatin therapy. The clinical picture indicated side effects of the hipolipemic therapy, but the presence of the skin lesions suggested drug induced collagenosis (lupus erythrematosus, dermatomyositis). Immunological studies confirmed association with antinuclear antibodies (ANA) and anti-Mi-2 autoantibodies in the serum. Immunosuppressive therapy was ordered with clinical and biochemical improvement.

Complete atrioventricular block as initial manifestation of systemic lupus erythematosus.

PubMed

Arce-Salinas, C A; Carmona-Escamilla, M A; Rodríguez-García, F

2009-01-01

Only a few cases of complete atrioventricular block (AVB) in adult lupus patients have been previously described, but only one as the initial manifestation. A 19-year-old woman who presented with seizures and loss of consciousness, was diagnosed with complete ABV and underwent pacemaker placement. Over the next weeks she developed serositis, joint, cutaneous, and renal involvement; positive antinuclear antibodies and high anti-SSA/Ro titers. This is the second case with AVB as a feature of SLE at onset. A review of previous complete AVB cases of adult SLE patients is presented.

Transaction Design Specification Medical Exam Databases System (MED) update Transaction

DTIC Science & Technology

1986-12-01

8217RECOFD IN 51) 73. CORONARY SFAS1 SITE ;CHAR X(6) IN 7:) 74* CORONARY FLAQUES (RECO D IN 51) 75. CCFONARY PLAOUE 3ITE ,CHAR K(60 IN 74) 76* FCT DIAMETER...KETOSTEROIDS YE HYDROXYCARTICOSTEROIDS YO 24 HR URINE TOTAL VOLUME MA URINE OSMOLALITY MB SERUM OSMOLALITY MC 24HR URINE TOTAL VOLUME ZE SERUM COPPER FBS TO...RHEUMATOID FACTOR PA N P -2 2 ANTINUCLEAR ANTIBODY PB N P -2 2 0 FREE FATTY ACIDS QA 5 9 57 200 MG% SERUM COPPER RA 30 70 130 300 JG% URINE COPPER RBM 10 30 90

Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India

PubMed Central

2012-01-01

Background Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population. Methods Effect of chronic arsenic exposure on liver was determined by liver function tests. Autoimmune status was measured by measuring ANA and anti-dsDNA in serum. Inflammatory cytokines associated with increased cardiovascular disease risk, IL6, IL8 and MCP-1 were determined. Results Our results indicated that serum levels of bilirubin, alanine transaminase, aspartate transaminase, alkaline phosphatase and ANA were increased in the arsenic exposed population. Serum levels of IL6 and IL8 also increased in the arsenic exposed group. Conclusions Chronic arsenic exposure causes liver injury, increases the serum levels of autoimmune markers and imparts increased cardiovascular risk. PMID:22883023

The commercial use of gamma facilities in North and South America for agriculture product processing

NASA Astrophysics Data System (ADS)

Butterweck, Joseph S.

1993-07-01

The treatment of agriculture and food products with ionizing radiation has been proven to be safe, effective, economical, and according to consumer surveys, the end product is better. However, commercial implementation of food irradiation has been slow because the following: 1. The lack of profit incentives 2. The failure of the political system to deal with antinuclear groups 3. The failure of public health authorities to actively support this technologyFood irradiation cannot be considered successfully implemented until the commercial industry is making a profit by the use of this technology. Use of this technology will: (1) reduce food borne infections (FBI); (2) decrease the hazards of the use of antibiotics in livestock and poultry production; (3) reduce the need for agriculture quarantine procedures; and (4) increase shelf-life of perishable foods. However, only (1) and (3) are being considered as economic alternative by the present day's food industry. Previously, agriculture has focused on technology that would increase production and reduce costs. Today this is rapidly changing to implementing technology that markets a product the consumer wants and is perceived as being safer and environmental responsible.

CVID-associated TACI mutations affect autoreactive B cell selection and activation

PubMed Central

Romberg, Neil; Chamberlain, Nicolas; Saadoun, David; Gentile, Maurizio; Kinnunen, Tuure; Ng, Yen Shing; Virdee, Manmeet; Menard, Laurence; Cantaert, Tineke; Morbach, Henner; Rachid, Rima; Martinez-Pomar, Natalia; Matamoros, Nuria; Geha, Raif; Grimbacher, Bodo; Cerutti, Andrea; Cunningham-Rundles, Charlotte; Meffre, Eric

2013-01-01

Common variable immune deficiency (CVID) is an assorted group of primary diseases that clinically manifest with antibody deficiency, infection susceptibility, and autoimmunity. Heterozygous mutations in the gene encoding the tumor necrosis factor receptor superfamily member TACI are associated with CVID and autoimmune manifestations, whereas two mutated alleles prevent autoimmunity. To assess how the number of TACI mutations affects B cell activation and tolerance checkpoints, we analyzed healthy individuals and CVID patients carrying one or two TACI mutations. We found that TACI interacts with the cleaved, mature forms of TLR7 and TLR9 and plays an important role during B cell activation and the central removal of autoreactive B cells in healthy donors and CVID patients. However, only subjects with a single TACI mutation displayed a breached immune tolerance and secreted antinuclear antibodies (ANAs). These antibodies were associated with the presence of circulating B cell lymphoma 6–expressing T follicular helper (Tfh) cells, likely stimulating autoreactive B cells. Thus, TACI mutations may favor CVID by altering B cell activation with coincident impairment of central B cell tolerance, whereas residual B cell responsiveness in patients with one, but not two, TACI mutations enables autoimmune complications. PMID:24051380

Anti-telomere antibodies in systemic lupus erythematosus (SLE): a comparison with five antinuclear antibody assays in 430 patients with SLE and other rheumatic diseases.

PubMed

Salonen, E M; Miettinen, A; Walle, T K; Koskenmies, S; Kere, J; Julkunen, H

2004-10-01

To investigate the prevalence and diagnostic significance of antibodies against telomeric DNA in systemic lupus erythematosus (SLE) and other autoimmune rheumatic diseases, and to make comparisons with five conventional anti-DNA or anti-nuclear antibody (ANA) assays. Antibodies to telomeres, which are highly repetitive sequences of DNA (TTAGGG/CCCTAA) at the end of eukaryotic chromosomes, were measured by an enzyme linked immunosorbent assay (ELISA) in 305 patients with SLE and 125 patients with other autoimmune rheumatic diseases (78 rheumatoid arthritis, 32 primary Sjögren's syndrome, eight mixed connective tissue disease, seven miscellaneous rheumatic diseases). Other assays used were two commercial ELISA assays for anti-dsDNA using calf thymus as antigen, Crithidialuciliae immunofluorescence, and radioimmunoassay (RIA) for anti-dsDNA and immunofluorescence using Hep-2 cells for ANA. The prevalence of anti-telomere in SLE was 60%, v 5% in rheumatoid arthritis and 18% in other autoimmune rheumatic diseases. Specificity of anti-telomere for SLE was 91%; positive and negative predictive values were 95% and 46%, respectively. For anti-dsDNA by two ELISA assays using calf thymus as antigen, sensitivities were 69% and 29% and specificities 66% and 96%, respectively. Other anti-dsDNA assays had low sensitivities (RIA 43%, Crithidia immunofluorescence 13%). The association of anti-telomere with a history of nephritis in patients with SLE was stronger (p = 0.005) than by any other assay (p = 0.006-0.999). The correlations between the different assays were good (p<0.001 for all comparisons). The new ELISA for anti-telomere antibodies using standardised human dsDNA as antigen is a sensitive and highly specific test for SLE.

Molecular Basis of 9G4 B Cell Autoreactivity in Human Systemic Lupus Erythematosus

PubMed Central

Richardson, Christopher; Chida, Asiya Seema; Adlowitz, Diana; Silver, Lin; Fox, Erin; Jenks, Scott A.; Palmer, Elise; Wang, Youliang; Heimburg-Molinaro, Jamie; Li, Quan-Zhen; Mohan, Chandra; Cummings, Richard; Tipton, Christopher

2013-01-01

9G4+ IgG Abs expand in systemic lupus erythematosus (SLE) in a disease-specific fashion and react with different lupus Ags including B cell Ags and apoptotic cells. Their shared use of VH4-34 represents a unique system to understand the molecular basis of lupus autoreactivity. In this study, a large panel of recombinant 9G4+ mAbs from single naive and memory cells was generated and tested against B cells, apoptotic cells, and other Ags. Mutagenesis eliminated the framework-1 hydrophobic patch (HP) responsible for the 9G4 idiotype. The expression of the HP in unselected VH4-34 cells was assessed by deep sequencing. We found that 9G4 Abs recognize several Ags following two distinct structural patterns. B cell binding is dependent on the HP, whereas anti-nuclear Abs, apoptotic cells, and dsDNA binding are HP independent and correlate with positively charged H chain third CDR. The majority of mutated VH4-34 memory cells retain the HP, thereby suggesting selection by Ags that require this germline structure. Our findings show that the germline-encoded HP is compulsory for the anti–B cell reactivity largely associated with 9G4 Abs in SLE but is not required for reactivity against apoptotic cells, dsDNA, chromatin, anti-nuclear Abs, or cardiolipin. Given that the lupus memory compartment contains a majority of HP+ VH4-34 cells but decreased B cell reactivity, additional HP-dependent Ags must participate in the selection of this compartment. This study represents the first analysis, to our knowledge, of VH-restricted autoreactive B cells specifically expanded in SLE and provides the foundation to understand the antigenic forces at play in this disease. PMID:24108696

Aging-dependent decline of IL-10 producing B cells coincides with production of antinuclear antibodies but not rheumatoid factors.

PubMed

van der Geest, Kornelis S M; Lorencetti, Pedro G; Abdulahad, Wayel H; Horst, Gerda; Huitema, Minke; Roozendaal, Caroline; Kroesen, Bart-Jan; Brouwer, Elisabeth; Boots, Annemieke M H

2016-03-01

Aging is associated with development of autoimmunity. Loss of B cell tolerance in the elderly is suggested by an increased prevalence of anti-nuclear antibodies (ANAs) and rheumatoid factors (RFs). Accumulating evidence indicates that B cells also impact autoimmunity via secretion of cytokines. So far, few studies have directly assessed the effect of aging on the latter B cell function. Here, we determined if and how human aging influences the production of cytokines by B cells. In a cross-sectional study, we found that absolute numbers of circulating B cells were similar in 31 young (ages 19-39) and 73 old (age ≥ 60) individuals. Numbers of transitional B cells (CD19(+)CD27(-)CD38(High)CD24(High)) were decreased in old individuals, whereas numbers of naive and memory B cell subsets were comparable in young and old individuals. Short-term in vitro stimulation of whole blood samples revealed that numbers of B cells capable of producing TNF-α were similar in young and old individuals. In contrast, B cells capable of IL-10 production were decreased in old subjects. This decline of IL-10(+) B cells was observed in old individuals that were ANA positive, and in those that were negative for both ANAs and RFs. However, IL-10(+) B cells were remarkably well retained in the circulation of old subjects that were RF positive. Thus, pro-inflammatory TNF-α(+) B cells are retained in the elderly, whereas IL-10(+) B cells generally decline. In addition, our findings indicate that IL-10(+) B cells may differentially impact the development of ANAs and RFs in the elderly. Copyright © 2015 Elsevier Inc. All rights reserved.

Markers of autoimmune liver diseases in postmenopausal women with osteoporosis

PubMed Central

Demirdal, Umit Secil; Ciftci, Ihsan Hakkı; Kavuncu, Vural

2010-01-01

INTRODUCTION: Osteoporosis is a common complication of chronic liver diseases. However, there is limited information about autoimmune liver diseases as a factor of secondary osteoporosis. Therefore, we aimed to investigate the autoantibodies of autoimmune liver diseases in patients with osteoporosis. METHODS: One hundred fifty female patients with postmenopausal osteoporosis were included. Bone mineral density was measured by dual energy X‐ray absorptiometry. We analysized autoantibodies including antinuclear antibodies, liver membrane antibodies, anti‐liver/kidney microsomal autoantibodies1, liver‐specific protein, anti‐smooth muscle antibodies, and anti‐mitochondrial antibodies by indirect immunofluorescence. Serum was assayed for the levels of aminotransferases. RESULTS: The mean age of the patients was 63,13±8,6 years. The mean values of L1‐L4 T‐scores and femur total T‐scores were ‐3,08±0,58 and ‐1,53±0,81, respectively. Among the 150 patients with osteoporosis, 14 (9.3%) were antinuclear antibodies, four (2.7%) were liver membrane antibodies, three (2.0%) were anti‐liver/kidney microsomal autoantibodies1, and two (1.3%) were liver‐specific protein positive. None of the patients had anti‐mitochondrial antibodies or smooth muscle antibodies positivity. The mean values of levels of aminotransferases were within normal range. CONCLUSIONS: The presence of liver membrane antibodies, liver‐specific protein, and anti‐liver/kidney microsomal autoantibodies1 has permitted us to see that there may be some suspicious clues of autoimmune liver diseases in patients with osteoporosis as a secondary risk factor. On the other hand, there is a need for comprehensive studies with a larger sample size and studies designed to compare the results with a normal population to understand the clinical importance of our findings. PMID:21120296

Mercury exposure, serum antinuclear/antinucleolar antibodies, and serum cytokine levels in mining populations in Amazonian Brazil: a cross-sectional study.

PubMed

Gardner, Renee M; Nyland, Jennifer F; Silva, Ines A; Ventura, Ana Maria; de Souza, Jose Maria; Silbergeld, Ellen K

2010-05-01

Mercury is an immunotoxic substance that has been shown to induce autoimmune disease in rodent models, characterized by lymphoproliferation, overproduction of immunoglobulin (IgG and IgE), and high circulating levels of auto-antibodies directed at antigens located in the nucleus (antinuclear auto-antibodies, or ANA) or the nucleolus (antinucleolar auto-antibodies, or ANoA). We have reported elevated levels of ANA and ANoA in human populations exposed to mercury in artisanal gold mining, though other confounding variables that may also modulate ANA/ANoA levels were not well controlled. The goal of this study is to specifically test whether occupational and environmental conditions (other than mercury exposure) that are associated with artisanal gold mining affect the prevalence of markers of autoimmune dysfunction. We measured ANA, ANoA, and cytokine concentrations in serum and compared results from mercury-exposed artisanal gold miners to those from diamond and emerald miners working under similar conditions and with similar socio-economic status and risks of infectious disease. Mercury-exposed gold miners had higher prevalence of detectable ANA and ANoA and higher titers of ANA and ANoA as compared to diamond and emerald miners with no occupational mercury exposure. Also, mercury-exposed gold miners with detectable ANA or ANoA in serum had significantly higher concentrations of pro-inflammatory cytokines IL-1beta, TNF-alpha, and IFN-gamma in serum as compared to the diamond and emerald miners. This study provides further evidence that mercury exposure may lead to autoimmune dysfunction and systemic inflammation in affected populations. Copyright 2010 Elsevier Inc. All rights reserved.

Autoimmunity and glomerulonephritis in mice with targeted deletion of the serum amyloid P component gene: SAP deficiency or strain combination?

PubMed Central

Gillmore, Julian D; Hutchinson, Winston L; Herbert, Jeff; Bybee, Alison; Mitchell, Daniel A; Hasserjian, Robert P; Yamamura, Ken-Ichi; Suzuki, Misao; Sabin, Caroline A; Pepys, Mark B

2004-01-01

Human serum amyloid P component (SAP) binds avidly to DNA, chromatin and apoptotic cells in vitro and in vivo. 129\\Sv × C57BL\\6 mice with targeted deletion of the SAP gene spontaneously develop antinuclear autoantibodies and immune complex glomerulonephritis. SAP-deficient animals, created by backcrossing the 129\\Sv SAP gene deletion into pure line C57BL\\6 mice and studied here for the first time, also spontaneously developed broad spectrum antinuclear autoimmunity and proliferative immune complex glomerulonephritis but without proteinuria, renal failure, or increased morbidity or mortality. Mice hemizygous for the SAP gene deletion had an intermediate autoimmune phenotype. Injected apoptotic cells and isolated chromatin were more immunogenic in SAP–\\– mice than in wild-type mice. In contrast, SAP-deficient pure line 129\\Sv mice did not produce significant autoantibodies either spontaneously or when immunized with extrinsic chromatin or apoptotic cells, indicating that loss of tolerance is markedly strain dependent. However, SAP deficiency in C57BL\\6 mice only marginally affected plasma clearance of exogenous chromatin and had no effect on distribution of exogenous nucleosomes between the liver and kidneys, which were the only tissue sites of catabolism. Furthermore, transgenic expression of human SAP in the C57BL\\6 SAP knockout mice did not abrogate the autoimmune phenotype. This may reflect the different binding affinities of mouse and human SAP for nuclear autoantigens and\\or the heterologous nature of transgenic human SAP in the mouse. Alternatively, the autoimmunity may be independent of SAP deficiency and caused by expression of 129\\Sv chromosome 1 genes in the C57BL\\6 background. PMID:15147569

Measurement of Antinuclear Antibodies: Assessment of Different Test Systems

PubMed Central

Kern, P.; Kron, M.; Hiesche, K.

2000-01-01

The performance of rat liver and HEp-2 in the detection of antinuclear antibodies (ANA) was studied by two independent sites and compared against an ANA enzyme immunoassay (EIA) screen and EIA systems for the measurement of antibodies to double-stranded DNA (dsDNA) and ENA. Sixty-two sera from patients with connective tissue disease (CTD) and 398 from controls suffering from other disorders were included. The level of agreement was, for HEp-2 and rat liver (within one site), 82.0% (ANA positive/ANA negative) and 51.0% (ANA pattern); and for HEp2- and HEp-2 (between sites), 71.8 and 86.5%. On sera with the ANA homogeneous pattern, the measurement of anti-ENA EIA added little to the detection rate with anti-dsDNA EIA alone. On ANA speckled sera, the EIA reactivity depended on the reaction of the mitotic cells: while sera with positive mitoses reacted similarly to ANA homogeneous sera, in those with negative mitoses the measurement of anti-ENA added about 10% to the detection rate achieved with anti-dsDNA alone. The measurement of anti-Scl-70 and anti-Jo-1 did not markedly improve the positive rate with classical ENA (anti-SSA, -SSB, -Sm, and -RNP) alone, raising doubts about the cost efficiency of including these measurements in unselected sera. The ANA EIA identified patients with CTD at a rate similar to that for rat liver and HEp-2. However, up to 98% of the sera found to be negative by ANA EIA but positive by use of rat liver and HEp-2 were from controls. Thus, the ANA EIA may possible be used as an alternative screen, particularly in laboratories with a high frequency of sera from patients not suffering from CTD. PMID:10618281

Characterization of a spontaneous disease of white leghorn chickens resembling progressive systemic sclerosis (scleroderma)

PubMed Central

1981-01-01

University of California, Davis (UCD) line 200 White Leghorn Chickens spontaneously develop a syndrome that has many analogous features to human progressive systemic sclerosis. This syndrome is characterized by progressive involution of comb, dermal fibrosis, and distal polyarthritis. These three features occur within 6 wk after hatching, and are accompanied by a 40% mortality as a result of vaso-occlusive disease, with development of secondary infection of peripheral gangrenous lesions. Birds that survive greater than 2 mo after hatching progressively develop fibrosis of the esophagous and mononuclear infiltration of heart and kidney, with prominent occlusion of small and medium sized blood vessels. In addition, line 200 chickens develop rheumatoid factors, antinuclear antibodies, and antibodies to collagen, but do not have antibodies to thymocytes, DNA, or extractable nuclear antigens. Moreover, antinuclear antibodies when studied using HEp-2 cells as substrate demonstrate predominantly a speckled pattern. This syndrome of line 200 chickens is not detectable in F1 crosses to several UCD inbred lines. F1 X parental line BC1 backcrosses have an approximately 50% incidence of disease, suggesting that this syndrome is inherited as autosomal recessive. However, only 4% of F2 generation birds show abnormal symptoms, suggesting the presence of modifying genes. There is no appearance of IgG deposition, as determined by immunofluorescence, in either skin, blood vessels, esophagus, or heart. However, approximately 20% of chickens have a glomerulonephritis; this feature appears to be a terminal event and does not appear clinically significant. Although this syndrome of line 200 chickens has several features that are in sharp distinction to human scleroderma, the presence of common immunologic and pathologic denominators suggest that this spontaneous disease may be an appropriate model to develop a better understanding of autoimmune connective tissue diseases. PMID:7252423

Reproductive and hormonal risk factors for antinuclear antibodies (ANA) in a representative sample of U.S. women

PubMed Central

Parks, Christine G.; Miller, Frederick W.; Satoh, Minoru; Chan, Edward K.L.; Andrushchenko, Zhanna; Birnbaum, Linda S.; Jusko, Todd A.; Kissling, Grace E.; Patel, Mehul D.; Rose, Kathryn M.; Weinberg, Clarice; Zeldin, Darryl C.; Sandler, Dale P.

2014-01-01

Background Autoantibodies are of growing interest in cancer research as potential biomarkers; yet the determinants of autoimmunity are not well understood. Antinuclear antibodies (ANA) are common in the general population, and are more prevalent in women and older adults. Here we examined the relationship of ANA with reproductive and hormonal factors in a representative sample of U.S. women. Methods We analyzed data on reproductive history and exogenous hormone use in relation to serum ANA in 2,037 females ages 12 and older from the National Health and Nutrition Examination Survey (NHANES; 1999–2004). Estimated ANA prevalences were adjusted for sampling weights. Prevalence odds ratios (POR) and 95% confidence intervals (CI) were adjusted for age, race and poverty-income-ratio, and models were stratified by menopause status. Results In premenopausal women ages 20 and older, ANA prevalence was associated with parity (p<0.001; parous versus nulliparous POR=2.0; 95%CI 1.2, 3.4), but in parous women ANA did not vary by number of births, age at first birth, years since last birth or breastfeeding. In postmenopausal women, ANA prevalence was associated with an older age at menarche (p=0.019; age 16–20 versus 10–12 years POR=3.0, 95%CI 1.6, 5.9), but not with parity. Oral contraceptives and estrogen therapy were not associated with a higher ANA prevalence. Conclusions Childbearing (having had one or more births) may explain age-associated elevations in ANA prevalence seen in premenopausal women. Impact These findings highlight the importance of considering reproductive history in studies of autoimmunity and cancer in women. PMID:25086100

Antibodies against cyclic citrullinated peptides in patients affected by rheumatoid arthritis before and after infliximab treatment.

PubMed

Caramaschi, Paola; Biasi, Domenico; Tonolli, Elisabetta; Pieropan, Sara; Martinelli, Nicola; Carletto, Antonio; Volpe, Alessandro; Bambara, Lisa Maria

2005-11-01

To evaluate antibodies against cyclic citrullinated peptides (anti-CCP) together with rheumatoid factor (RF), antinuclear antibodies (ANA) and C-reactive protein (CRP), in patients affected by rheumatoid arthritis (RA), before and after infliximab treatment. Twenty-seven patients (five men and 22 women, mean age of 51.9 years, mean duration of disease 12.6 years) affected by RA, refractory to conventional DMARDs, were treated with infliximab, at the conventional dosage. Before starting infliximab and after 22 weeks, on the occasion of the fifth infusion, anti-CCP antibodies were tested by ELISA method. At the same time IgM RF, ANA and CRP level were measured. Before infliximab therapy, anti-CCP antibodies resulted positive in 23 patients (85.1%); the serum level did not change after infliximab treatment; only one case negative at baseline became slightly positive after treatment. Before and after therapy RF resulted positive in 22 cases (81.4%) and 21 cases (77.7%) respectively; comparing values at baseline with those after 22 weeks of treatment with infliximab, RF levels significantly decreased, as well as CRP values. In contrast to both anti-CCP antibodies, which remained stable, and to RF, which fell after infliximab, ANA were positive > or = 1: 160 in four cases at baseline and in 12 after treatment. The titre of anti-CCP antibodies did not significantly change after anti-TNFalpha blocker administration; instead the positivity of RF significantly decreased. As opposed to antinuclear and anti-dsDNA antibodies, which may appear or increase in titre during infliximab treatment, the typical autoantibodies detectable in RA show a different trend; in fact, anti-CCP antibodies remained stable and RF decreased.

Antinuclear antibodies in patients with polymorphic light eruption: a long-term follow-up study.

PubMed

Tzaneva, S; Volc-Platzer, B; Kittler, H; Hönigsmann, H; Tanew, A

2008-05-01

Previous studies have shown elevated titres of antinuclear antibodies (ANA) in 2.9-19% of patients with polymorphic light eruption (PLE). A diagnosis of lupus erythematosus (LE) was finally established in some of these ANA-positive patients. To investigate whether the presence of ANA in patients with PLE merely represents an epiphenomenon or is associated with an increased risk of eventual progression to LE. We identified 472 patients with PLE who had received prophylactic photo(chemo)therapy between 1986 and 2003 and were routinely tested for the presence of ANA. All ANA-positive (ANA titre of>or=1:80) patients were asked to attend for a follow-up examination comprising a medical history, complete skin inspection and a detailed laboratory analysis including ANA and antibodies against extractable nuclear antigens. Of all the patients, 55 (11.7%) were found to be ANA positive on one or several occasions, and three (0.6%) also had antibodies to SS-A/Ro. Thirty-nine (71%) of all ANA-positive patients including all Ro+ subjects were available for follow-up after a median follow-up period of 8 years (interquartile range 5-11.5). Twenty-five patients showed persistence of ANA positivity with a median titre of 1:160 (range 1:80-1:640), whereas in 14 patients ANA titres had returned to normal levels. None of the patients revealed additional clinical, histopathological or laboratory abnormalities suggestive of LE. After a median follow-up period of 8 years none of the ANA-positive patients developed LE. Our findings indicate that PLE is a benign disease without tendency to progress to LE.

A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice.

PubMed

Roths, J B; Murphy, E D; Eicher, E M

1984-01-01

A newly discovered autosomal recessive mutation, generalized lymphoproliferative disease (gld), in the C3H/HeJ strain of mice, determines the development of early onset massive lymphoid hyperplasia with autoimmunity. Significant lymph node enlargement is apparent as early as 12 wk of age. By 20 wk, lymph nodes are 50-fold heavier than those of coisogenic C3H/HeJ-+/+ mice. There is a concomitant increase in the numbers of peripheral blood lymphocytes. Analysis of C3H-gld lymph node lymphocyte subsets by immunofluorescence indicates an increase in numbers of B cells, T cells, and null (Thy-1-, sIg-) lymphocytes by 6-, 15-, and 33-fold compared with congeneic control mice. Serologically, gld/gld mice develop antinuclear antibodies (including anti-dsDNA), thymocyte-binding autoantibody, and hypergammaglobulinemia with major increases in several immunoglobulin isotypes. Mutant gld mice live only one-half as long as normal controls (12 and 23 mo, respectively). Interstitial pneumonitis was found in virtually all C3H-gld mice autopsied when moribund. Although immune complexes were detected in the glomerulus by immunofluorescence techniques, only 14% of the autopsied mice had significant lupus-like nephritis. Vascular disease was not found. The pattern of early onset massive lymph node enlargement, hypergammaglobulinemia, and production of antinuclear autoantibodies resembles the basic abnormal phenotype induced by the lpr (lymphoproliferation) mutation. The mutations gld and lpr are not allelic. Linkage studies indicate that gld is located between Pep-3 and Lp on chromosome 1. This new mutation adds another genetically well-defined model to the list of murine lymphoproliferative/autoimmune disorders that may be exploited to gain a clearer understanding of immunoregulatory defects and for identifying common pathogenetic factors involved in systemic autoimmune diseases.

A new mutation, gld, that produces lymphoproliferation and autoimmunity in C3H/HeJ mice

PubMed Central

1984-01-01

A newly discovered autosomal recessive mutation, generalized lymphoproliferative disease (gld), in the C3H/HeJ strain of mice, determines the development of early onset massive lymphoid hyperplasia with autoimmunity. Significant lymph node enlargement is apparent as early as 12 wk of age. By 20 wk, lymph nodes are 50-fold heavier than those of coisogenic C3H/HeJ-+/+ mice. There is a concomitant increase in the numbers of peripheral blood lymphocytes. Analysis of C3H-gld lymph node lymphocyte subsets by immunofluorescence indicates an increase in numbers of B cells, T cells, and null (Thy-1-, sIg-) lymphocytes by 6-, 15-, and 33-fold compared with congeneic control mice. Serologically, gld/gld mice develop antinuclear antibodies (including anti-dsDNA), thymocyte-binding autoantibody, and hypergammaglobulinemia with major increases in several immunoglobulin isotypes. Mutant gld mice live only one-half as long as normal controls (12 and 23 mo, respectively). Interstitial pneumonitis was found in virtually all C3H-gld mice autopsied when moribund. Although immune complexes were detected in the glomerulus by immunofluorescence techniques, only 14% of the autopsied mice had significant lupus-like nephritis. Vascular disease was not found. The pattern of early onset massive lymph node enlargement, hypergammaglobulinemia, and production of antinuclear autoantibodies resembles the basic abnormal phenotype induced by the lpr (lymphoproliferation) mutation. The mutations gld and lpr are not allelic. Linkage studies indicate that gld is located between Pep-3 and Lp on chromosome 1. This new mutation adds another genetically well-defined model to the list of murine lymphoproliferative/autoimmune disorders that may be exploited to gain a clearer understanding of immunoregulatory defects and for identifying common pathogenetic factors involved in systemic autoimmune diseases. PMID:6693832

Emerging technologies in autoantibody testing for rheumatic diseases.

PubMed

Olsen, Nancy J; Choi, May Y; Fritzler, Marvin J

2017-07-24

Testing for the presence of antinuclear antibodies (ANAs) is a key step in the diagnosis of systemic lupus erythematosus (SLE) and other systemic autoimmune rheumatic diseases (SARD). The standard slide-based indirect immunofluorescence (IIF) test is widely used, but is limited by a relative lack of specificity for SLE and not all SARD-ANAs are detected. Alternative immunoassays that might offer enhanced diagnostic and prognostic information have evolved, and some of these have entered clinical practice. This review summarizes the current state of ANA testing and multiplex techniques for detecting other autoantibodies, the possibility of point-of-care testing, and approaches for applications in early disease stages.

The Child as a Surrogate for Diagnosis of Lupus in the Mother.

PubMed

Adelowo, Olufemi O; Ohagwu, Kenneth A; Aigbokhan, Ejiehi E; Akintayo, Richard O

2017-01-01

Introduction. Neonatal lupus erythematosus (NLE) is an acquired disease of the newborn caused by transplacental transfer of maternal anti-Ro/SSA, anti-La/SSB, and infrequently anti-U1 RNP antibodies. Methodology. This is a case report of a male infant delivered via Caesarean section at 36-week gestation following detection of fetal bradycardia during routine antenatal clinic visit. Results. The mother was seropositive for antinuclear antibody (ANA) and anti-Ro/SSA and had elevated erythrocyte sedimentation rate. The baby was positive for ANA, extractable nuclear antigen (ENA), and anti-Ro/SSA. Pediatric echocardiography was abnormal and electrocardiography confirmed complete heart block.

Prevalence of autoantibodies against cellular antigens in patients with HIV and leprosy coinfection in the Amazon region.

PubMed

Bichara, Clea Nazaré Carneiro; Bichara, Carlos David Araújo; Tostes, Camila; Povoa, Marinete Marins; Quaresma, Juarez Antonio Simões; Xavier, Marília Brasil

2017-06-01

Infectious agents can activate self-reactive T cells. In general, infections trigger various mechanisms, including a lack of auto-tolerance, induction of costimulatory molecules on antigen presenting cells, and molecular simulation, in addition to cross-reactions between microbial antigens and self-antigens. HIV and leprosy coinfections lead to self-immunity with the production of autoantibodies. However, not enough data on the immune behaviour associated with this coinfection are available. Therefore, this study focused on the detection of autoantibodies against cellular antigens (AACA) in individuals with HIV and leprosy coinfection in the Amazon region. Patients were distributed into four groups according to their infections: (i) coinfection with HIV and leprosy (n = 23), (ii) infection with leprosy (n = 33), (iii) infection with HIV/AIDS (n = 25), and (iv) healthy blood donor controls (n = 100). AACA were identified by indirect immunofluorescence and the samples were tested using a commercial diagnosis kit containing the antinuclear antibody HEp-2. Morphologically, all stages of cell division were assessed in addition to the morphological features associated with the nuclear matrix, nucleolus, mitotic spindle, and cytoplasm. There was a high prevalence of AACA in the coinfection group (47.8%, n = 11) when compared with the control group of healthy blood donors (2.0%). The results showed predominantly cytoplasmic staining in all groups analysed, and no difference was observed between the presence or absence of AACA and the leprosy forms (paucibacillary and multibacillary) in the coinfection group. The results of this study show that despite the tendency of coinfected patients to have higher levels of autoantibodies, no correlation was observed between clinical and laboratorial variables and morbidity associated with HIV and leprosy coinfections or the levels of AACA in the serum of coinfected patients. These data are important to elucidate this complex relationship between HIV and leprosy and thus improve the follow-up of these patients.

Similarities and differences between older and young adult patients with celiac disease.

PubMed

Kalkan, Çağdaş; Karakaya, Fatih; Soykan, Irfan

2017-11-01

Celiac disease is an autoimmune enteropathy with variable clinical symptoms. Elderly patients can have different manifestations from those of young patients. The aims of the present study were to investigate whether any differences or similarities exist between older and young patients with celiac disease with a special emphasis on concurrent autoimmune diseases. Celiac disease patients were stratified as older and younger patients. These two groups were then compared by means of clinical symptoms, laboratory parameters and concurrent autoimmune diseases. Factors associated with the presence of an autoimmune disease were identified by univariate and multivariate analysis. There were 66 older patients (mean age 67.7 ± 3.2 years, 50 women), and 277 younger patients (mean age 35.9 ± 11.7 years, 207 women). Of the 66 older patients, eight patients had gastrointestinal symptoms and 58 patients had extradigestive symptoms. In the younger group, the number of patients referred due to gastrointestinal symptoms was higher (8 [12.2%] vs 200 (72.2%), P < 0.001) compared with the older group. Whereas 10 (15.1%) older patients showed polyautoimmunity, 55 (19.8%) younger patients had polyautoimmunity. Multiple autoimmune syndrome was more common in older patients compared with young patients (31 [47%] vs 12 [4%], P < 0.001, respectively). The presentation of celiac disease clinically, histologically and by means of laboratory parameters is different in older and young patients. Polyautoimmunity and multiple autoimmune syndrome are more common in older patients compared with younger patients. A biopsy score of Marsh score type, antinuclear antibody positivity, high serum anti-tissue transglutaminase immunoglobulin A level and low hemoglobin level were risk factors for having an autoimmune disease. Geriatr Gerontol Int 2017; 17: 2060-2067. © 2017 Japan Geriatrics Society.

Autoimmune hepatitis in children: progression of 20 cases in northern Mexico.

PubMed

Nares-Cisneros, J; Jaramillo-Rodríguez, Y

2014-01-01

Autoimmune hepatitis (AIH) is a chronic inflammatory disease of the liver with nonspecific clinical manifestations that causes greater liver damage in children than in adults. To analyze the clinical progression, biochemical profiles, histopathologic changes, and treatment response in 20 children with AIH. A retrospective study was carried out on the variables associated with clinical progression, diagnosis, and treatment response in children seen at the the Unidad Médica de Alta Especialidad (UMAE) No. 71 IMSS in Torreón, Coahuila, Mexico, from 1992 to 2012. Twenty patients were analyzed, 75% with type 1 AIH (AIH-1) and 25% with type 2 AIH (AIH-2). Girls predominated with a 3:1 ratio of girls to boys. The mean age was 10.07 ± 6.53 years for the AIH-1 cases and 6.75 ± 3.77 years for the AIH-2 cases. There was an association with immunologic diseases in 40% of the patients. The patients in the AIH-2 group had greater biochemical profile alterations and IgA deficiency. Anti-nuclear antibody and anti-smooth muscle antibody were positive in 100% of the patients with AIH-1, and anti-liver kidney microsomal type 1 antibody was positive in 100% of the AIH-2 patients. Liver biopsy revealed interface hepatitis in both groups. The AIH-2 group responded more quickly to treatment, but had a higher recurrence rate. Autoimmune hepatitis in the pediatric patient should be suspected in order to make an early diagnosis and thereby establish opportune treatment. Determining the type of AIH is necessary for making adequate diagnosis and for achieving a better outcome in relation to recurrence and complication rates. Copyright © 2014 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

A Korean rheumatic diseases screening questionnaire.

PubMed Central

Lee, Hye-Soon; Oh, Kwang-Taek; Kim, Tae-Hwan; Jung, Sungsoo; Yoo, Dae-Hyun; Bae, Sang-Cheol

2003-01-01

The aim of our study was to develop a Korean rheumatic diseases-screening questionnaire. The questionnaire was constructed based on American College of Rheumatology criteria for rheumatic diseases and a connective tissue diseases screening questionnaire. Two groups of patients were selected and completed the questionnaire: (i) those with osteoarthritis (n=46), rheumatoid arthritis (n=52), systemic lupus erythematosus (n=50), scleroderma (n=8), polymyositis or dermatomyositis (n=7), Sjogren's disease (n=4), and mixed connective-tissue disease (n=9) as case subjects; and (ii) those with fibromyalgia (n=8) and general disease without evidence of any rheumatic disease (n=72) as controls. Laboratory results were analyzed for correlation with actual data using kappa (kappa) statistics. Test-retest reliability was performed in 12 patients, and showed strong agreement between the first and second interviews (kappa=0.91). The sensitivity of the questionnaire ranged from 77.8 to 100%, and specificity ranged from 68.8 to 95.0%. Negative predictive values were very high in the general population, from 98.4 to 99.99%. The kappa statistic for agreement between laboratory items was 0.22-0.56, except for rheumatoid factor, antinuclear antibody test, and muscle enzyme level. We have developed a simple and sensitive Korean rheumatic diseases-screening questionnaire for the epidemiologic study of rheumatic diseases in Korea. PMID:12692412

Autoimmune hepatitis.

PubMed

Vergani, D; Mieli-Vergani, G

2004-06-01

Autoimmune hepatitis (AIH) is characterised histologically by interface hepatitis, and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G. Its onset is often ill-defined, frequently mimicing acute hepatitis. AIH usually responds to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Two types of AIH are recognized according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1 AIH) or liver kidney microsomal type 1 antibody (LKM1, type 2 AIH). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age and commonly have immunoglobulin A deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in the 2 groups. Susceptibility to AIH type 1 is conferred by possession of HLA DR3 and DR4, while to AIH type 2 by possession of HLA DR7. Liver damage is likely to derive from an immune reaction to liver cell antigens, possibly triggered by a mechanism of molecular mimicry, where immune responses to external pathogens, e.g. viruses, become directed towards structurally similar self-components. In AIH this process would be perpetuated by impairment in immune regulation.

[Antibodies and physiopathogeny of autoimmune hepatitis].

PubMed

García-Leiva, Jorge; Ríos-Vaca, Aurelio; Torre-Delgadillo, Aldo

2003-01-01

Autoimmune hepatitis (AIH) is an inflammatory disease of unknown cause characterized by periportal hepatitis, increased serum globulins and the presence of certain antibodies. The disorder can be classified in three types. Type 1 AIH is characterized by the presence of antinuclear antibodies (ANA) and smooth muscle autoantibodies (SMA) in up to 70-80% of patients. ANA and SMA can be the only antibodies present in 13 and 33% of cases respectively. Type 2 AIH is defined by the presence of liver and kidney antimicrosomal antibodies (LKM1). Type 2 AIH is the only form of the disease in which the autoantigen has been identified: cytochrome mono-oxygenase (P-450 IID6) CYP2D6. In type 3 AIH the presence of anti-SLA/LP (soluble liver antigen/liver pancreas) targets a cytosolic protein involved in the incorporation of selenocysteine into peptidic chains. The pathophysiology of AIH is complex and involves genetic predisposition, previous exposure to antigens (autoantigens), presence of triggering factors and defects in immunoregulation. In spite of the advances in the understanding of AIH, the role of autoantibodies in the pathophysiology of this disease has not been fully established and their presence does not clearly distinguish any prognostic groups. Further investigations will help in the diagnosis of this disorder, the comprehension of its origins and the establishment of new forms of treatment.

Choosing Wisely: the American College of Rheumatology's Top 5 for pediatric rheumatology.

PubMed

Rouster-Stevens, Kelly A; Ardoin, Stacy P; Cooper, Ashley M; Becker, Mara L; Dragone, Leonard L; Huttenlocher, Anna; Jones, Karla B; Kolba, Karen S; Moorthy, L Nandini; Nigrovic, Peter A; Stinson, Jennifer N; Ferguson, Polly J

2014-05-01

To create a pediatric rheumatology Top 5 list as part of the American Board of Internal Medicine Foundation's Choosing Wisely campaign. Delphi surveys of a core group of representative pediatric rheumatology providers from across North America generated candidate Top 5 items. Items with high content agreement and perceived to be of prevalent use and of high impact were included in a survey of all American College of Rheumatology (ACR) members who identified themselves as providing care to pediatric patients. Items with the highest ratings were subjected to literature review and further evaluation. A total of 121 candidate items were proposed in the initial Delphi survey and were reduced to 28 items in subsequent surveys. These 28 items were sent to 1,198 rheumatology providers who care for pediatric patients, and 397 (33%) responded. Based upon survey data and literature review, the Top 5 items were identified. These items focused on testing for antinuclear antibodies, autoantibody panels, Lyme disease, methotrexate toxicity monitoring, and use of routine radiographs. The ACR pediatric rheumatology Top 5 is one of the first pediatric subspecialty-specific Choosing Wisely Top 5 lists and provides an opportunity for patients and providers to discuss appropriate use of health care in pediatric rheumatology. Copyright © 2014 by the American College of Rheumatology.

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry.

PubMed

Denton, Christopher P; Krieg, Thomas; Guillevin, Loic; Schwierin, Barbara; Rosenberg, Daniel; Silkey, Mariabeth; Zultak, Maurice; Matucci-Cerinic, Marco

2012-05-01

The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies.

The clinical spectrum of remitting seronegative symmetrical synovitis with pitting edema. The Catalán Group for the Study of RS3PE.

PubMed

Olivé, A; del Blanco, J; Pons, M; Vaquero, M; Tena, X

1997-02-01

To describe the clinical and laboratory features and outcome of patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE). A retrospective multicenter study of patients with RS3PE fulfilling the following criteria: (1) bilateral pitting edema of both hands, (2) sudden onset of polyarthritis, (3) age > 50 years, (4) seronegative for rheumatoid factor (RF). 27 patients with RS3PE were included, mean age 71.7 years (58-92), 18 men (66.6%) and 9 women (33.3%). Relevant history was noted in 2 patients with polymyalgia rheumatica. Main clinical features were polyarthritis and edema of both hands. Polyarthritis involved metacarpophalangeal joints in 22 patients (81.5%), proximal interphalangeal joints in 19 (70.4%), wrists in 15 (55.5%), shoulders in 13 (48%), elbows in 3 (11.1%), knees in 9 (33.3%), and ankles in 7 (25.9%). All patients were RF negative. Antinuclear antibodies were positive at low titer in 8 patients. Erosions were present in one patient. Two patients developed T lymphoma and one myelodysplastic syndrome. RS3PE is a heterogeneous syndrome the clinical history, presence of erosions, and evolution to hematological diseases in our patients suggest that RS3PE may not be a distinct clinical entity.

[Sjögren syndrome in ORL. Diagnostic considerations].

PubMed

Leache Pueyo, J J; Sevil Navarro, J; Del Agua, C

2001-01-01

A presentation the history of a 51-year-old woman with xerostomia and keratoconjunctivitis sicca (KCS), developed in 10 months, investigations revealed the presence in serum of antibodies against cytoplasmic antigens SS-A (Ac anti-Ro/SS-A), antinuclear antibodies (ANAs) and rheumatoid factor (RF). The Rose Bengal test was positive and in the salivary gammagraphy, made with pertecnate 99 mTc, it was observed a decrease of the captation and excretion of the designer for salivary glands. The histopathology and immunohistochemical study of minor salivary glands showed the presence of a focal lymphocitic sialadenitis (fsa) and a predominance of lymphocites CD4+. It was diagnosed as primary Sjögren's syndrome (PSS) and the patient treated with salivary substitutes, artificial tears and corticoids. We analyse the current diagnostic criteria of the group of study of the European Community for the Sjögren's syndrome (SS) and emphasize the importance of histologic and immunochemical studies, that together with the rest of complementary tests will led us to distinguish not only the different forms of the presentation of the illness but also those of all patients with pathologies which are nowadays very prevalent in our environment, such as the hepatitis C (HCV) an the human immune deficiency (HIV) virus infections.

South Australian Scleroderma Register: analysis of deceased patients.

PubMed

Bond, C; Pile, K D; McNeil, J D; Ahern, M J; Smith, M D; Cleland, L G; Roberts-Thomson, P J

1998-11-01

The demographic, clinical, pathological and serological features of 123 decreased patients with systemic sclerosis have been analysed. These patients consisted of all identified patients dying with this disease in South Australia between 1983 and 1996 inclusive. There were 85 females and 38 males, with the ratio of limited:diffuse:overlap disease subset being 9:5:1. Disease characteristics revealed that patients with the limited disease tended to be female with high frequencies of the centromere autoantibody, while patients with the diffuse disease had equal gender representation with the frequent presence of nucleolar, speckled or homogeneous antinuclear antibody. Mean duration of disease and mean age of death for the limited:diffuse:overlap subsets differed significantly between groups (p < 0.05) and were 16.5, 9.3 and 10.9 years and 71.9, 57.8 and 52.8 years respectively. Cumulative survival curves for the subsets differed highly significantly, with patients with the limited diseases dying more commonly from right heart failure (documented terminally in 25% of the centromere positive limited subset), cardiovascular disease or cancer, while patients with the diffuse subset died from respiratory failure, renal failure or cardiovascular disease. In conclusion, this retrospective analysis has revealed that scleroderma is a relatively common but clinically heterogeneous disorder. There are important clinical and prognostic implications in defining limited versus diffuse versus overlap disease.

47,XXX in an adolescent with premature ovarian failure and autoimmune disease.

PubMed

Holland, C M

2001-05-01

Premature ovarian failure (POF) may be idiopathic or may be associated with genetic or autoimmune disorders. The 47,XXX karyotype has been associated with POF and other genitourinary anomalies. A 17-year-old woman with a history of immune thrombocytopenic purpura was referred to the adolescent medicine clinic for evaluation of oligomenorrhea with secondary amenorrhea. Evaluation revealed hypergonadotrophic premature ovarian failure, a positive antinuclear antibody, and the 47,XXX karyotype. She has since developed a positive anti-cardiolipin antibody but does not meet diagnostic criteria for systemic lupus erythematosis. The presence of known autoimmune disease in a woman with POF should not dissuade the clinician from evaluating for a potential genetic cause.

Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome in a Chronic Hemodialysis Patient

PubMed Central

Yamada, Shunsuke; Fuyuno, Seiya; Eriguchi, Masahiro; Tsuruya, Kazuhiko; Kitazono, Takanari

2012-01-01

A 75-year-old male who was undergoing chronic hemodialysis developed abrupt-onset pitting edema and pain in the dorsum of both hands and feet. Biochemical analysis disclosed increased C-reactive protein, and negative rheumatoid factor and antinuclear antibody. Radiological examination showed no bony erosion. Computed tomography and gallium scintigraphy revealed no active infection or neoplasms. The clinical diagnosis was remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. The pitting edema and inflammatory response quickly subsided after low-dose prednisolone therapy. This case demonstrates that RS3PE syndrome could be a differential diagnosis in elderly patients undergoing dialysis who develop pitting edema and joint pain. PMID:22431931

Dermatomyositis and myastenia gravis: An uncommon association with therapeutic implications.

PubMed

Sangüesa Gómez, Clara; Flores Robles, Bryan Josué; Méndez Perles, Clara; Barbadillo, Carmen; Godoy, Hildegarda; Andréu, José Luis

2015-01-01

The association of dermatomyositis with myasthenia gravis (MG) is uncommon, having been reported so far in only 26 cases. We report the case of a 69 year-old man diagnosed with MG two years ago and currently treated with piridostigmyne. The patient developed acute proximal weakness, shoulder pain and elevated creatine-kinase (CK). He also developed generalized facial erythema and Gottron's papules. Laboratory tests showed positive antinuclear and anti-Mi2 antibodies. Further analysis confirmed CK levels above 1000 U/l. The clinical management of the patient and the therapeutic implications derived from the coexistence of both entities are discusssed. Copyright © 2014 Elsevier España, S.L.U. All rights reserved.

The Many Faces of Lupus

PubMed Central

El-Gabalawy, Hani

1990-01-01

Systemic lupus erythematosus is a multisystem disorder that presents itself in several different ways. Arthritis, dermatitis, nephritis, and pleuropericarditis are the most common features initially. Various hematologic and neuropsychiatric manifestations are also seen during the course of the disease. Anti-nuclear antibodies are the hallmark of lupus but are nonspecific and detectable in many other disorders. Once the diagnosis is established, the severity of the disease needs to be determined, in particular the extent of major organ involvement. The level of disease activity should be repeatedly estimated using clinical and laboratory parameters. Therapeutic decisions are based on disease severity and activity. Aggressive suppression of major organ inflammation and reduction of long-term toxicity are the main goals of therapy. PMID:21233973

Intravenous immunoglobulin therapy in a patient with lupus serositis and nephritis.

PubMed

Meissner, M; Sherer, Y; Levy, Y; Chwalinska-Sadowska, H; Langevitz, P; Shoenfeld, Y

2000-01-01

The use of intravenous immunoglobulin (IVIg) has been reported as an immunomodulating agent in several autoimmune diseases, including systemic lupus erythematosus (SLE). Herein we report a SLE patient with severe clinical presentation that included pericarditis, pleural effusion, nephrotic range proteinuria, leukopenia, and lymphopenia. The patient received one course of high-dose IVIg (2.8 g/kg body weight), and within a week of post-IVIg therapy, her condition significantly improved. One-month post-IVIg there were decreased proteinuria, elevated leukocytes and lymphocytes count, decrease in antinuclear and anti-dsDNA antibodies, and disappearance of pericarditis and pleuritis. This case demonstrates the efficacy of IVIg in severe SLE with various clinical manifestations.

Presence of hemochromatosis-associated mutations in Hispanic patients with iron overload.

PubMed

Nieves-Santiago, Paul; Cancel, Dilany; Canales, Dialma; Toro, Doris H

2011-09-01

To determine the characteristics of the Puerto Rico Veteran population with iron overload in terms of demographic features, clinical manifestations, and the presence of hereditary hemochromatosis (HH) mutations, and to compare such characteristics in patients with and without HH mutations. A retrospective study was conducted in patients with iron overload (transferrin saturation > or = 45%) who were tested for HH mutations from January 2003 to June 2007. Data collected included age, gender, body mass index, hemoglobin level, platelet count, ferritin level, transferrin saturation, ceruloplasmin, alfa-1 antitrypsin, anti-nuclear antibodies, aspartate aminotransferase, alanine aminotransferase, alfa-fetoprotein, viral hepatitis profile, imaging studies, and comorbid conditions. Patients were grouped according to the results of the commercially available HH DNA mutation analysis as homozygote, heterozygote, compound heterozygote, or negative. 94 patients were studied. Most patients were male (90/94); the mean age was 60 years. Of the study group, 36% (34/94) was found positive for HH mutations. The most common mutation was H63D, which was found in 85% (29/34) of patients; 4 homozygotes and 25 heterozygotes. C282Y mutation was identified in only 12% (4/34) of patients, of which one was homozygote. A compound heterozygote (C282Y/ H63D) was also identified. After analyzing the data for confounding factors, 6 of 29 heterozygotes had no other risk factors for liver disease other than the H63D mutation. The predominance of H63D mutations in our population deserves further investigation since it considerably differs from other studied populations with iron overload in which C282Y is the most common mutation.

Pulmonary Toxicity Study of Lunar and Martian Dust Simulants Intratracheally Instilled in Mice

NASA Technical Reports Server (NTRS)

Lam, Chiu-Wing; James, John T.; Latch, John A.; Holian, A.; McCluskey, R.

2000-01-01

NASA is contemplating sending humans to Mars and the Moon for further exploration. The properties of Hawaiian and Californian volcanic ashes allow them to be used to simulate Martian and lunar dusts, respectively. NASA laboratories use these dust simulants to test performance of hardware destined for Martian or lunar environments. Workers in these test facilities are exposed to low levels of these dusts. The present study was conducted to investigate the toxicity of these dust simulants. Particles of respirable-size ranges of lunar simulant (LS), Martian simulant (MS), TiO2 (negative control) and quartz (positive control) were each intratracheally instilled (saline as vehicle) to groups of 4 mice (C57BL, male, 2-3 month old) at a single treatment of 1 (Hi dose) or 0.1 (Lo dose) mg/mouse. The lungs were harvested at the end of 7 days or 90 days for histopathological examination. Lungs of the LS-Lo groups had no evidence of inflammation, edema or fibrosis. The LS-Hi-7d group had mild to moderate acute inflammation, and neutrophilic and lymphocytic infiltration; the LS-Hi-90d group showed signs of chronic inflammation and some fibrosis. Lungs of the MS-Lo-7d group revealed mild inflammation and neutrophilic and lymphocytic infiltration; the MS-Lo-90d group showed mild fibrosis and particle-laden macrophages (PLM). Lungs of the MS-Hi-7d group demonstrated mild to moderate inflammation and large foci of PLM; the MS-Hi-90d group showed chronic mild to moderate inflammation and fibrosis. To mimic the effects of the oxidative and reactive properties of Martian soil surface, groups of mice were exposed to ozone (3 hour at 0.5 ppm) prior to MS dust instillation. Lung lesions in the MS group were more severe with the pretreatment. The results for the negative and positive controls were consistent with the known pulmonary toxicity of these compounds. The overall severity of toxic insults to the lungs were TiO2

Comparison of Screening Dilution and Automated Reading for Antinuclear Antibody Detection on HEP2 Cells in the Monitoring of Connective Tissue Diseases.

PubMed

Depincé-Berger, Anne E; Moreau, Amelie; Bossy, Virginie; Genin, Christian; Rinaudo, Melanie; Paul, Stephane

2016-09-01

Indirect immunofluorescence plays a major role in the detection of antinuclear antibodies (ANAs) and follow-up of their titers in the context of connective tissue diseases. Given the numerous unfavorable features of the conventional manual reading of HEP2 slides (need of time and expert morphologists for the reading, lack of standardization, subjectivity of the interpretation), the biomedical industry has developed automated techniques of slide preparation and microscope reading. We collected 49 sera beforehand analyzed by the conventional reading of slides. They were prepared again by QUANTA-Lyser(®) and reanalyzed in four different conditions: two dilutions of screening (1/40 and 1/80), two different systems of analysis, NOVA View(®) automated reading (INOVA Diagnostics), then confirmation by the operator, and conventional manual reading by two different qualified operators. The analysis was realized in blind of the first interpretation and clinical diagnosis. The sera were classified in four groups, on the basis of the results of the first analysis: negative sera (titer < 1/160; 11 patients), low positives (titer at 1/160; 18 patients), moderated positives (titers between 1/320 and 1/640; 10 patients), and strong positives (titers between 1/1,280 and 1/2,560; 10 patients). Among the 49 patients, 13 presented a connective tissue disease including 4 systemic scleroderma (SS), 3 rheumatoid arthritis (RA), 2 Goujerot-Sjogren (GS), 2 systemic lupus erythematosus (SLE), 1 polymyositis (PM), 1 Raynaud's syndrome (RS), and 1 CREST syndrome. One patient presented both an SLE and an SS. Regarding the screening dilution, the 1/40 dilution is less specific than the 1/80 dilution for both the systems of analysis (5.6% vs. 16.7% for the manual reading, and 27.8% vs. 50% for the automated reading). It also generates statistically more false positives (P = 0.037 for the conventional analysis and P = 0.003 for the automated system). The automated NOVA View(®) reading of slides allows a gain in specificity for both dilutions, and also statistically less false positives (P = 0.002 at the 1/40 and P = 0.0006 at the 1/80), and detriment of the sensitivity at the highest dilution (84.6% vs. 92.3% with manual reading). Thus, according to our analysis of 49 sera, the automated NOVA View(®) system of reading of slides at the dilution 1/80 seems to be a successful condition for the detection of ANAs on HEP2 cells, close to the significance (P = 0.067). The automated NOVA View(®) reading of slides allows saving time, and an improvement in the standardization. Nevertheless, it requires a confirmation by a qualified operator, to interpret mixed patterns in particular. © 2016 Wiley Periodicals, Inc.

Positivity rates of antithyroid antibody, antinuclear antibody and thyroid peroxidase antibody in different types of vitiligo.

PubMed

Lim, H K; Bae, M I; Jeong, K H; Shin, M K; Lee, M-H

2016-04-01

Vitiligo is associated with various autoimmune disorders, and organ-specific autoantibodies are frequently found in patients with this disorder. Vitiligo is classically divided into segmental vitiligo (SV) and nonsegmental vitiligo (NSV), and it is believed that the pathogenesis differs between these two types. As the NSV type is related to an autoimmune mechanism, autoantibody detection rates are likely to be higher in the NSV type than in the segmental type; however, no comparative studies have been performed. To analyse the rates of autoantibody positivity according to the clinical features in patients with vitiligo. Rates of antithyroid antibody (Tg Ab), antinuclear antibody (ANA) and thyroid peroxidase antibody (TPO Ab) positivity were analysed and compared according to the sex, clinical type and age of onset of 807 patients with vitiligo. There were 106 patients with SV (13.1%) and 701 patients with NSV (86.9%). Tg Ab and ANA positivity did not differ between the SV and NSV types. A positive TPO Ab result was obtained in 16 patients with SV (15.1%) and 173 patients with NSV (24.7%). The TPO Ab positivity rate was significantly higher in NSV (χ² = 4.14, P < 0.05). The positivity rates of the three autoantibodies differed significantly according to age of onset (P = 0.001, P = 0.02 and P < 0.001 for Tg Ab, ANA and TPO Ab positivity, respectively). The TPO Ab positivity rate also showed a sex difference (P < 0.001). The positivity rates for the three autoantibodies showed differences according to age of onset and sex. The rates of Tg Ab and ANA positivity showed no significant differences according to clinical type, but the TPO Ab positivity rate was significantly different between SV and NSV. It appears likely that an autoimmune mechanism contributes to the pathogenesis of SV. © 2015 British Association of Dermatologists.

[Evaluation of a Computer-Aided Microscope System and Its Anti-Nuclear Antibody Test Kit for Indirect Immunofluorescence Assay].

PubMed

Hayashi, Nobuhide; Saegusa, Jun; Uto, Kenichi; Oyabu, Chinami; Saito, Toshiharu; Sato, Itsuko; Kawano, Seiji; Kumagai, Shunichi

2016-02-01

Antinuclear antibody (ANA) testing is indispensable for diagnosing and understanding clinical conditions of autoimmune diseases. The indirect immunofluorescence assay (IFA) is the gold standard for ANA screening, and it can detect more than 100 different antibodies, such as anti-PCNA as well as anti-cytoplasmic antibodies. However, complicated procedures of conventional IFA and visual interpretation require highly skilled laboratory staff. This study evaluates the capability, characteristics, and applicability of the recently developed ANA detection system (EUROPattern Cosmic IFA System, EPA) using HEp20-10 cells and the automated pattern recognition microscope. Findings using EPA and conventional methods were compared in 282 sera obtained from connective tissue disease patients and 250 sera from healthy individuals. The concordance of the positivity rate, antibody titer (within +/- 1 tube difference), and the accurate recognition rate of ANA patterns between the automated EPA method and the microscopic judgement of the EPA image by eye was 98.9, 97.4, and 55.3%, respectively. The EPA method showed concordance of the positivity rate as high as 93.3% and concordance of the antibody titer as high as 94.0% (within +/- 1 titer) compared with the conventional method. Regarding the four typical patterns of ANA (homogeneous, speckled, nucleolar, and centromere), large differences between the EPA and conventional methods were not observed, and the rate of concordance between the final EPA result and the conventional method was from 94.1 to 100%. The positivity rate of ANA using the EPA and conventional methods showed marked agreement among the six connective tissue diseases (SLE, MCTD, SSc, PM/DM, and SS) and healthy individuals. Although the EPA system is not considered a complete system and laboratory staff should verify the results, it is a useful system for routine ANA analysis because it contributes to ANA standardization and an efficient workflow.

Strategic perspective: Nuclear issues in the New Zealand media

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fridriksson, L.N.

New Zealand's anti-nuclear policy drew international attention and threw the nation into a foreign policy crisis with the United States over the trilateral mutual security pact ANZUS. After more than a year of diminished intelligence and military cooperation, New Zealand was expelled from the alliance. This study involved a content analysis of coverage of these events and other nuclear issues in selected newspapers of New Zealand and the United States. Research points to the roles of the media as a critical one in the overall relations among countries. Through their frequent use of official government sources, the media tend tomore » uphold the government line or status quo with regard to foreign affairs. This study sought to identify the nuclear issues covered in the New Zealand and US media, the characteristics of that coverage, the sources of that coverage and how coverage varied during changing US-New Zealand relations. The official frame prevailed in coverage of nuclear issues. In the New Zealand and US newspapers under study, most sources of nuclear issue news were government officials. This research also found that most coverage of nuclear issues in the New Zealand media was related to some aspect of US interests, and that coverage of New Zealand's policy in the US media was covered most often when related to the United States. Nuclear issue coverage was most often not crisis-oriented in New Zealand and US newspapers, but coverage of all nuclear issues increased dramatically during the period of the ANZUS policy crisis. This study found a number of changes in nuclear issue coverage in the New Zealand media after the policy crisis was resolved. Among those changes were a tendency to focus less on economic and trade effects of the anti-nuclear policy, a tendency to focus more on ties with other South Pacific nations, use more sources from those countries, and a tendency to focus less on the moral and ethical position of the country.« less

Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

PubMed

Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Cytokine-associated neutrophil extracellular traps and antinuclear antibodies in Plasmodium falciparum infected children under six years of age

PubMed Central

Baker, Virginia S; Imade, Godwin E; Molta, Norman B; Tawde, Pallavi; Pam, Sunday D; Obadofin, Michael O; Sagay, Soloman A; Egah, Daniel Z; Iya, Daniel; Afolabi, Bangmboye B; Baker, Murray; Ford, Karen; Ford, Robert; Roux, Kenneth H; Keller, Thomas CS

2008-01-01

Background In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to double-stranded DNA along with the cytokine profiles found suggests autoimmune mechanisms that could produce pathogenesis in children, but immunoprotection in adults. Methods Peripheral blood smear slides and blood samples obtained from 21 Nigerian children under six years of age, presenting with uncomplicated malaria before and seven days after initiation of sulphadoxine-pyrimethamine (SP) treatment were analysed. The slides were stained with Giemsa and with DAPI. Levels of the pro-inflammatory cytokines IFN-γ, IL-2, TNF, CRP, and IL-6, select anti-inflammatory cytokines TGF-β and IL-10, and ANA were determined by immunoassay. Results The children exhibited circulating NETs with adherent parasites and erythrocytes, elevated ANA levels, a Th2 dominated cytokine profile, and left-shifted leukocyte differential counts. Nonspecific ANA levels were significant in 86% of the children pretreatment and in 100% of the children seven days after SP treatment, but in only 33% of age-matched control samples collected during the season of low parasite transmission. Levels of ANA specific for dsDNA were significant in 81% of the children both pre-treatment and post treatment. Conclusion The results of this investigation suggest that NET formation and ANA to dsDNA may induce pathology in falciparum-infected children, but activate a protective mechanism against falciparum malaria in adults. The significance of in vivo circulating chromatin in NETs and dsDNA ANA as a causative factor in the hyporesponsiveness of CpG oligonucleotide-based malaria vaccines is discussed. PMID:18312656

Myeloperoxidase Antineutrophil Cytoplasmic Antibody (MPO-ANCA) Associated Crescentic and Necrotizing Glomerulonephritis (GN) with Membranoproliferative GN Features.

PubMed

Koda, Ryo; Nagahori, Katsuhiro; Kitazawa, Atsushi; Imanishi, Yuji; Yoshino, Atsunori; Kawamoto, Shinya; Ueda, Yoshihiko; Takeda, Tetsuro

2016-01-01

A 77-year-old man presented with a fever, non-productive cough, and edema formation. A laboratory analysis showed an elevated creatinine level (2.5 mg/dL), a high titer of myeloperoxidase (MPO)-anti-neutrophil cytoplasmic antibody (ANCA) (99 U/mL), positive reaction for antinuclear antibody (×320), hematuria, and massive proteinuria (3.33 g/day). A renal biopsy revealed crescentic and necrotizing glomerulonephritis (GN) with membranoproliferative GN features [double contour appearance of the glomerular basement membrane, granular deposition of immunoglobulin (Ig) G, IgM, and C3 along the capillary wall, subendothelial and subepithelial deposits with mesangial interposition]. A potential relationship between MPO-ANCA associated GN and membranoproliferative GN is discussed.

ANA testing in the presence of acute and chronic infections.

PubMed

Litwin, Christine M; Binder, Steven R

2016-01-01

Autoantibody testing is performed to help diagnose patients who have clinical symptoms suggestive of possible autoimmune diseases. Antinuclear antibodies (ANA) are present in many systemic autoimmune conditions such as systemic lupus erythematosus (SLE). However, a positive ANA test may also be seen with non-autoimmune inflammatory diseases, including both acute and chronic infections. When the ANA test is used as an initial screen in patients with non-specific clinical symptoms, such as fever, joint pain, myalgias, fatigue, rash, or anemia, the likelihood of a positive result due to infection will increase, especially in children. This article identifies acute and chronic infectious diseases that are likely to produce a positive ANA result and summarizes recent literature addressing both the causes and consequences of these findings.

Shwachman-Diamond syndrome with autoimmune-like liver disease and enteropathy mimicking celiac disease.

PubMed

Veropalumbo, Claudio; Campanozzi, Angelo; De Gregorio, Fabiola; Correra, Antonio; Raia, Valeria; Vajro, Pietro

2015-02-01

Liver abnormalities that normalize during infancy as well an enteropathy are reported in Shwachman-Diamond syndrome (SDS). The pathogenesis of both conditions is unknown. We report two SDS cases with autoimmune-like (antismooth muscle and/or antinuclear antibody positivity) liver disease and antigliadin antibody positive inflammatory enteropathy. Hypertransaminasemia did not resolve after immunosuppressive therapy and/or a gluten-free diet. These transient autoimmune phenomena and gut-liver axis perturbations may have played a role in transient SDS hepatopathy and enteropathy. Our report may stimulate other studies to define the relationship between the SDS genetic defect and intestinal permeability as the pathogenic mechanism underlying SDS related liver and intestinal inflammation. Copyright © 2014. Published by Elsevier Masson SAS.

[Prevalence of non-thyroid autoantibodies in autoimmune dysthyroidies].

PubMed

Guerin, V; Prestat, F; Bene, M C; Faure, G; Hartemann, P; Leclere, J

1989-01-01

Organ- and non organ-specific autoantibodies can be detected in patients with AITD but large comparative studies have seldom been performed. This study evaluated the prevalence of anti-thyroid, -smooth muscle, -mitochondria, -parietal gastric cells, -salivary duct, -nuclear and -ds DNA autoantibodies assayed by indirect immunofluorescence in 224 patients with Graves' disease or Hashimoto's thyroiditis. Results evidenced a high prevalence of antinuclear antibodies, mostly of non homogenous fluorescence in Graves' (63.1%) and Hashimoto's patients (65.5%), as well as for antisalivary duct antibodies (55.2 and 75%). No positive anti-ds DNA were noticed. No correlation was found between antithyroid antibodies and the others. Different hypothesis could explain this observation which favours a general dysregulation of the autoimmune system.

[Cardiac tamponade disclosing systemic lupus erythematosus].

PubMed

Nour-Eddine, M; Bennis, A; Soulami, S; Chraibi, N

1996-02-01

Cardiac tamponade secondary to systemic lupus erythematosus is rare and has a very serious prognosis. The authors report a case of cardiac tamponade confirmed by echocardiography, which constituted the presenting sign of systemic lupus erythematosus in a 20-year-old patient, who required emergency pericardial aspiration. The diagnosis of systemic lupus erythematosus was established on the basis of the combination of pericardial involvement, non-erosive arthritis, leukopenia with lymphopenia, presence of LE cells and anti-native DNA antibodies and positive antinuclear antibody titre of 1/2560. The clinical course was favourable in response to 3 months of corticosteroid treatment. The possibility of SLE should be considered in any case of cardiac tamponade in a young patient in which the aetiology is not explained.

An elderly ‘kawara’ craftsman with acute kidney injury and haemoptysis: a case of silica-induced autoimmunity

PubMed Central

Matsui, Satoshi; Tsuji, Hiroko; Ono, Shinji

2011-01-01

A 62-year-old Japanese ‘kawara’ (ceramic roof tile) craftsman presented with acute kidney injury and haemoptysis. This case met the systemic lupus erythematosus and microscopic polyangiitis criteria, with high titres of myeloperoxidase–antineutrophil cytoplasmic antibody (570 EU). Results showed the presence of antinuclear antibody at a high titre (1:2560), but detection of rheumatoid factor, anti-dsDNA, anti-SSA and anti-SSB antibodies was not apparent. This serology was similar to drug-induced, silicon-induced or silica-induced autoimmunity. The patient had been exposed to silica for > 40 years. The environmental aetiology of autoimmune diseases should be considered in cases that show atypical epidemiology and serology. PMID:25984095

HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms.

PubMed

Tancharoen, Salunya; Gando, Satoshi; Binita, Shrestha; Nagasato, Tomoka; Kikuchi, Kiyoshi; Nawa, Yuko; Dararat, Pornpen; Yamamoto, Mika; Narkpinit, Somphong; Maruyama, Ikuro

2016-11-23

High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 ( Hmgb1 +/- ) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies. Palatal gingival explants were cultured with recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced glycation end products (RAGEs) for cell migration and PCNA expression analysis. Measurement of the wound area showed differences between Hmgb1 +/- and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas in Hmgb1 +/- mice weave-like pattern of low density collagen bundles were present. At three and seven days post-surgery, PCNA, NF-κB p50 and VEGF positive keratinocytes of WT mice were greater than that of Hmgb1 +/- mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell migration and PCNA expression in gingival cell cultures. The data suggest that HMGB1/RAGE axis has crucial roles in palatal wound healing.

Histocompatibility antigens in a population based silicosis series.

PubMed Central

Kreiss, K; Danilovs, J A; Newman, L S

1989-01-01

Individual susceptibility to silicosis is suggested by the lack of a uniform dose response relation and by the presence of immunological epiphenomena, such as increased antibody levels and associated diseases that reflect altered immune regulation. Human leucocyte antigens (HLA) are linked with immune response capability and might indicate a possible genetic susceptibility to silicosis. Forty nine silicotic subjects were identified from chest radiographs in a population based study in Leadville, Colorado. They were interviewed for symptoms and occupational history and gave a blood specimen for HLA-A, -B, -DR, and -DQ typing and for antinuclear antibody, immune complexes, immunoglobulins, and rheumatoid factor. Silicotic subjects had twice the prevalence of B44 (45%) of the reference population and had triple the prevalence of A29 (20%), both of which were statistically significant when corrected for the number of comparisons made. No perturbations in D-region antigen frequencies were detected. B44-positive subjects were older at diagnosis and had less dyspnoea than other subjects. A29-positive subjects were more likely to have abnormal levels of IgA and had higher levels of immune complexes. This study is the first to find significant HLA antigen excesses among a series of silicotic cases and extends earlier reported hypotheses that were based on groups of antigens of which B44 and A29 are components. PMID:2818968

Esophageal abnormalities in juvenile localized scleroderma: is it associated with other extracutaneous manifestations?

PubMed

Valões, Clarissa C M; Novak, Glaucia V; Brunelli, Juliana B; Kozu, Katia T; Toma, Ricardo K; Silva, Clovis A

To assess esophageal involvement (EI) in juvenile localized scleroderma (JLS) population and the possible association between this gastrointestinal manifestation and demographic data, clinical features, laboratory exams, treatments and outcomes. For a period of 30 years, 5881 patients with rheumatic diseases were followed in our Pediatric Rheumatology Division. EI was defined by the presence of symptoms (solid/liquid dysphagia, heartburn, esophageal regurgitation, nausea/vomiting and epigastralgia) and confirmed by at least one EI exam abnormality: barium contrast radiography, upper gastrointestinal endoscopy and 24-hour esophageal pH-monitoring. JLS was observed in 56/5881 patients (0.9%), mainly linear morphea subtype. EI was observed in 23/56(41%) of JLS patients. Eight(35%) of 23 EI patients with JLS were symptomatic and presented heartburn(5/8), solid and liquid dysphagia(3/8), nausea and epigastralgia(1/8). The frequency of any cumulative extracutaneous manifestations (calcinosis, arthritis/arthralgia, central nervous system, interstitial pneumonitis, mesangial nephritis and/or arrhythmia) was significantly higher in JLS patients with EI compared to those without this complication (56% vs. 24%, p=0.024). No differences were evidenced in demographic data, JLS subtypes and in each extracutaneous manifestation in both groups (p>0.05). The frequency of methotrexate use was significantly higher in JLS patients with EI compared to those without (52% vs. 12%, p=0.002). Autoantibody profile (antinuclear antibodies, anti-SCL-70, rheumatoid factor, anticentromere, anti-cardiolipin, anti-Ro/SSA and anti-La/SSB) was similar in both groups (p>0.05). Our study demonstrated that EI was frequently observed in JLS patients, mainly in asymptomatic patients with linear subtype. EI occurred in JLS patients with other extracutaneous manifestations and required methotrexate therapy. Copyright © 2016. Published by Elsevier Editora Ltda.

Autoimmune acute liver failure: proposed clinical and histological criteria.

PubMed

Stravitz, R Todd; Lefkowitch, Jay H; Fontana, Robert J; Gershwin, M Eric; Leung, Patrick S C; Sterling, Richard K; Manns, Michael P; Norman, Gary L; Lee, William M

2011-02-01

Identifying autoimmune hepatitis as the etiology of acute liver failure (ALF) is potentially important, because administering corticosteroids might avoid the need for liver transplantation. However, clinical and histological criteria of autoimmune ALF (AI-ALF) have not been defined. Liver sections (biopsies and explants) from a 72-patient subset of the ALF Study Group Registry with indeterminate ALF were reviewed by a pathologist blinded to all clinical data and were diagnosed with probable AI-ALF based on four features suggestive of an autoimmune pathogenesis: distinctive patterns of massive hepatic necrosis (present in 42% of sections), presence of lymphoid follicles (32%), a plasma cell-enriched inflammatory infiltrate (63%), and central perivenulitis (65%). Forty-two sections (58%) were considered probable for AI-ALF; this group demonstrated higher serum globulins (3.7 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P = 0.037) and a higher prevalence of antinuclear and/or anti-smooth muscle antibodies (73% versus 48%; P = 0.034) compared to those without histology suggestive of probable AI-ALF. Thirty patients concordant for autoantibodies and probable AI-ALF upon histological analysis were more likely to have the classical autoimmune hepatitis phenotype (female predominance [72% versus 48%; P < 0.05], higher globulins [3.9 ± 0.2 g/dL versus 3.0 ± 0.2 g/dL; P < 0.005], and higher incidence of chronic hepatitis in long-term follow-up [67% versus 17%, P = 0.019]) compared to the population without concordant AI-ALF histology and autoantibodies. Patients with indeterminate ALF often have features of autoimmune disease by histological analysis, serological testing, and clinical recurrence during follow-up. In contrast to classical autoimmune hepatitis, histological features of AI-ALF predominate in the centrilobular zone. Copyright © 2010 American Association for the Study of Liver Diseases.

Open literature review of threats including sabotage and theft of fissile material transport in Japan.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cochran, John Russell; Furaus, James Phillip; Marincel, Michelle K.

This report is a review of open literature concerning threats including sabotage and theft related to fissile material transport in Japan. It is intended to aid Japanese officials in the development of a design basis threat. This threat includes the external threats of the terrorist, criminal, and extremist, and the insider threats of the disgruntled employee, the employee forced into cooperation via coercion, the psychotic employee, and the criminal employee. Examination of the external terrorist threat considers Japanese demographics, known terrorist groups in Japan, and the international relations of Japan. Demographically, Japan has a relatively homogenous population, both ethnically andmore » religiously. Japan is a relatively peaceful nation, but its history illustrates that it is not immune to terrorism. It has a history of domestic terrorism and the open literature points to the Red Army, Aum Shinrikyo, Chukaku-Ha, and Seikijuku. Japan supports the United States in its war on terrorism and in Iraq, which may make Japan a target for both international and domestic terrorists. Crime appears to remain low in Japan; however sources note that the foreign crime rate is increasing as the number of foreign nationals in the country increases. Antinuclear groups' recent foci have been nuclear reprocessing technology, transportation of MOX fuel, and possible related nuclear proliferation issues. The insider threat is first defined by the threat of the disgruntled employee. This threat can be determined by studying the history of Japan's employment system, where Keiretsu have provided company stability and lifetime employment. Recent economic difficulties and an increase of corporate crime, due to sole reliability on the honor code, have begun to erode employee loyalty.« less

Autoantibodies in Autoimmune Hepatitis.

PubMed

Muratori, Luigi; Deleonardi, Gaia; Lalanne, Claudine; Barbato, Erica; Tovoli, Alessandra; Libra, Alessia; Lenzi, Marco; Cassani, Fabio; Muratori, Paolo

2015-01-01

The detection of diagnostic autoantibodies such as antinuclear antibodies (ANA), anti-smooth muscle antibodies (SMA), anti-liver/kidney microsomal type 1 (anti-LKM1), anti-liver cytosol type 1 (anti-LC1) and anti-soluble liver antigen (anti-SLA) is historically associated with the diagnosis of autoimmune hepatitis. When autoimmune hepatitis is suspected, the detection of one or any combination of diagnostic autoantibodies, by indirect immunofluorescence or immuno-enzymatic techniques with recombinant antigens, is a pivotal step to reach a diagnostic score of probable or definite autoimmune hepatitis. Diagnostic autoantibodies (ANA, SMA, anti-LKM1, anti-LC1, anti-SLA) are a cornerstone in the diagnosis of autoimmune hepatitis. Other ancillary autoantibodies, associated with peculiar clinical correlations, appear to be assay-dependent and institution-specific, and validation studies are needed. © 2015 S. Karger AG, Basel.

Auto-immune hepatitis following delivery.

PubMed

Saini, Vandana; Gupta, Mamta; Mishra, S K

2013-05-01

Auto-immune hepatitis first presenting in the early postpartum period is rare. Immunosuppressive effects of pregnancy result in delayed manifestation of auto-immune hepatitis, and in established cases, the spontaneous improvements are there. Auto-immune hepatitis should be considered in the differential diagnosis of liver dysfunction first presenting in the early postpartum period. A case of postpartum hepatitis of auto-immune aetiology is being presented here. It is disease of unknown aetiology, characterised by inflammation of liver (as evidenced by raised serum transaminases, presence of interface hepatitis on histological examination), hypergammaglobulinaemia (> 1.5 times normal), presence of auto-antibodies [(antinuclear antibodies (ANA)], smooth muscle antibody (SMA) and antibody to liver-kidney microsome type 1 (LKM1) in the absence of viral markers ie, hepatitis B (HBsAg) and C (AntiHCV) and excellent response to corticosteroid therapy.

[Cutaneous and mucosal manifestations associated with cocaine use].

PubMed

Imbernón-Moya, Adrián; Chico, Ricardo; Aguilar-Martínez, Antonio

2016-06-17

Complications due to cocaine are a public health problem. The typical cutaneous disease is leukocytoclastic vasculitis and/or thrombotic vasculopathy affecting mainly the ears. No intense systemic involvement is usually present, but there may be several cutaneous, mucosal and systemic manifestations. Other findings associated as arthralgia, neutropaenia or agranulocytosis, low titer positive antinuclear antibodies, antiphospholipid antibody positivity and neutrophil cytoplasmic antibodies against multiple antigens help the diagnosis. This disease requires a clinical suspicion with a clinical history, a complete physical examination and a broad differential diagnosis for an early and correct diagnosis. The course is usually self-limited. In most cases the only treatment is to discontinue the use of cocaine associated with symptomatic treatment, no proven benefit of systemic corticosteroids. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Norwegian scabies in a malnourished young adult: a case report.

PubMed

Subramaniam, Girija; Kaliaperumal, Karthikeyan; Duraipandian, Jeyakumari; Rengasamy, Gopal

2010-06-03

A 19-year-old male was admitted to the medical ward with complaints of fever and swelling of the ankle and wrist joints of about two weeks duration. The patient developed hyperkeratotic lesions of the skin over the hands, elbow and back about three weeks after admission. Antistreptolysin O, rheumatoid factor, and Widal tests as well as Chickungunya, brucella, HIV and antinuclear antibodies were negative. Culture of blood sample and pus aspirate from the ankle and chest yielded a pure growth of Staphylococcus epidermidis. Potassium hydroxide (KOH) mount of the scrapings from crusted skin lesions showed plenty of adult mites, eggs and faecal pellets of Sarcoptes scabiei. A diagnosis of crusted scabies with secondary bacterial infection was made and the patient was treated successfully with oral ivermectin, topical permethrin and vancomycin.

[A case of systemic lupus erythematosus discovered from left heart failure due to lupus induced mitral regurgitation].

PubMed

Ueno, K; Fujimoto, S; Fujimoto, T; Nakano, H; Nakajima, T; Yamano, S; Shiiki, H; Hashimoto, T; Imoto, K; Miyagawa, S; Dohi, K

1999-10-01

A 50-year-old female was admitted to a local hospital because of dyspnea, and diagnosed as having left heart failure secondary to mitral regurgitation. After the improvement of congestive heart failure, polyarthralgia, fever, and positive anti-nuclear antibody were pointed out. She was referred to our hospital for the further evaluation. Serological test showed anti-double stranded DNA antibodies, anti-SS-A antibodies, anti-beta 2-GPI antibodies and biological false positive for syphilis. The diagnosis of SLE has been made from the clinical signs and the serology. Therefore mitral valvular lesion of this patient was considered to be one of the symptoms of SLE. We reported a rare case in which left heart failure was a initial clinical manifestation of SLE.

A phase 2, randomised, placebo-controlled clinical trial of blisibimod, an inhibitor of B cell activating factor, in patients with moderate-to-severe systemic lupus erythematosus, the PEARL-SC study.

PubMed

Furie, R A; Leon, G; Thomas, M; Petri, M A; Chu, A D; Hislop, C; Martin, R S; Scheinberg, M A

2015-09-01

To evaluate the efficacy and safety of subcutaneous blisibimod, an inhibitor of B cell activating factor, in patients with systemic lupus erythematosus (SLE) in a dose-ranging Phase 2b clinical trial. 547 patients with SLE with anti-double stranded DNA or antinuclear antibodies and Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index (SELENA-SLEDAI) score ≥6 at baseline were randomised to receive placebo or blisibimod at one of 3 dose levels. The primary end point, measured at Week 24, was the SLE Responder Index-5 (SRI-5, meeting established SRI criteria but with ≥5 point improvement in SELENA-SLEDAI). Although SRI-5 response rates were not significantly improved in the pooled blisibimod groups compared with placebo, they were higher in subjects randomised to the highest dose of blisibimod (200 mg once-weekly (QW)) compared with pooled placebo, from Week 16 to Week 24, reaching statistical significance at Week 20 (p=0.02). SRI response rates compared with placebo were higher still in subjects who attained SELENA-SLEDAI improvements of ≥8, and in a subgroup of patients with severe disease (SELENA-SLEDAI ≥10 and receiving corticosteroids at baseline). In subjects with protein:creatine ratios of 1-6 at baseline, significant reductions in proteinuria were observed with blisibimod. Significant (p<0.01) changes in anti-double stranded DNA antibodies, complement C3 and C4, and reductions in B cells were observed with blisibimod.No imbalances in serious adverse events or infections (4/280 and 3/266), deaths (4/280 and 3/266) and malignancies (2/280 and 2/266) were reported for blisibimod compared with placebo. This study successfully identified a safe, effective and convenient dose, study population and end point for evaluation of blisibimod effect in Phase 3. NCT01162681. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Erionite induces production of autoantibodies and IL-17 in C57BL/6 mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zebedeo, Christian Nash; Davis, Chad; Peña, Cecelia

Background: Erionite has similar chemical and physical properties to amphibole asbestos, which induces autoantibodies in mice. Current exposures are occurring in North Dakota due to the use of erionite-contaminated gravel. While erionite is known to cause mesothelioma and other diseases associated with asbestos, there is little known about its effects on the immune system. Objectives: We performed this study to determine whether erionite evokes autoimmune reactions in mice. Methods: Bone marrow derived macrophages (BMDM) were used to measure toxicity induced by erionite. Cytokine production by BMDM and splenocytes of C57BL/6 mice was examined by bead arrays and ELISA following exposuremore » to erionite, amphiboles and chrysotile. Wild type C57BL/6 mice were exposed to saline, erionite, amphibole asbestos (Libby 6-Mix) or chrysotile through intratracheal instillations at equal mass (60 μg/mouse). Seven months after exposure, sera were examined for anti-nuclear antibodies (ANA) and IL-17. Immunohistochemistry was used to detect immune complex deposition in the kidneys. Results: Erionite and tremolite caused increased cytokine production belonging to the T{sub H}17 profile including IL-17, IL-6, TGF-β, and TNF-α. The frequency of ANA was increased in mice treated with erionite or amphibole compared to saline-treated mice. IL-17 and TNF-α were elevated in the sera of mice treated with erionite. The frequency of immune complex deposition in the kidneys increased from 33% in saline-treated mice to 90% with erionite. Conclusions: These data demonstrate that both erionite and amphibole asbestos induce autoimmune responses in mice, suggesting a potential for adverse effects in exposed communities. - Highlights: • Erionite, a fibrous mineral, is a current public health concern in the western USA. • Erionite exposure induces antinuclear autoantibodies in exposed mice. • Erionite induces a clear Th17 cytokine response in vitro and in vivo. • These responses were distinct from responses caused by asbestos. • These data in mice suggest that exposed humans may be at risk for autoimmunity.« less

Alterations in nuclear structure promote lupus autoimmunity in a mouse model

PubMed Central

Singh, Namrata; Johnstone, Duncan B.; Martin, Kayla A.; Tempera, Italo; Kaplan, Mariana J.

2016-01-01

ABSTRACT Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by the development of autoantibodies that recognize components of the cell nucleus. The vast majority of lupus research has focused on either the contributions of immune cell dysfunction or the genetics of the disease. Because granulocytes isolated from human SLE patients had alterations in neutrophil nuclear morphology that resembled the Pelger–Huet anomaly, and had prominent mis-splicing of mRNA encoding the nuclear membrane protein lamin B receptor (LBR), consistent with their Pelger–Huet-like nuclear morphology, we used a novel mouse model system to test the hypothesis that a disruption in the structure of the nucleus itself also contributes to the development of lupus autoimmunity. The lupus-prone mouse strain New Zealand White (NZW) was crossed with c57Bl/6 mice harboring a heterozygous autosomal dominant mutation in Lbr (B6.Lbric/+), and the (NZW×B6.Lbric)F1 offspring were evaluated for induction of lupus autoimmunity. Only female (NZW×B6.Lbric)F1 mice developed lupus autoimmunity, which included splenomegaly, kidney damage and autoantibodies. Kidney damage was accompanied by immune complex deposition, and perivascular and tubule infiltration of mononuclear cells. The titers of anti-chromatin antibodies exceeded those of aged female MRL-Faslpr mice, and were predominantly of the IgG2 subclasses. The anti-nuclear antibody staining profile of female (NZW×B6.Lbric)F1 sera was complex, and consisted of an anti-nuclear membrane reactivity that colocalized with the A-type lamina, in combination with a homogeneous pattern that was related to the recognition of histones with covalent modifications that are associated with gene activation. An anti-neutrophil IgM recognizing calreticulin, but not myeloperoxidase (MPO) or proteinase 3 (PR3), was also identified. Thus, alterations in nuclear structure contribute to lupus autoimmunity when expressed in the context of a lupus-prone genetic background, suggesting a mechanism for the development of lupus autoimmunity in genetically predisposed individuals that is induced by the disruption of nuclear architecture. PMID:27483354

Scleroderma and dentistry: Two case reports.

PubMed

Dixit, Shantanu; Kalkur, Chaithra; Sattur, Atul P; Bornstein, Michael M; Melton, Fred

2016-10-24

Scleroderma is a chronic connective tissue disorder with unknown etiology. It is characterized by excessive deposition of extracellular matrix in the connective tissues causing vascular disturbances which can result in tissue hypoxia. These changes are manifested as atrophy of the skin and/or mucosa, subcutaneous tissue, muscles, and internal organs. Such changes can be classified into two types, namely, morphea (localized) and diffuse (systemic). Morphea can manifest itself as hemifacial atrophy (Parry-Romberg syndrome) although this remains debatable. Hence, we present a case of morphea, associated with Parry-Romberg syndrome, and a second case with the classical signs of progressive systemic sclerosis. Case one: A 20-year-old man of Dravidian origin presented to our out-patient department with a complaint of facial asymmetry, difficulty in speech, and loss of taste sensation over the last 2 years. There was no history of facial trauma. After physical and radiological investigations, we found gross asymmetry of the left side of his face, a scar on his chin, tongue atrophy, relative microdontia, thinning of the ramus/body of his mandible, and sclerotic lesions on his trunk. Serological investigations were positive for antinuclear antibody for double-stranded deoxyribonucleic acid and mitochondria. A biopsy was suggestive of morphea. Hence, our final diagnosis was mixed morphea with Parry-Romberg syndrome. Case two: A 53-year-old woman of Dravidian origin presented to our out-patient department with a complaint of gradually decreasing mouth opening over the past 7 years. Her medical history was noncontributory. On clinical examination, we found her perioral, neck, and hand skin to be sclerotic. Also, her fingers exhibited bilateral telangiectasia. An oral examination revealed completely edentulous arches as well as xerostomia and candidiasis. Her serological reports were positive for antinuclear antibodies against centromere B, Scl-70, and Ro-52. A hand and wrist radiograph revealed acro-osteolysis of the middle finger on her right hand. Hence, our final diagnosis was progressive systemic sclerosis. Through this article, we have tried to emphasize the importance of a general examination when diagnosing rare systemic diseases such as scleroderma and the role of the general dentist when caring for such patients, even though they can be quite rare in general practice.

Autoantibody presentation in drug-induced liver injury and idiopathic autoimmune hepatitis: the influence of human leucocyte antigen alleles.

PubMed

Stephens, Camilla; Castiella, Agustin; Gomez-Moreno, Eva M; Otazua, Pedro; López-Nevot, Miguel-Ángel; Zapata, Eva; Ortega-Alonso, Aida; Ruiz-Cabello, Francisco; Medina-Cáliz, Inmaculada; Robles-Díaz, Mercedes; Soriano, German; Roman, Eva; Hallal, Hacibe; Moreno-Planas, José M; Prieto, Martin; Andrade, Raúl J; Lucena, M Isabel

2016-09-01

Positive autoantibody (AAB) titres are commonly encountered in autoimmune hepatitis (AIH) and in a proportion of drug-induced liver injury (DILI) patients. The underlying mechanism for selective AAB occurrence in DILI is unknown, but could be associated with variations in immune-associated genes. Hence, we aimed to analyse human leucocyte antigen (HLA) allele compositions in DILI with positive (+) and negative (-) AAB titres and in AIH patients. High-resolution genotyping of HLA class I (A, B, C) and II (DRB1, DQB1) loci was performed on 207 DILI and 50 idiopathic AIH patients and compared with 885 healthy Spanish controls. Compared with controls, HLA-B*08:01 [44 vs. 9.7%, P=3.7E-13/corrected P-value (Pc)=1.0E-11], C*07:01 (46 vs. 24%, P=6.4E-04/Pc=0.012), DRB1*03:01 (58 vs. 21.5%, P=5.0E-09/Pc=1.0E-07) and DQB1*02:01 (56 vs. 22%, P=6.8E-08/Pc=9.0E-07) were significantly more frequent in AIH patients. The HLA-A*01:01 frequency was increased in the same population, but did not reach significance after Bonferroni's correction (34 vs. 19%, P=0.02/Pc=0.37). Fifty-eight of 207 DILI patients presented positive titres for at least one AAB (predominantly antinuclear antibody 76% and antismooth muscle antibody 28%). There was a tendency towards higher representation of DRB1*14:01 and DQB1*05:03 in DILI AAB+ compared with DILI AAB- (13.8 vs. 4.0%, P=0.02/Pc=0.5; 13.8 vs. 4.7%, P=0.04/Pc=0.5). The presence of HLA alleles B*08:01, C*07:01, DRB1*03:01, DQB1*02:01 and possibly A*01:01 enhances the risk of AIH (type 1) in Spanish patients. These alleles form part of the ancestral haplotype 8.1. HLA-DRB1*14:01 and DQB1*05:03 could potentially increase the risk of positive AAB (particularly antinuclear antibody) in Spanish DILI patients.

Anti-nuclear autoantibodies in the general German population: prevalence and lack of association with selected cardiovascular and metabolic disorders-findings of a multicenter population-based study.

PubMed

Akmatov, Manas K; Röber, Nadja; Ahrens, Wolfgang; Flesch-Janys, Dieter; Fricke, Julia; Greiser, Halina; Günther, Kathrin; Kaaks, Rudolf; Kemmling, Yvonne; Krone, Bastian; Linseisen, Jakob; Meisinger, Christa; Moebus, Susanne; Obi, Nadia; Guzman, Carlos A; Conrad, Karsten; Pessler, Frank

2017-06-06

We determined the prevalence of anti-nuclear autoantibodies (ANAs) in the German adult population and examined the association between ANAs and cardiovascular and metabolic disorders. We used data and blood samples from the pretest phases of the German National Cohort, obtained from six of the 18 study centers (n = 1199). All centers applied standardized instruments including face-to-face interviews, anthropometric measurements and collection of blood samples. Self-reported histories of diabetes mellitus, heart attack and elevated blood cholesterol and/or lipids were recorded. Height, weight and blood pressure were measured. ANAs were detected using a semi-automated system (AKLIDES®; Medipan GmbH, Dahlewitz, Germany). A positive ANA was defined as a titer ≥ 1:80. ANA were classified as weakly (1:80 or 1:160), moderately (1:320 or 1:640) or strongly (≥1:1280) positive. Specific autoantibodies against nuclear antigens were detected with second-step assays according to the ANA staining pattern. Associations between the assessed disorders and ANA positivity and pattern were examined using sex and age-adjusted mixed-effects logistic regression models. Thirty-three percent (95% confidence interval; 31-36%) of the 1196 participants (measurements could not be obtained from three samples) were ANA positive (titer ≥ 1:80). The proportions of weakly, moderately and strongly positive ANA were 29%, 3.3% and 1.3%, respectively. ANA positivity was more common among women than men across all titers (χ 2 , p = 0.03). ANA positivity, even when stratified according to height of titer or immunofluorescent pattern, was not associated with diabetes, elevated blood cholesterol and/or lipids, obesity or hypertension. Second-step autoantibody assays were positive in 41 of the 83 samples (49%) tested, with anti-DFS70 (n = 13) and anti-dsDNA (n = 7) being most frequent. These subgroups were too small to test for associations with the disorders assessed. The prevalence of ANA positivity in the German general population was similar to values reported from other countries. Contrary to other studies, there was no association with selected self-reported and objectively measured cardiovascular and metabolic variables.

Differences between clinical and laboratory findings in patients with recent diagnosis of SLE according to the positivity of anti-dsDNA by the Crithidia luciliae method.

PubMed

Sarbu, M I; Salman-Monte, T C; Rubio Muñoz, P; Lisbona, M P; Almirall Bernabé, M; Carbonell, J

2015-10-01

Of all anti-dsDNA antibody detection methods, the Crithidia luciliae immunofluorescence test (CLIF) is considered to have the highest specificity for systemic lupus erythematosus (SLE). The objective of this report is to evaluate whether the presence of anti-dsDNA antibodies detected by the CLIF method is associated with a specific clinical phenotype in recently diagnosed SLE. This retrospective cross-sectional study included all patients with newly diagnosed SLE between 1990 and 2011 and followed up in our institution. Demographic, clinical and laboratory findings were assessed. Correlations between positivity of anti-dsDNA by the CLIF method, clinical and laboratory data were analyzed. A total of 104 patients were included in the analysis. Patients who were positive for anti-dsDNA by the CLIF method at the time of diagnosis had (statistically) significantly higher titers of anti-dsDNA by the ELISA method, antinuclear (ANA) and anticardiolipin antibodies, lymphopenia and complement consumption compared with the other two groups. Also they presented significantly more musculoskeletal symptoms at baseline. The presence of anti-dsDNA by the CLIF method in newly diagnosed SLE was associated with certain markers of increased disease activity. Its use could be a useful biomarker for a specific clinical phenotype suggestive of a more severe involvement at the time of the diagnosis. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Clinical evaluation of cobas core anti-dsDNA EIA quant.

PubMed

González, Concepción; Guevara, Paloma; García-Berrocal, Belén; Alejandro Navajo, José; Manuel González-Buitrago, José

2004-01-01

The measurement of antibodies to double-stranded DNA (anti-dsDNA) is a useful tool for the diagnosis and monitoring of patients with connective tissue diseases, particularly systemic lupus erythematosus (SLE). The aim of the present study was to compare a new enzyme-linked immunosorbent assay (ELISA) for the measurement of anti-dsDNA antibodies, which uses purified double-stranded plasmid DNA as the antigen (anti-dsDNA EIA Quant; Roche Diagnostics, Mannheim, Germany), with an established ELISA. The clinical usefulness of this new ELISA was also assessed. We measured anti-dsDNA antibodies in 398 serum samples that were divided into four groups: 1). routine samples sent to our laboratory for an antinuclear antibody (ANA) test (n=229), 2). samples from blood donors (n=74), 3). samples from patients with SLE (n=48), and 4) samples from patients with other autoimmune diseases (n=47). The methods used were the Cobas Core Anti-dsDNA EIA Quant (Roche Diagnostics, Mannheim, Germany) and the Anti-dsDNA test (Gull Diagnostics, Bois d'Arcy, France). We obtained a kappa index and Spearman correlation coefficient in the comparative study, and sensitivity, specificity, predictive values, and likelihood ratios in the clinical study. The results obtained show a good agreement between the two methods in both the qualitative results (kappa=0.91) and the quantitative data (r=0.854). The best accuracy, predictive values, likelihood ratios, and correlation with active disease were obtained with the Roche anti-dsDNA assay. Copyright 2004 Wiley-Liss, Inc.

Autoimmune hepatitis in children: what is different from adult AIH?

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoimmune hepatitis (AIH) is characterized by inflammatory liver histology, circulating non-organ-specific autoantibodies, and increased levels of immunoglobulin (Ig) G in the absence of a known etiology. Two types of childhood AIH are recognized according to seropositivity: smooth muscle antibody (SMA) and/or antinuclear antibody (ANA), which is AIH type 1; and antibodies to liver-kidney microsome type 1 (anti-LKM1), which is AIH type 2. There is a female predominance in both. Autoimmune hepatitis type 2 presents more acutely, at a younger age, and commonly with IgA deficiency; however, duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in the two groups. Immunosuppressive treatment with steroids and azathioprine, which should be instituted promptly to avoid progression to cirrhosis, induces remission in 80% of cases. Relapses are common, often due to nonadherence. Drugs effective in refractory cases include cyclosporine and mycophenolate mofetil. Long-term treatment is usually required, with only some 20% of AIH type 1 patients able to discontinue therapy successfully. In childhood, sclerosing cholangitis with strong autoimmune features, including interface hepatitis and serological features identical to AIH type 1, is as prevalent as AIH, but it affects boys and girls equally. The differential diagnosis relies on cholangiographic studies. In autoimmune sclerosing cholangitis, liver parenchymal damage responds satisfactorily to immunosuppressive treatment, whereas bile duct disease tends to progress. Copyright Thieme Medical Publishers.

Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1) in hepatitis C seropositive subjects on Crete, Greece.

PubMed

Drygiannakis, D; Lionis, C; Drygiannakis, I; Pappas, G; Kouroumalis, E

2001-01-01

Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV) has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C. One hundred and forty two patients (59 men and 83 women), who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women), which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL) technique on human epithelial cells from larynx cancer (HEp-2 cells), rat liver-kidney-stomach substrate (CT3) and Chrithidia Luciliae (CL). Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA), positive in 72 patients (50.7%). Anti-smooth muscle antibodies (ASMA) were detected in 33 patients (23.2%). Only one patient was positive for LKM1 autoantibodies. No autoantibodies were found in 38 patients (26.7%). Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%). Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM1 autoantibodies are exceptionally rare in these patients.

HMGB1 Promotes Intraoral Palatal Wound Healing through RAGE-Dependent Mechanisms

PubMed Central

Tancharoen, Salunya; Gando, Satoshi; Binita, Shrestha; Nagasato, Tomoka; Kikuchi, Kiyoshi; Nawa, Yuko; Dararat, Pornpen; Yamamoto, Mika; Narkpinit, Somphong; Maruyama, Ikuro

2016-01-01

High mobility group box 1 (HMGB1) is tightly connected to the process of tissue organization upon tissue injury. Here we show that HMGB1 controls epithelium and connective tissue regeneration both in vivo and in vitro during palatal wound healing. Heterozygous HMGB1 (Hmgb1+/−) mice and Wild-type (WT) mice were subjected to palatal injury. Maxillary tissues were stained with Mallory Azan or immunostained with anti-HMGB1, anti-proliferating cell nuclear antigen (PCNA), anti-nuclear factor-κB (NF-κB) p50 and anti-vascular endothelial growth factor (VEGF) antibodies. Palatal gingival explants were cultured with recombinant HMGB1 (rHMGB1) co-treated with siRNA targeting receptor for advanced glycation end products (RAGEs) for cell migration and PCNA expression analysis. Measurement of the wound area showed differences between Hmgb1+/− and WT mice on Day 3 after wounding. Mallory Azan staining showed densely packed of collagen fibers in WT mice, whereas in Hmgb1+/− mice weave-like pattern of low density collagen bundles were present. At three and seven days post-surgery, PCNA, NF-κB p50 and VEGF positive keratinocytes of WT mice were greater than that of Hmgb1+/− mice. Knockdown of RAGE prevents the effect of rHMGB1-induced cell migration and PCNA expression in gingival cell cultures. The data suggest that HMGB1/RAGE axis has crucial roles in palatal wound healing. PMID:27886093

Race, Income, and Disease Outcomes in Juvenile Dermatomyositis.

PubMed

Phillippi, Kathryn; Hoeltzel, Mark; Byun Robinson, Angela; Kim, Susan

2017-05-01

To determine the relationships among race, income, and disease outcomes in children with juvenile dermatomyositis (JDM). Data from 438 subjects with JDM enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were analyzed. Demographic data included age, sex, race, annual family income, and insurance status. Clinical outcomes included muscle strength, presence of rash, calcinosis, weakness, physical function, and quality of life measures. Disease outcomes were compared based on race and income. Minority subjects were significantly more likely to have low annual family income and significantly worse scores on measures of physical function, disease activity, and quality of life measures. Subjects with lower annual family income had worse scores on measures of physical function, disease activity, and quality of life scores, as well as weakness. Black subjects were more likely to have calcinosis. Despite these differences in outcome measures, there were no significant differences among the racial groups in time to diagnosis or duration of disease. Using calcinosis as a marker of disease morbidity, black race, annual family income <$50 000 per year, negative antinuclear antibody, and delay in diagnosis >12 months were associated with calcinosis. Minority race and lower family income are associated with worse morbidity and outcomes in subjects with JDM. Calcinosis was more common in black subjects. Further studies are needed to examine these associations in more detail, to support efforts to address health disparities in subjects with JDM and improve disease outcomes. Copyright © 2017 Elsevier Inc. All rights reserved.

Pathogenic mechanisms in systemic lupus erythematosus.

PubMed

Perl, Andras

2010-02-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease characterized by the dysfunction of T cells, B cells, and dendritic cells and by the production of antinuclear autoantibodies. This editorial provides a synopsis of newly discovered genetic factors and signaling pathways in lupus pathogenesis that are documented in 11 state-of-the-art reviews and original articles. Mitochondrial hyperpolarization underlies mitochondrial dysfunction, depletion of ATP, oxidative stress, abnormal activation, and death signal processing in lupus T cells. The mammalian target of rapamycin, which is a sensor of the mitochondrial transmembrane potential, has been successfully targeted for treatment of SLE with rapamycin or sirolimus in both patients and animal models. Inhibition of oxidative stress, nitric oxide production, expression of endogenous retroviral and repetitive elements such as HRES-1, the long interspersed nuclear elements 1, Trex1, interferon alpha (IFN-alpha), toll-like receptors 7 and 9 (TLR-7/9), high-mobility group B1 protein, extracellular signal-regulated kinase, DNA methyl transferase 1, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, actin cytoskeleton formation, the nuclear factor kappa B pathway, and activation of cytotoxic T cells showed efficacy in animal models of lupus. Although B cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, human studies are currently ongoing to establish the value of several target molecules for treatment of patients with lupus. Ongoing oxidative stress and inflammation lead to accelerated atherosclerosis that emerged as a significant cause of mortality in SLE.

Rheumatic Disease Autoantibodies in Autoimmune Liver Diseases.

PubMed

Utiyama, Shirley R R; Zenatti, Katiane B; Nóbrega, Heloisa A J; Soares, Juliana Z C; Skare, Thelma L; Matsubara, Caroline; Muzzilo, Dominique A; Nisihara, Renato M

2016-08-01

Autoimmune liver diseases (ALDs) are known to be associated with systemic autoimmune rheumatic diseases (SARDs) and their autoantibodies. We aimed to study the prevalence of SARDs and related autoantibodies, as well as their prognostic implications in a group of patients with ALDs. This was a cross-sectional study. Sixty patients with ALDs (38.3% with autoimmune hepatitis; 11.7% with primary biliary cirrhosis; 25% with primary sclerosing cholangitis and 25% with overlap syndrome) were studied for the presence of SARDs and their autoantibodies. There was autoimmune rheumatic disease in 20% of the studied sample. Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) were the commonest (11.6% and 5%, respectively). Antinuclear antibodies (ANAs) were present in 35% of the patients, followed by anti-Ro (20.0%); anti-nucleosome (18.3%); rheumatoid factor (10%) anti-CCP (8.3%); anti-RNP (8.3%); anti-ds-DNA (6.6%); anti-La (3.3%); anti-Sm (3.3%), anti-ribosomal P (3.3%). Anti-Ro (p = 0.0004), anti-La (p = 0.03), anti-RNP (p = 0.04) and anti-Sm (p = 0.03) were commonly found in patients with SARD, but not anti-DNA, anti-nucleosome and anti-ribosomal P. No differences were found in liver function tests regarding to the presence of autoantibodies. There was a high prevalence of SARD and their autoantibodies in ALD patients. Anti-Ro, anti-La, anti-RNP and anti-Sm positivity points to an association with systemic autoimmune rheumatic diseases. The presence of autoantibodies was not related to liver function tests.

Serum C-reactive protein concentrations in Nova Scotia Duck Tolling Retrievers with immune-mediated rheumatic disease.

PubMed

Bremer, Hanna Dorotea; Hillström, Anna; Kånåhols, Malin; Hagman, Ragnvi; Hansson-Hamlin, Helene

2017-04-17

Nova Scotia Duck Tolling Retrievers (NSDTRs) are a dog breed often affected by immune-mediated rheumatic disease (IMRD), a disorder characterised by chronic stiffness and joint pain. Most, but not all, dogs with IMRD, have antinuclear antibodies (ANA), which are also commonly present in the autoimmune disease systemic lupus erythematosus (SLE). The clinical and diagnostic findings of IMRD indicate that it is an SLE-related disorder. C-reactive protein (CRP), an acute phase protein, is a quantitative marker of inflammation for many diseases and is used for diagnosing and monitoring systemic inflammation in both humans and dogs. However, in human SLE, CRP concentrations are often elevated but correlate poorly with disease activity; they can be low in individual patients with active disease. The aim of the study was to investigate CRP in a group of NSDTRs with the SLE-related disorder IMRD. The hypothesis was that CRP concentrations would be increased in dogs with IMRD compared to healthy dogs, but that the increase would be mild. Serum CRP concentrations were measured in 18 IMRD-affected NSDTRs and 19 healthy control NSDTRs using two different canine-specific CRP assays. Dogs with IMRD and ANA had higher CRP concentrations than the control dogs, but the concentrations were below the clinical decision limit for systemic inflammation for most of the IMRD dogs. These results indicate that CRP concentrations were increased in dogs with IMRD and ANA, but the increase was mild, similar to what has been observed in human SLE.

Protein-losing enteropathy associated with refractory systemic lupus erythematosus with a good response to rituximab.

PubMed

Sansinanea, Pierina; Carrica, Sebastián Augusto; Marcos, Josefina; García, Mercedes Argentina

2016-01-01

A case is presented of a protein-losing enteropathy (PLE) as the initial manifestation of systemic lupus erythematosus (SLE) in a 17 year-old female patient, who presented with ascites, edema and hypoalbuminemia. The diagnosis of SLE was based on the presence of: malar rash, oral ulcers, thrombocytopenia, antinuclear antibodies, IgM anticardiolipin antibody, and lupus anticoagulant. Renal and liver diseases were ruled out. The PLE diagnosis was confirmed with fecal alpha 1-antitrypsin clearance. The PLE was refractory to different lines of immunosuppressive agents like glucocorticoids, cyclophosphamide, azathioprine, and cyclosporine, showing a satisfactory and sustained response with rituximab, allowing steroid sparing and long term remission. Copyright © 2014 Elsevier España, S.L.U. y Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Molecular diagnostic testing for primary biliary cholangitis.

PubMed

Gatselis, Nikolaos K; Dalekos, George N

2016-09-01

A reliable liver autoimmune serology for the diagnosis of primary biliary cholangitis (PBC) is of particular importance. Recognition of patients at early stages and prompt treatment initiation may alter the outcome, slow progression, delays liver failure, and improves survival. In this review, we summarize and discuss the published data obtained from literature searches from PubMed and The National Library of Medicine (USA) and our own experience on the current and potential molecular based approaches to the diagnosis of PBC. Expert commentary: Standardization of liver diagnostic serology and clinical governance are two major points as antimitochondrial antibodies are the diagnostic hallmark of the disease and PBC-specific antinuclear antibodies could assist in the diagnosis and estimation of prognosis. New biomarkers such as novel autoantibodies, genetic polymorphisms, metabolomic profiling, micro-RNA and epigenetics may assist to the understanding, diagnosis and management of the disease.

Health hazard evaluation report HETA 84-419-1697, USGS Laboratory, Doraville, Georgia. [Benzene, methylene chloride, hexane, and acetone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rondinelli, R.; Wilcox, T.; Roper, P.

1986-05-01

The U.S. Geological Survey National Water Quality Laboratory, Doraville, Georgia requested an evaluation of physical complaints reported by employees to determine possible work related causes. Laboratory workers, in general, complained of physical symptoms which were irritative (rash, sore throat, nose or sinus irritation), neurological (numbness, muscle weakness) and nonspecific (dizziness, headache, emotional swings, insomnia, muscle aching, fatigue). Reported exposure to solvents such as benzene, methylene chloride, hexane and acetone were positively related with light headedness or dizziness, numbness, unexplained muscle weakness and muscle aching. Air sampling did not reveal any remarkable exposure to chemical contaminants. The authors conclude that nomore » relationship could be established between chemical exposures and antinuclear antibody positivity. Exposure to chemicals measured by air sampling were below occupational health exposure limits.« less

The clinical impact of Anti-DFS70 antibodies in undifferentiated connective tissue disease: case reports and a review of the literature.

PubMed

Infantino, M; Meacci, F; Grossi, V; Manfredi, M; Li Gobbi, F; Sarzi-Puttini, P; Atzeni, F; Benucci, M

2017-02-01

Anti-nuclear antibody (ANA) positivity suggests CTD but can also lead to a diagnosis of UCTD when a patient does not fulfill the CTD diagnostic criteria. An anti-dense fine speckled (DFS) immunofluorescence (IIF) pattern can be observed when using an ANA test on HEp-2 cells and is due to the presence of antibodies to the nuclear DFS70 antigen that has rarely found in CTD. Serological testing for anti-DFS70 antibodies could therefore play a very interesting negative predictive role in stratifying patients on the basis of the evolution of UCTD to CTD. We described two patients ANA and anti-DFS70 positive in which the use of new method allowing the immunoadsorption of anti-DFS70 antibodies has permitted to exclude the incorrect diagnosis of CTD.

[Immunologic parameters in pericholangitis and primary sclerosing cholangitis with and without ulcerative colitis].

PubMed

Hopf, U; Riecken, E O; Zeitz, M; Eckhardt, R; Lobeck, H; Malchus, R; Möller, B

1983-10-07

Immunological parameters and histocompatibility antigens (HLA) were determined in seven patients with non-bacterial cholangitis. Four patients had pericholangitis and ulcerative colitis, three had primary sclerosing cholangitis, one of these with ulcerative colitis. All 7 patients had antinuclear antibodies; however, there were no antibodies against DNA, against mitochondria or liver membrane antigens. One patient had low-titre rheuma factors. Immunoglobulins G, A and M and complement components C3 and C4 were mostly in the normal range. HLA constellation was positive for B8 in 6 patients. These were male patients with disease manifestations between the 12th and 45th year of life. The results support the concept that pericholangitis and primary sclerosing cholangitis with or without ulcerative colitis are related hepatological disease entities with an immunological pathogenesis and an underlying genetical determination.

Lupus erythematosus (LE) cells in ascites: initial diagnosis of systemic lupus erythematosus by cytological examination: a case report.

PubMed

Chou, Kun-Ta; Lee, Yu-Chin; Chen, Chun-Wei; Shih, Jen-Fu; Tung, Su-Mei; Yang, Ya-Ting; Perng, Reury-Perng

2007-11-01

Systemic lupus erythematosus (SLE) is an autoimmune disease, involving multiple organs. Diverse manifestations may obscure the diagnosis and confuse our thinking process, especially when few clues are present at the beginning. Serositis is one of the various presentations, and the presence of lupus erythematosus (LE) cell in body fluid may be a hint for the final diagnosis of SLE. Herein, we present a young female patient diagnosed of SLE with initial presentation of lupus peritonitis. Finding of LE cell in ascites prompted us for immunologic survey. Diagnosis of SLE was confirmed with high titer of anti-nuclear antibody and antibody to double-stranded DNA. Cytologic examination of body fluid is mainly useful in detecting malignant cells, but high specificity of this marker aids in early diagnosis of SLE.

IgG4-negative autoimmune pancreatitis with sclerosing cholangitis and colitis: possible association with primary sclerosing cholangitis?

PubMed

Saeki, Keita; Hozawa, Shigenari; Miyata, Naoteru; Nishizawa, Toshihiro; Soma, Hiromitsu; Iwao, Yasushi; Kameyama, Kaori; Hibi, Toshifumi

2008-01-01

We report a case of autoimmune pancreatitis (AIP) with cholangiography and histopathology showing features characteristic of primary sclerosing cholangitis (PSC) and colitis. A 55-year-old previously-healthy man was diagnosed with anti-nuclear antibody (ANA)-positive AIP according to the finding of serum biochemistry, abdominal US (ultrasonography), CT (computed tomography) and ERCP (endoscopic retrograde cholangiopancreatography). However, bead-like strictures of intrahepatic bile ducts were also found and liver tissue showed onion skin-like periductal fibrosis but no anti-IgG4-positive cells. In addition, colon fiberscopy showed a pancolitis similar to ulcerative colitis indicating that, in this case, there may be an association with PSC. Here, we report a rare case of IgG4-negative AIP with sclerosing cholangitis and colitis with many clinical features that support an association with PSC.

Paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome): a report of two cases and review of the literature.

PubMed

Tunc, S Ercan; Arslan, Cagatay; Ayvacioglu, Naime Bayram; Sahin, Mehmet; Akkus, Selami; Yorgancigil, Huseyin

2004-07-01

We report two cases of paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) associated with prostatic adenocarcinoma. One of the patients was positive for Helicobacter pylori and the other had secondary bone metastases. In the latter, the clinical picture of RS3PE developed after surgical intervention for the primary lesion. On physical examination, while the hands and feet were swollen in the first patient, pitting edema was present only at the feet of the other. All joints of the affected hands and feet were painful. Serological tests including rheumatoid factor, antinuclear antibody, and human leukocyte antigen B27 were all negative. Response to low-dose corticosteroid treatment was delayed in the first patient, but the symptoms were relieved better in the second one.

Possible autoimmune hepatitis induced after chronic active Epstein-Barr virus infection.

PubMed

Wada, Yoshiko; Sato, Chikako; Tomita, Kyoko; Ishii-Aso, Rika; Haga, Hiroaki; Okumoto, Kazuo; Nishise, Yuko; Watanabe, Hisayoshi; Saito, Takafumi; Ueno, Yoshiyuki

2014-02-01

Chronic active Epstein-Barr virus infection (CAEBV) can be manifested in a variety of systemic conditions, including interstitial pneumonia, malignant lymphoma, and coronary aneurysm. Sometimes it may be associated with hepatic failure, although the mechanism underlying CAEBV-related hepatotoxicity remains unclear. We encountered a case of autoimmune hepatitis (AIH) associated with CAEBV. A 61-year-old male was referred to our hospital because of abnormal liver enzyme levels after initial diagnosis of CAEBV had been made by laboratory tests and liver biopsy. On admission, positivity for anti-nuclear antibody was evident, and examination of the liver biopsy specimen showed findings compatible with AIH. Steroid administration was initiated, and the liver function parameters subsequently improved. Although phenotypic changes in liver biopsy specimens are rare in this condition, the present case could provide clues to the possible pathogenesis of AIH.

Update on the Treatment of Uveitis in Patients with Juvenile Idiopathic Arthritis: A Review.

PubMed

Asproudis, Ioannis; Katsanos, Andreas; Kozeis, Nikolaos; Tantou, Alexandra; Konstas, Anastasios G

2017-12-01

Chronic uveitis is a common extra-articular manifestation of juvenile idiopathic arthritis. The classic clinical picture is one of chronic anterior uveitis, which usually remains asymptomatic until ocular complications arise. The risk of uveitis is increased in girls with an early onset of oligoarthritis and positive antinuclear antibodies. Even though the inflammation in patients with juvenile idiopathic arthritis is initially limited in the anterior part of the eye, chronic active inflammation may eventually cause significant damage to the posterior pole. Complications may include band keratopathy, cataract, secondary glaucoma, posterior synechiae, cystoid macular edema, and hypotony. The cooperation of ophthalmologists with rheumatologists may help define the best treatment plan. The ophthalmic therapeutic regimen includes topical corticosteroids and mydriatics, while in severe cases immunosuppressive and biological agents are introduced. Surgical management of complications might be needed.

Updates on the risk markers and outcomes of severe juvenile idiopathic arthritis-associated uveitis

PubMed Central

Angeles-Han, Sheila T; Yeh, Steven; Vogler, Larry B

2013-01-01

Uveitis is the most common extra-articular manifestation of juvenile idiopathic arthritis, which is the most common systemic cause of uveitis in children. Known risk factors for uveitis include antinuclear antibody seropositivity, young age of arthritis onset, specific juvenile idiopathic arthritis subtype and short duration of disease. Risk markers for severe ocular disease include gender, age and complications at initial visit. Due to the risk for vision-compromising sequelae such as cataracts, band keratopathy, glaucoma, vision loss and blindness, an understanding of the risk factors for uveitis development and severe ocular disease is crucial to help prevent serious visual disability and complications. This paper reviews the pathogenesis of uveitis, known risk factors for uveitis development and severe visual outcome, and addresses the need for additional biomarkers of uveitis risk, prognosis and remission. PMID:24187594

Hemophagocytic syndrome as one of the main primary manifestations in acute systemic lupus erythematosus--case report and literature review.

PubMed

Carvalheiras, G; Anjo, D; Mendonça, T; Vasconcelos, C; Farinha, F

2010-05-01

Hemophagocytic syndrome is an unusual but fatal disorder characterized by pancytopenia and activation of macrophages. We describe one case of acute systemic lupus erythematosus with an unusual presentation of hemophagocytic syndrome not related to infection. The patient presented with pancytopenia related to increasing hemophagocytic activity of histiocytes in the bone marrow. Concomitant class IV World Health Organization lupus nephritis, serositis, high titer of antinuclear factor and positive test for anti-DNA antibody fitted the diagnostic criteria of systemic lupus erythematosus. She also presented with alveolar hemorrhage and lupus myocarditis. She underwent immunosuppressive therapy with recovery from the hemophagocytic syndrome. Therefore, diagnosis of acute lupus hemophagocytic syndrome was made. The clinical presentation, laboratory diagnosis, and management of the patient are discussed and the literature was reviewed and presented, with emphasis on a possible distinct lupus subset, which includes a more aggressive systemic disease with heart involvement.

The universe of ANA testing: a case for point-of-care ANA testing.

PubMed

Konstantinov, Konstantin N; Rubin, Robert L

2017-12-01

Testing for total antinuclear antibodies (ANA) is a critical tool for diagnosis and management of autoimmune diseases at both the primary care and subspecialty settings. Repurposing of ANA from a test for lupus to a test for any autoimmune condition has driven the increase in ANA requests. Changes in ANA referral patterns include early or subclinical autoimmune disease detection in patients with low pre-test probability and use of negative ANA results to rule out underlying autoimmune disease. A positive result can lead to further diagnostic considerations. Currently, ANA tests are performed in centralized laboratories; an alternative would be ANA testing at the clinical point-of-care (POC). By virtue of its near real-time data collection capability, low cost, and ease of use, we believe the POC ANA has the potential to enable a new paradigm shift in autoimmune serology testing.

Autoimmune hepatitis in a teenage boy: 'overlap' or 'outlier' syndrome--dilemma for internists.

PubMed

Talukdar, Arunansu; Khanra, Dibbendhu; Mukherjee, Kabita; Saha, Manjari

2013-02-08

An 18-year-old boy presented with upper gastrointestinal bleeding and jaundice. Investigations revealed coarse hepatomegaly, splenomegaly and advanced oesophageal varices. Blood reports showed marked rise of alkaline phosphatase and more than twofold rise of transaminases and IgG. Liver histology was suggestive of piecemeal necrosis, interphase hepatitis and bile duct proliferation. Antinuclear antibody was positive in high titre along with positive antismooth muscle antibody and antimitochondrial antibody. The patient was positive for human leukocyte antigen DR3 type. Although an 'overlap' syndrome exists between autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC), a cholestatic variant of AIH, a rare 'outlier' syndrome could not be excluded in our case. Moreover, 'the chicken or the egg', AIH or PBC, the dilemma for the internists continued. The patient was put on steroid and ursodeoxycholic acid with unsatisfactory response. The existing international criteria for diagnosis of AIH are not generous enough to accommodate its variant forms.

Useful biomarkers for assessment of hepatitis C virus infection-associated autoimmune disorders

PubMed Central

Yang, Deng-Ho; Ho, Ling-Jun; Lai, Jenn-Haung

2014-01-01

During the course of chronic hepatitis C virus (HCV) infection, various extrahepatic manifestations of autoimmune disorders may occur, including arthralgia/arthritis, sicca complex, purpura, cutaneous ulcer, and thyroid dysfunction. In addition, the prevalence of circulating autoantibodies is high among patients with HCV infection. Commonly detected autoantibodies in HCV-infected patients include rheumatoid factor, antinuclear antibody, anti-SSA/anti-SSB antibody, cryoglobulin, antineutrophil cytoplasmic antibody, anti-smooth muscle antibody, anti-liver and anti-thyroid autoantibodies. These autoantibodies may be associated with underlying autoimmune disorders or liver inflammation in HCV infection. A possible reason for antibody production is overactivation and proliferation of B lymphocytes, via the interaction with the surface protein of HCV. Because immunotherapy can cause HCV flare-up or liver damage, overdiagnosis of HCV-related autoimmune symptoms as primary autoimmune disorders should be avoided. This review describes biomarkers that are useful in clinically evaluating autoimmune manifestations and disorders associated with HCV infection. PMID:24659887

First Trimester Hemolysis, Elevated Liver Enzymes, Low Platelets Syndrome in a Surrogate Pregnancy.

PubMed

Myer, Emily; Hill, James

2015-10-01

Background The occurrence of hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome before 20 weeks of gestation is rare. HELLP is a possible but rare syndrome in gestational surrogate pregnancies for surrogates with risk factors for development of preeclampsia. Case A 32-year-old patient with chronic hypertension and positive antinuclear antibody presented for prenatal care at 13 weeks and 1 day. She was a surrogate for the embryo of a 43-year-old couple. By 15 weeks she developed uncontrolled hypertension requiring hospitalization. She was expectantly managed until her condition deteriorated. At 16 weeks and 1 day she developed hemolysis, elevated liver enzymes, thrombocytopenia, and fetal demise. Conclusions HELLP syndrome is rare and carries a significant morbidity and mortality for the mother and fetus. Clinicians should encourage the surrogate to share her medical history with the embryo donor for appropriate counseling on pregnancy risks.

[Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

PubMed

Kotyla, Przemysław; Kucharz, Eugeniusz J

2012-01-01

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

Is Identification of Lupus Erythematosus Cells Still Useful? A Case Report.

PubMed

Xu, Min; MacNeal, Lucinda A; Wittman, Brenda J; Rutledge, Joe C

A 13-year-old girl presented with significant weight loss, depression, anemia, and neutropenia. The preliminary diagnosis was anorexia nervosa combined with depression. Due to peripheral cytopenia, a bone marrow biopsy was performed to rule out leukemia. Lupus erythematosus (LE) cells were found in the bone marrow aspirate, which prompted autoantibody testing, although clinically it was not suspected the patient had systemic lupus erythematosus (SLE). Further testing demonstrated very high levels of antinuclear antibodies (ANA) (>12 U) and anti-double strand DNA (dsNDA) (>1000 IU/mL), which confirmed the diagnosis of SLE. The patient was treated with steroids for SLE, and symptoms improved quickly. In conclusion, although the identification of LE cells as one of the diagnostic criteria for SLE has been obsolete, careful examination of bone marrow to identify LE cells is still very important in the diagnosis of unsuspected SLE.

Recurrent parotitis as a presentation of primary pediatric Sjögren syndrome.

PubMed

Baszis, Kevin; Toib, Dana; Cooper, Megan; French, Anthony; White, Andrew

2012-01-01

Parotitis is a common condition seen in the pediatric population, usually as an isolated occurrence associated with viral or bacterial infection. The differential diagnosis expands when recurrent parotitis is encountered. One etiology is primary pediatric Sjögren syndrome (SS), an autoimmune condition typically associated with dryness of the eyes and mouth in adults. Pediatric patients often present with isolated recurrent bilateral parotitis, however, and we describe 4 such cases in children aged 9 to 17 years at presentation. Despite lack of ocular complaints, 3 of these patients had ocular findings on ophthalmologic exam. Our patients also exhibited classic laboratory abnormalities, including positive antinuclear antibody, SS A, and SS B antibodies; presence of rheumatoid factor; and hypergammaglobulinemia. Consideration of SS in the child with recurrent parotitis is important for timely and appropriate referral and treatment. We review the differential diagnosis of parotitis in children as well as the salient features of pediatric SS.

Thrombo-ischaemic pinnal necrosis associated with fenbendazole treatment in a dog.

PubMed

Nuttall, T J; Burrow, R; Fraser, I; Kipar, A

2005-05-01

An 11-week-old, female West Highland white terrier was presented with necrosis of the distal third of both pinnae. Haematology, biochemistry and urinalysis, Coombs test, antinuclear antibody and cold autoagglutinin antibody tests were normal. A drug reaction to fenbendazole was diagnosed. The necrotic ear tips were surgically removed. Histopathology revealed extensive coagulative necrosis of the epidermis and superficial to mid-dermis, a moderate interstitial neutrophilic infiltrate and complete thrombotic occlusion and necrosis of blood vessels. There was also endothelial cell activation and proliferation with endothelial cell cushions protruding into the vascular lumen. Immunohistochemistry for factor VIII-related antigen confirmed endothelial cell involvement. This case represents an unusual, drug-induced, thrombo-ischaemic necrosis of the pinnae. It is also, to the authors' knowledge, the first report of fenbendazole sensitivity in a dog. The histopathology is similar to previous cases of proliferative thrombovascular pinnal necrosis, suggesting that drug reactions should be considered in this condition.

[Gastric neuroendocrine tumors in a woman with systemic lupus erythematosus].

PubMed

Döcker, D; Marx, U; Braun, B

2010-09-01

A 56-year-old woman presented with pronounced petechia. She complained about recurrent fever and night sweat for two weeks, having felt unwell during the past years. Laboratory examinations showed thrombocytopenia, leukopenia and considerably elevated liver enzymes. Antinuclear antibodies and antibodies against double-stranded DNA were positive. Sonography showed a slightly enlarged liver with multiple surrounding lymph nodes, splenomegaly and chronic-atrophic thyroiditis. Gastroscopy revealed several polypes which were immunohistochemically classified as neuroendocrine tumors (NET). Systemic lupus erythematosus (SLE) with involvement of several organs was diagnosed and high doses of steroids were given. The steroid was then gradually reduced and changed to azathioprine. The NET were removed endoscopically. Neuroendocrine tumors are rare and localised to the stomach in only 2 - 4 %. Only three cases of gastric NET in the context of SLE with autoimmune gastritis have been reported so far in the literature. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Ethics of energy production and use: debate within the National Council of Churches

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harnik, P.

1979-02-01

An Energy Policy Statement emanating from a panel for the National Council of Churches (NCC) in the United States was presented in May 1978 to the governing board of the NCC. The proposed Energy Policy Statement is composed of four sections: Opinions and Perspectives, Theological Dimensions of the Energy Situation, Ecological Justice and Human choice, and A Challenge to the Churches. Controversy concerning the proposed plan was great. The controversy on nuclear energy is specifically described. While the NCC was anti-nuclear, the World Council of Churches was tilting toward nuclear power. The NCC focused on ethics of energy and themore » WCC is not focusing on ethics; its nuclear statement does not constitute policy; and another WCC committee is aggressively promoting conservation and appropriate technology. The lessons drawn from the NCC debate are summarized. (MCW)« less

The Real Culprit in Systemic Lupus Erythematosus: Abnormal Epigenetic Regulation

PubMed Central

Wu, Haijing; Zhao, Ming; Chang, Christopher; Lu, Qianjin

2015-01-01

Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple organs and the presence of anti-nuclear antibodies. The pathogenesis of SLE has been intensively studied but remains far from clear. B and T lymphocyte abnormalities, dysregulation of apoptosis, defects in the clearance of apoptotic materials, and various genetic and epigenetic factors are attributed to the development of SLE. The latest research findings point to the association between abnormal epigenetic regulation and SLE, which has attracted considerable interest worldwide. It is the purpose of this review to present and discuss the relationship between aberrant epigenetic regulation and SLE, including DNA methylation, histone modifications and microRNAs in patients with SLE, the possible mechanisms of immune dysfunction caused by epigenetic changes, and to better understand the roles of aberrant epigenetic regulation in the initiation and development of SLE and to provide an insight into the related therapeutic options in SLE. PMID:25988383

Parvovirus B19 induced lupus-like syndrome with nephritis.

PubMed

Georges, Elodie; Rihova, Zuzana; Cmejla, Radek; Decleire, Pierre-Yves; Langen, Corinne

2016-12-01

We report a case of a 65-year-old man who developed an acute illness with fever, arthralgia and nephritic syndrome. Antinuclear antibodies were slightly positive and complement levels were low. Renal biopsy showed exudative diffuse proliferative endocapillary glomerulonephritis with diffuse immunoglobulin (IgG, IgA, IgM) and complement deposition (C3d, C4d, C1q) on immunofluorescence. The patient was first treated with corticosteroids and mycophenolate mofetil for suspected lupus with WHO class IV glomerulonephritis. The diagnosis was questioned and a diagnosis of parvovirus B19-associated nephritis was made based on elevation of serum IgM antibodies for parvovirus B19 and detection of parvovirus B19 DNA on renal biopsy. The immunosuppressive treatment was stopped and progressive spontaneous regression of clinical and laboratory abnormalities was observed. We conclude that human parvovirus B19 infection should be considered as a cause of lupus-like symptomatology and acute glomerulonephritis.

Immunologic findings, thrombocytopenia and disease activity in lupus nephritis.

PubMed Central

Clark, W. F.; Linton, A. L.; Cordy, P. E.; Keown, P. E.; Lohmann, R. C.; Lindsay, R. M.

1978-01-01

Twenty patients with nephritis due to systemic lupus erythematosus were followed up for a mean of 34 months after renal biopsy with serial determinations of total serum complement and C3 and C4 concentrations, binding of deoxyribonucleic acid (DNA), antinuclear antibody pattern and platelet count. There were 25 episodes of nonhematologic observed disease activity in 16 of the 20 patients; elevated DNA binding and thrombocytopenia correlated well with these episodes. The mean platelet count during episodes of observed disease activity was 96 +/- 42 X 10(9)/L, which was significantly different from the mean count of 248 +/- 90 X 10(9)/L during disease quiescence. The proportion of false-positive results with the immunologic tests varied from 25% to 67% and with platelet counts it was 11%. It is suggested that thrombocytopenia may be a simple and accurate index of disease activity in lupus nephritis. PMID:350367

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution.

PubMed

Dilia, Giuggioli; Michele, Colaci; Emanuele, Cocchiara; Amelia, Spinella; Federica, Lumetti; Clodoveo, Ferri

2018-01-01

Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0-156) months. LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset.

Minocycline-Induced Drug Hypersensitivity Syndrome Followed by Multiple Autoimmune Sequelae

PubMed Central

Brown, Rebecca J.; Rother, Kristina I.; Artman, Henry; Mercurio, Mary Gail; Wang, Roger; Looney, R. John; Cowen, Edward W.

2010-01-01

Background Drug hypersensitivity syndrome (DHS) is a severe, multisystem adverse drug reaction that may occur following the use of numerous medications, including anticonvulsants, sulfonamides, and minocycline hydrochloride. Long-term autoimmune sequelae of DHS have been reported, including hypothyroidism. Observations A 15-year-old female adolescent developed DHS 4 weeks after starting minocycline therapy for acne vulgaris. Seven weeks later she developed autoimmune hyperthyroidism (Graves disease), and 7 months after discontinuing minocycline therapy she developed autoimmune type 1 diabetes mellitus. In addition, she developed elevated titers of several markers of systemic autoimmune disease, including antinuclear, anti-Sjögren syndrome A, and anti-Smith antibodies. Conclusions Minocycline-associated DHS may be associated with multiple autoimmune sequelae, including thyroid disease, type 1 diabetes mellitus, and elevated markers of systemic autoimmunity. Long-term follow-up is needed in patients with DHS to determine the natural history of DHS-associated sequelae. PMID:19153345

False-positive cerebrospinal fluid cryptococcus antigen in Libman-Sacks endocarditis.

PubMed

Isseh, Iyad N; Bourgi, Kassem; Nakhle, Asaad; Ali, Mahmoud; Zervos, Marcus J

2016-12-01

Cryptococcus meningoencephalitis is a serious opportunistic infection associated with high morbidity and mortality in immunocompromised hosts, particularly patients with advanced AIDS disease. The diagnosis is established through cerebrospinal fluid (CSF) cryptococcus antigen detection and cultures. Cryptococcus antigen testing is usually the initial test of choice due its high sensitivity and specificity along with the quick availability of the results. We hereby report a case of a false-positive CSF cryptococcus antigen assay in a patient with systemic lupus erythematosus presenting with acute confusion. While initial CSF evaluation revealed a positive cryptococcus antigen assay, the patient's symptoms were inconsistent with cryptococcus meningoencephalitis. A repeat CSF evaluation, done 3 days later, revealed a negative CSF cryptococcus antigen assay. Given the patient's active lupus disease and the elevated antinuclear antibody titers, we believe that the initial positive result was a false positive caused by interference from autoantibodies.

An erythrodermic variant of pemphigus foliaceus with puzzling histologic and immunopathologic features.

PubMed

Peterson, Jennifer D; Worobec, Sophie M; Chan, Lawrence S

2007-01-01

Pemphigus foliaceus is an autoimmune blistering disorder that affects the skin owing to autoantibodies against desmoglein 1. We employed clinical, histologic, immunopathologic, and serum laboratory studies to investigate a case of an erythrodermic variant of pemphigus foliaceus in an elderly man following treatment with bisoprolol-hydrochlorothiazide. Early histopathology revealed psoriasiform dermatitis, but later biopsies showed subcorneal and granular layer separation with neutrophilic infiltrate. Direct immunofluorescence showed intercellular deposits of immunoglobulin G throughout the epidermis, granular staining of C3 along the basement membrane zone, and fibrin and C3 deposition around the blood vessels. Indirect immunofluorescence on monkey esophagus showed a titer of greater than 1:1,280. Indirect immunofluorescence on rat bladder, antinuclear antibody, lupus panel, and kidney function panel were all negative. There are no reports in the literature of pemphigus foliaceus being induced by bisoprolol, but reports exist of propanolol resulting in drug-induced pemphigus foliaceus.

Malaria, a difficult diagnosis in a febrile patient with sub-microscopic parasitaemia and polyclonal lymphocyte activation outside the endemic region, in Brazil

PubMed Central

2013-01-01

A case of autochthonous Plasmodium vivax malaria with sub-microscopic parasitaemia and polyclonal B-cell activation (PBA) (as reflected by positive IgM and IgG serology for toxoplasmosis, cytomegalovirus, and antinuclear and rheumatoid factors) was diagnosed by polymerase chain reaction (PCR) after consecutive negative rapid diagnostic test results and blood films. The patient, a 44-year-old man from Rio de Janeiro state, Brazil, had visited the Atlantic Forest, a tourist, non-malaria-endemic area where no autochthonous cases of ’bromeliad malaria‘ has ever been described. The characteristic pattern of fever, associated with PBA, was the clue to malaria diagnosis, despite consecutive negative thick blood smears. The study highlights a need for changes in clinical and laboratory diagnostic approaches, namely the incorporation of PCR as part of the current routine malaria diagnostic methods in non-endemic areas. PMID:24200365

Pro-Nuclear Environmentalism: Should We Learn to Stop Worrying and Love Nuclear Energy?

PubMed

van Munster, Rens; Sylvest, Casper

2015-10-01

In light of repeated failures to reach political agreement on effective policies to combat climate change, pro-nuclear environmentalists have set out to reverse the traditionally anti-nuclear inclinations of environmentalists. This essay examines the ideological commitments and assumptions of pro-nuclear environmentalism by performing a critical, historical analysis of the nuclear-environment nexus through the prism of documentary film. We focus on the work and career of documentary filmmaker Rob Stone, whose most recent production, Pandora's Promise (PP) (2013), has emerged as a central statement of this creed. PP actively forges a new political imaginary that replaces the apocalyptic image of nuclear fallout with that of catastrophic climate change. In terms of its rhetorical and visual strategies, however, PP also reveals that pro-nuclear environmentalist arguments have a long lineage. A close study of such continuities reveals a number of political implications that call for reflection as well as caution.

The (de)politicisation of nuclear power: The Finnish discussion after Fukushima.

PubMed

Ylönen, Marja; Litmanen, Tapio; Kojo, Matti; Lindell, Pirita

2017-04-01

When the Fukushima accident occurred in March 2011, Finland was at the height of a nuclear renaissance, with the Government's decision-in-principle in 2010 to allow construction of two new nuclear reactors. This article examines the nuclear power debate in Finland after Fukushima. We deploy the concepts of (de)politicisation and hyperpoliticisation in the analysis of articles in the country's main newspaper. Our analysis indicates that Finnish nuclear exceptionalism manifested in the safety-related depoliticising and the nation's prosperity-related hyperpoliticisation arguments of the pro-nuclear camp. The anti-nuclear camp used politicisation strategies, such as economic arguments, to show the unprofitability of nuclear power. The Fukushima accident had a clear effect on Finnish nuclear policy: the government programme of 2011 excluded the nuclear new build. However, in 2014 the majority of Parliament again supported nuclear power. Hence, the period after Fukushima until 2014 could be described as continued but undermined loyalty to nuclear power.

Acquired enophthalmos with systemic lupus erythematosus.

PubMed

Park, K R; Seo, M R; Ryu, H J; Chi, M J; Baek, H J; Choi, H J

2016-01-01

Ocular involvement sometimes occurs with systemic lupus erythematosus (SLE) but enophthalmos with SLE is rare. We report a case of enophthalmos with SLE. A 25-year-old male was admitted for two weeks of fever, sore throat, arthralgia, chest pain and right arm weakness with pain. We diagnosed him with SLE with malar rash, arthritis, pleural effusion, proteinuria, leukopenia, positive antinuclear antibody, anti-dsDNA, and lupus anticoagulant. The patient was prescribed high-dose prednisolone and hydroxychloroquine 400 mg. One week after discharge, he complained about a sensation of a sunken right eye. CT showed right enophthalmos, a post-inflammatory change and chronic inflammation. Proteinuria increased to 3.8 g/day after the patient stopped taking prednisolone. Cyclophosphamide therapy was administered for three months without improvement. We decided to restart prednisolone and change cyclophosphamide to mycophenolate mofetil. Proteinuria decreased but enophthalmos remains as of this reporting. © The Author(s) 2015.

Problems in paradise: the case of Tahiti.

PubMed

Danielson, M T

1993-01-01

Tahiti, situated in the Society Islands of the South Pacific among the 130 islands in the five archipelagos of French Polynesia, has very few indigenous populations. Population growth has been rapid under the conditions of military development and increasing immigration. When nuclear testing was approved in 1966, 18,000 troops arrived as did foreign migrants seeking work. Per capita income was high for the Pacific island countries, but distribution was very uneven. The transfers of administrative systems and law resulted in the loss of lands for some, who could not adjust to a foreign system. Today urban youth are confronted with high unemployment, malnutrition, disease, and overcrowding. The once beautiful lagoons have been contaminated with sewage and pesticides from soil erosion, caused in part by the careless construction along coastal areas. The most serious health problem is irradiation caused cancers: leukemia, thyroid infection, and brain tumors. There are also high levels of miscarriages. Lagoon fish have become contaminated by the disruptions to their habitat from detonation in two atolls. On the Mangareva Islands, all 600 residents died from ciguatera fish poisoning. Anti-nuclear groups have had very little impact. Polynesian women have suffered from these conditions and from the view that women are unclean and inferior. Women do not have access to political or economic power. The first effective women's group was formed in 1975 after Tahitian women's participation in the first Pacific Women's Conference held in Suva, Fiji. Tahitian women exchanged information with other women of similar background, and valuable international contacts were made. The movement to stop nuclear testing gained momentum from these interactions, from subsequent conferences, and better press coverage at home. Knowledge of environmental issues has been hampered by language barriers and literacy. The suspension of testing in April 1992 will benefit the health of Tahitians in the long term, but loss of jobs and housing will be a difficult adjustment in the short term.

Lack of autoantibody induction by mercury exposure in artisanal gold mining settings in Colombia: Findings and a review of the epidemiology literature.

PubMed

Sánchez Rodríguez, Luz Helena; Flórez-Vargas, Oscar; Rodríguez-Villamizar, Laura Andrea; Vargas Fiallo, Yolanda; Stashenko, Elena E; Ramírez, Gerardo

2015-01-01

Mercury (Hg) has been implicated as an immunotoxicant in experimental animal models, but its role in the induction of human autoimmunity remains unclear due to contradictory findings. Therefore, it has been claimed that it is important to examine other populations in order to clarify the role of Hg in these diseases. The aim of this study was to investigate whether occupational Hg exposure due to artisanal gold mining is associated with the prevalence of autoimmune biomarkers. A cross-sectional study was conducted comparing Hg-exposed gold miners (n = 164) with a control population (n = 127). Hair, blood, and 24-h urine samples were collected for measures of Hg levels, as well as of anti-nuclear antibodies (ANA) and rheumatoid factor (RF). Participants were clinically evaluated by a general practice physician, a rheumatologist, and a toxicologist. Statistically significant differences (p < 0.001) were found between Hg-exposed and non-exposed groups for all Hg biomarkers tested: blood (7.03 versus 2.46 µg Hg/L), urine (3.96 versus 1.48 µg Hg/g creatinine), and hair (0.79 versus 0.39 µg Hg/g). No difference was observed in ANA (cut-off titre of 1:80; PR = 0.93, 95% CI = 0.45-1.90) and RF (cut-off = 30 IU/mL; PR = 0.062, 95% CI = 0.03-1.08) status between the groups. In conclusion, the findings here do not support the hypothesis that Hg exposure due to artisanal gold mining activities had a significant impact on autoantibodies as biomarkers of autoimmune diseases. In a review context, the epidemiological findings were interpreted in light of the conflicting data in the literature about how Hg exposure was linked to development of autoantibodies. Validation of these findings in prospective studies is needed to firmly establish the role of Hg in development of autoimmunity in human populations.

Anti-nuclear liberals and the bomb: A comparative history of Kampf dem Atomtod and the Committee for a Sane Nuclear Policy, 1957-1963

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thiede, B.

The premises of Kampf dem Atomtod (KdA) and Citizens for a Sane Nuclear Policy (SANE) were based on nineteenth century traditions of liberal peace advocacy. Both groups gained substantial public support for their goals to prevent the nuclear armament of the Bundeswehr and to stop nuclear testing. Both organizations won well-educated middle-class and mostly white supporter. The dissertation examines the role of women: whether housewife or doctor, women stressed their special concerns as mothers. Both KdA and SANE had troubled relations with the labor movement. Their leaders hoped to gain government leaders' respect by winning a respectable, non-Communist constituency andmore » claiming their goals were reasonable ones. Government officials attacked KdA and SANE as dupes of Moscow. Many supporters left the organizations because of their strict anti-Communism. Local groups accused their leaders of lacking initative. KdA and SANE's leaders wasted time and energy rehashing issues and postponing decisions. After a period of providing initiatives and ideas local committees disintegrated. Both organizations considered education their paramount goal but their arguments primarily reached the converted, who often preferred more political action. KdA and SANE's leaders instead chose to support respectable projects based on humanitarian ideals. Since these projects offered little in the way of concrete action agendas, supporters defected to more active organizations or slipped into apathy. Neither organization achieved its national goals. Both governments generally denied them access to the policymaking process, ignored them as irrelavant, or attacked them as Communist sympathizers. While SANE and KdA were heard by those concerned by nuclear policy, and while members of SANE's National Board did help muster support for the Partial Test Ban Treaty, both organizations failed to make liberal peace values productive in the nuclear decisionmaking process.« less

Autoantibodies in chronic hepatitis C virus infection: impact on clinical outcomes and extrahepatic manifestations

PubMed Central

Gilman, Andrew J; Le, An K; Zhao, Changqing; Hoang, Joseph; Yasukawa, Lee A; Weber, Susan C; Vierling, John M; Nguyen, Mindie H

2018-01-01

Goals To examine the role that autoantibodies (auto-abs) play in chronic hepatitis C virus (HCV) regarding demographics, presence of extrahepatic manifestations and long-term outcomes in a large US cohort. Background Auto-abs have been reported to be prevalent in patients with chronic HCV infection, but data on the natural history of these patients are limited. Study The study included 1556 consecutive patients with HCV without concurrent HIV and/or HBV who had testing for antinuclear antibody (ANA), antimitochondrial antibody (AMA), antismooth muscle antibody (ASMA) and/or antiliver kidney microsomal antibody (LKM). Primary outcomes included development of cirrhosis, hepatic decompensations, hepatocellular carcinoma (HCC), mortality and/or sustained virological response (SVR) to antiviral therapy. Results A total of 388 patients tested positive for any auto-ab (ANA 21.8%, ASMA 13.3%, AMA 2.2% and LKM 1.2%). Patients who tested positive versus negative were more likely to be women (29.3% vs 20.9%, p<0.001) and less likely to achieve SVR with most treated patients receiving interferon-based therapies (37.2% vs 47.1%, p=0.031). There was no difference between groups for baseline laboratory data, disease state or rate of extrahepatic manifestations (42.8% vs 45.0%, p=0.44). Kaplan-Meier analysis revealed no statistically significant difference between groups for the 10-year development of cirrhosis, hepatic decompensations, HCC nor survival. Furthermore, auto-ab positivity was only found to be a predictor for a lower rate of SVR on multivariate analysis (adjusted OR=1.61, 95 %  CI 1.00 to 2.58, p=0.048). Conclusions In our cohort, auto-ab positivity was common, especially in women, and predicted a lower rate of SVR but otherwise had no impact on the natural history of chronic HCV or presence of extrahepatic manifestations. PMID:29755758

Optic neuromyelitis syndrome in Brazilian patients

PubMed Central

Papais-Alvarenga, R; Miranda-Santos, C; Puccioni-Sohler, M; de Almeida, A M V; Oliveira, S; De Oliveira, C A B.; Alvarenga, H; Poser, C

2002-01-01

Objectives: To report the clinical features and outcome of 24 Brazilian patients with optic neuromyelitis syndrome (ONM); discuss the underlying pathological events associated with the ONM syndrome; review the nosological situation of ONM in the group of inflammatory and demyelinating diseases of the central nervous system. Patients and Methods: Patients with ONM treated at the Hospital da Lagoa, Rio de Janeiro were studied. Demographic, clinical, magnetic resonance imaging, cerebrospinal fluid, and pathological data were analysed. Results: The study consisted of 20 women, four men of whom 10 were white and 14 Afro-Brazilians. Clinical course was recurrent in 22 cases and monophasic in two. Neurological manifestations at inclusion were: sensory impairment (66%), bilateral (41.6%) or unilateral blindness (20.8%), paraplegia or quadriplegia (37.5%). The EDSS was moderate/severe in 70.8%. The underlying pathological events were respectively pulmonary tuberculosis and upper respiratory infection in the two monophasic cases; in the 22 recurrent ONM patients: pulmonary tuberculosis (3), neurocysticercosis (1), polyarteritis nodosa (1), antinuclear antibody and rheumatoid factor (1), antiphospholipid antibody primary syndrome (1), diabetes mellitus (1), hypothyroidism (1), and amenorrhea-galactorrhea (4). Normal cerebrospinal fluid was found in 52% and an inflammatory profile in 48%. Only four recurrent ONM white patients had brain and spinal cord magnetic resonance imaging and cerebrospinal fluid findings compatible with the diagnosis of multiple sclerosis. Large lesions were seen in 62% of spinal magnetic resonance images. Six of 12 recurrent ONM Afro-Brazilian died. There were no statistical differences in the demographic data of the two ethnic groups. Afro-Brazilians were significantly more severely impaired and had a higher mortality rate than the white patients. Conclusion: These cases were classified as follows: two monophasic acute disseminated encephalomyelitis; one recurrent disseminated encephalomyelitis; three recurrent ONM associated with Hughes syndrome, autoantibodies and polyarteritis nodosa; six recurrent ONM with endocrinopathies; and finally, four muliple sclerosis cases. The remaining cases were not associated with any other condition. It would seem clear that ONM is a syndrome rather than a single disease. PMID:12235313

Neuropsychiatric manifestations and associated autoantibodies in systemic lupus erythematosus patients from Western India.

PubMed

Pradhan, Vandana; Patwardhan, Manisha; Rajadhyaksha, Anjali; Dhawale, Nivedita; Ghosh, Kanjaksha

2015-03-01

Systemic lupus erythematosus with neuropsychiatric involvement (NPSLE) can be diagnosed clinically, but there is no definite serological biomarker established. The objectives of this study were to evaluate the neuropsychiatric involvement in systemic lupus erythematosus (SLE) patients and to detect the autoantibodies associated with them. Sixty NPSLE patients along with sixty SLE patients without neuropsychiatric involvement from Maharashtra, India, were included. All patients were clinically diagnosed using the American College of Rheumatology criteria. Disease activity was assessed using the systemic lupus erythematosus disease activity index. Antinuclear antibodies (ANA), anti-dsDNA, anti-neuronal antibodies were detected by indirect immunofluorescence test. Anti-ribosomal antibodies (anti-Rib-P) were tested by ELISA. NPSLE was diagnosed in age group ranging between 10 and 20 years compared with SLE patients without neuropsychiatric involvement (21-30 years). The most frequent symptoms were psychosis (75%), followed by seizures (58%), lupus headache (40%), cognitive dysfunction (36%), mood disorder (30%), cerebrovascular disease (20%), and anxiety (18%). ANA were present in all. The prevalence of anti-Rib-P was 26.6% in NPSLE and 16.6% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found in 56.7% in NPSLE and 43.4% in SLE patients without neuropsychiatric involvement. Anti-neuronal antibodies were found to be highest in the patients of psychosis (66.6%) followed by central nerve system disease (63.63 %) and seizures (56.25%). There was an early onset of neuropsychiatric involvement. Anti-Rib-P antibodies as well as anti-neuronal antibodies did not show statistically significant correlation with neuropsychiatric manifestations in NPSLE patients.

Autoimmune liver disease in children.

PubMed

Mieli-Vergani, G; Vergani, D

2003-03-01

Autoimmune liver disorders are characterised by an inflammatory liver histology, circulating non-organ specific autoantibodies and increased levels of immunoglobulin G (IgG) in the absence of a known aetiology. They respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. Liver disorders with a likely autoimmune pathogenesis include autoimmune hepatitis (AIH) and autoimmune sclerosing cholangitis (ASC). Two types of AIH are recognised according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1-positive patients tend to present more acutely, at a younger age, and commonly have immunoglobulin A (IgA) deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological and histological presentation of ASC is often indistinguishable from that of AIH. In both, there are high IgG, non-organ specific autoantibodies and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalisation of biochemical parameters and decreased inflammatory activity on follow-up liver biopsies. However, the cholangiopathy can progress and there may be an evolution from AIH to ASC over the years, despite treatment. Whether the juvenile autoimmune form of sclerosing cholangitis and AIH are 2 distinct entities, or different aspects of the same condition, remains to be elucidated.

Low prevalence of liver-kidney microsomal autoantibodies of type 1 (LKM1) in hepatitis C seropositive subjects on Crete, Greece

PubMed Central

Drygiannakis, Dimitrios; Lionis, Christos; Drygiannakis, Ioannis; Pappas, Georgios; Kouroumalis, Elias

2001-01-01

Background Hepatitis C is a serious problem on the Greek island of Crete, where a high prevalence of antibodies against hepatitis C (anti-HCV) has recently been reported. This article reports the findings of a study carried out in Crete, which investigated the prevalence of serum autoantibodies in patients with chronic hepatitis C. Patients and Methods One hundred and forty two patients (59 men and 83 women), who were found anti-HCV seropositive in two hospitals and two Primary Health Care Centres in Crete, were eligible. Sixty healthy blood donors (46 men, 14 women), which were negative to anti-HCV, were used as the control group. They were randomly selected from those attending Rethymnon Hospital. Autoantibodies were identified using the indirect immunofluorescence (IFL) technique on human epithelial cells from larynx cancer (HEp-2 cells), rat liver-kidney-stomach substrate (CT3) and Chrithidia Luciliae (CL). Results Serum autoantibodies were detected in 104 HCV patients, yielding an overall prevalence of 73.2%. The most frequent autoantibodies were antinuclear antibodies (ANA), positive in 72 patients (50.7%). Anti-smooth muscle antibodies (ASMA) were detected in 33 patients (23.2%). Only one patient was positive for LKM1 autoantibodies. No autoantibodies were found in 38 patients (26.7%). Autoantibodies were also found in 5 out of the 60 examined healthy blood donors (8.3%). Conclusions Autoantibodies, mainly ANA and ASMA are very common in HCV seropositive patients from Crete. By contrast LKM1 autoantibodies are exceptionally rare in these patients. PMID:11418082

Catastrophic antiphospholipid syndrome: a clinical review.

PubMed

Nayer, Ali; Ortega, Luis M

2014-01-01

Catastrophic antiphospholipid syndrome (CAPS) is a rare life-threatening autoimmune disease characterized by disseminated intravascular thrombosis resulting in multiorgan failure. Directory of Open Access Journals (DOAJ), Google Scholar, PubMed (NLM), LISTA (EBSCO) and Web of Science have been searched. CAPS is due to antiphospholipid antibodies directed against a heterogeneous group of proteins that are associated with phospholipids. These autoantibodies activate endothelial cells, platelets, and immune cells, thereby promoting a proinflammatory and prothrombotic phenotype. Furthermore, antiphospholipid antibodies inhibit anticoagulants, impair fibrinolysis, and activate complements. Although CAPS can affect a variety of organs and tissues, the kidneys, lungs, central nervous system, heart, skin, liver, and gastrointestinal tract are most commonly affected. The systemic inflammatory response syndrome, likely to extensive tissue damage, accompanies CAPS. The most frequent renal manifestations are hypertension, proteinuria, hematuria, and acute renal failure.In the majority of patients with CAPS, a precipitating factor such as infection, surgery, or medication can be identified. Antiphospholipid antibodies such as lupus anticoagulant and antibodies against cardiolipin, β2-glycoprotein I, and prothrombin are serological hallmark of CAPS. Laboratory tests often reveal antinuclear antibodies, thrombocytopenia, and anemia. Despite widespread intravascular coagulation, blood films reveal only a small number of schistocytes. In addition, severe thrombocytopenia is uncommon. Histologically, CAPS is characterized by acute thrombotic microangiopathy. CAPS must be distinguished from other forms of thrombotic microangiopathies such as hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, disseminated intravascular coagulation, and heparin-induced thrombocyt openia. CAPS is associated with high morbidity and mortality. Therefore, an aggressive multidisciplinary treatment strategy is indicated. Anticoagulation, immunosuppression, plasma exchange, intravenous immunoglobulins, and anti-platelet agents, used in various combinations, have resulted in improved patient outcome.

Juvenile idiopathic arthritis profile in Turkish children.

PubMed

Yilmaz, Mustafa; Kendirli, Seval G; Altintas, Derya U; Karakoc, Gulbin B; Inal, Ayfer; Kilic, Mehmet

2008-04-01

Juvenile idiopathic arthritis (JIA) is a heterogeneous group of disorders. Publications from different countries point to differences in the disease manifestation of JIA among different populations. The aim of the present paper was to evaluate the clinical and laboratory features of JIA in Turkish children. A total of 196 JIA patients who fulfilled International League of Associations for Rheumatology (ILAR) diagnostic criteria were included in this retrospective study. The data collected were age, gender, age at disease onset and at diagnosis, and follow-up duration. Antinuclear antibody (ANA), rheumatoid factor (RF), and human leukocyte antigen B-27 were evaluated for each patient. There were 102 boys and 94 girls with a mean duration of disease of 4.1 years. The mean age at the first visit was 8.8 years, and the mean age at onset of disease was 6.8 years (range, 8 months-15 years). Polyarticular JIA was the most frequent onset type (37.2%). Other subtypes included oligoarthritis (34.2%), systemic arthritis (15.3%), psoriatic arthritis (1%), enthesitis-related arthritis (9.7%), and other arthritis (2.2%). ANA was positive in 28 patients (14.2%). Chronic uveitis occurred in two patients with oligoarthritis; and two patients with enthesitis-related arthritis had acute uveitis. Three patients (1.4%) developed amyloidosis. Compared to reports from Western countries, remarkably different features of JIA were found in Turkish children, which included higher frequency of polyarticular JIA, higher prevalence among boys, lower rate of ANA positivity and uveitis. Further studies are required to understand how genetic and environmental differences affect JIA expression.

Gender-related analysis of the clinical presentation, treatment response and outcome in patients with immune thrombocytopenia.

PubMed

Andrès, Emmanuel; Mecili, Mustapha; Fothergill, Helen; Zimmer, Jacques; Vogel, Thomas; Maloisel, Frédéric

2012-09-01

Immune thrombocytopenia (idiopathic thrombocytopenic purpura [ITP]) frequently occurs in young adults, particularly women in their third or fourth decade. The female predominance suggests that sex hormones may play a role in the different aspects of ITP. In this paper, we report a gender-related analysis of patients with ITP, specifically examining the clinical manifestations, responses to treatment and overall outcomes of the patients. We included patients with "ITP" attending the departments of onco-hematology or internal medicine B (university hospital of Strasbourg, France) between 1990 and December 2010 The gender-related analysis was retrospective. We studied in 225 consecutive cases of established ITP with a follow-up period of 1.7 to 112 months The mean age of the patients was 44 years; 156 patients were female. The analysis revealed no significant statistical differences regarding patient characteristics between the female and male groups, with the exception of the following characteristics: the bleeding score, which altered in the presence of meno- and/or metrorrhagia and hematuria in female patients (P=0.03); the presence of anemia (P=0.04); and the detection of antinuclear and/or antiphospholipid antibodies (P=0.02). During the follow-up, no statistically significant difference was found regarding outcome or treatment response in relation to gender among these 225 patients (all P>0.05). Gender does not appear to affect the manifestation of immune thrombocytopenia, the outcome or response to treatment. However, further large-scale randomized trials are needed to confirm these findings. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Organ-specific antibodies in LADA patients for the prediction of insulin dependence.

PubMed

Delitala, Alessandro P; Pes, Giovanni M; Fanciulli, Giuseppe; Maioli, Margherita; Secchi, Giannina; Sanciu, Franca; Delitala, Giuseppe; Manetti, Roberto

2016-08-01

The aim of the present study was to define the frequency of organ-specific and non-organ-specific autoantibodies in a cohort of Latent Autoimmune Diabetes in Adults (LADA) patients and to test whether multiple antibodies positivity could be a predictor of early insulin dependence. We enrolled 210 LADA and 210 type 2 diabetes mellitus (T2D) patients. In all subjects anti-islet antigen-2 (IA-2Ab), anti-thyroperoxidase (TPOAb), anti-zinc transporter 8 (ZnT8Ab), anti-nuclear (ANA), anti-parietal cell (APCA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-liver kidney microsomes (LKM), and anti-reticulin (ARA) circulating antibodies were assessed. The frequency of TPOAb, ZnT8Ab, APCA, and IA-2Ab positivity was, respectively, detected in 40.0%, 32.4%, 24.7%, and 9.5% of LADA patients, whereas their frequency was significantly lower in T2D patients (11.4%, 1.9%, 9.5%, and 0.0%, respectively, p < 0.001). The frequency of ANA was the same in both groups whereas the frequency of ASMA, ARA, AMA, and LKM was very low (range 0.0-3.3%). The presence of TPOAb associated with ZnT8Ab, IA-2Ab, or APCA allows one to predict the progression of disease with a high specificity but low sensibility. LADA patients show an increased frequency of organ- and non-organ-specific antibodies. Consequently, a screening is worthwhile in these patients. The simultaneous presence of TPOAb with ZnT8, IA-2Ab, or APCA may help differentiate clinical phenotypes and predict faster insulin dependence in LADA patients.

Nitrosative Stress and Nitrated Proteins in Trichloroethene-Mediated Autoimmunity

PubMed Central

Wang, Gangduo; Wang, Jianling; Luo, Xuemei; Ansari, G. A. Shakeel; Khan, M. Firoze

2014-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, has been linked to a variety of autoimmune diseases (ADs) including SLE, scleroderma and hepatitis. Mechanisms involved in the pathogenesis of ADs are largely unknown. Earlier studies from our laboratory in MRL+/+ mice suggested the contribution of oxidative/nitrosative stress in TCE-induced autoimmunity, and N-acetylcysteine (NAC) supplementation provided protection by attenuating oxidative stress. This study was undertaken to further evaluate the contribution of nitrosative stress in TCE-mediated autoimmunity and to identify proteins susceptible to nitrosative stress. Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, ∼250 mg/kg/day via drinking water). TCE exposure led to significant increases in serum anti-nuclear and anti-histone antibodies together with significant induction of iNOS and increased formation of nitrotyrosine (NT) in sera and livers. Proteomic analysis identified 14 additional nitrated proteins in the livers of TCE-treated mice. Furthermore, TCE exposure led to decreased GSH levels and increased activation of NF-κB. Remarkably, NAC supplementation not only ameliorated TCE-induced nitrosative stress as evident from decreased iNOS, NT, nitrated proteins, NF-κB p65 activation and increased GSH levels, but also the markers of autoimmunity, as evident from decreased levels of autoantibodies in the sera. These findings provide support to the role of nitrosative stress in TCE-mediated autoimmune response and identify specific nitrated proteins which could have autoimmune potential. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for designing therapeutic strategies. PMID:24892995

A subgroup-specific evaluation of the efficacy of intraarticular triamcinolone hexacetonide in juvenile chronic arthritis.

PubMed

Breit, W; Frosch, M; Meyer, U; Heinecke, A; Ganser, G

2000-11-01

To determine the subgroup-specific differences of intraarticular triamcinolone hexacetonide (TH) in the treatment of joint inflammation in patients with juvenile chronic arthritis (JCA). A retrospective review of 194 children of all subgroups of JCA, treated by a single or repeated TH injection between 1989 to 1994. Efficacy and duration of benefit were evaluated after a mean duration of 3, 15, 30, and 64 weeks. In all, 1439 TH injections were given to 194 patients; 368 of these were reinjections. The median duration of improvement of all injections was 74 weeks. Responses were significantly different among subgroups (p = 0.0001): there were 121 weeks of efficacy in early-onset pauciarticular JCA type I (223 injections), 47 weeks in late-onset pauciarticular JCA type II (190 injections), 105 weeks in rheumatoid factor negative polyarticular JCA (445 injections), 63 weeks in rheumatoid factor positive polyarticular JCA (127 injections), and 36 weeks in systemic JCA (413 injections). Forty-one injections were done in other rheumatic diseases. In relation to this result there were also differences with regard to joint groups, antinuclear antibody (ANA) and HLA-B27 status, and sex. Side effects were rare: infections of skin or joints were not noted; skin and lipoatrophy were seen after 15 injections, necrosis of the hip in one case, luxation of 2 shoulders of one patient, and periarticular calcification in 3 patients. Intraarticular TH is an effective therapy for inflammatory joint disease in all subgroups of JCA. The risk of major complications is low. The median duration of improvement depends on the subgroup of the disease.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

PubMed

Gheorghe, Liana; Iacob, Speranta; Gheorghe, Cristian; Iacob, Razvan; Simionov, Iulia; Vadan, Roxana; Becheanu, Gabriel; Parvulescu, Iuliana; Toader, Cristina

2004-06-01

To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.

Effects of age of onset on disease characteristics in non-segmental vitiligo.

PubMed

Solak, Berna; Dikicier, Bahar Sevimli; Cosansu, Nur C; Erdem, Teoman

2017-03-01

In patients with vitiligo, the clinical and laboratory features of the disease may vary according to time of onset. This is addressed in the literature by only a few studies with conflicting results. The aim of this study was to determine the demographic and clinical features of patients with non-segmental vitiligo and to establish the association between vitiligo and autoimmune diseases with a focus on time of disease onset. A total of 224 vitiligo patients for whom complete medical records were available were evaluated retrospectively. Demographic data, scores on the Vitiligo Area Score Index (VASI), clinical features, vitiligo disease activity, repigmentation status, presence of any accompanying autoimmune disease, antinuclear antibody (ANA) titers, serum levels of glucose, thyroid-stimulating hormone (TSH), thyroxine (T4) hormone, anti-thyroid peroxidase (anti-TPO), and anti-thyroglobulin (anti-TG) were recorded. The prevalence of halo nevi was significantly higher (P < 0.001) among children than in other patient groups. The prevalence of leukotrichia was higher in adults with adult-onset disease than in either pediatric patients or adults with childhood-onset disease (P = 0.002). Both anti-TG and anti-TPO levels were significantly higher in adults with adult-onset disease than in pediatric patients and adult patients with childhood-onset disease. The prevalence of autoimmune disease was 22.2%. Anti-TG levels were significantly higher in patients with treatment-related repigmentation than in those without repigmentation. This study shows that clinical features and associations with autoimmune disease may vary according to the age of onset of vitiligo. © 2017 The International Society of Dermatology.

The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort

PubMed Central

Mainardi-Novo, D T O; Santos, A S; Fukui, R T; Gamberini, M; Correia, M R S; Ruiz, M O; Mangueira, C L P; Matioli, S R; Vasconcelos, D M; Silva, M E R

2013-01-01

Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The −448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5′-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. PMID:23480181

The PTPN22 1858T allele but not variants in the proximal promoter region of IL-21 gene is associated with the susceptibility to type 1 diabetes and the presence of autoantibodies in a Brazilian cohort.

PubMed

Mainardi-Novo, D T O; Santos, A S; Fukui, R T; Gamberini, M; Correia, M R S; Ruiz, M O; Mangueira, C L P; Matioli, S R; Vasconcelos, D M; Silva, M E R

2013-04-01

Interleukin (IL)-21 and protein tyrosine phosphatase non-receptor 22 (PTPN22) regulate lymphocyte function and have been implicated in the pathogenesis of autoimmune diabetes. We sequenced the proximal promoter of the IL-21 gene for the first time and analysed the PTPN22 1858T polymorphism in type 1A diabetes (T1AD) patients and healthy controls (HC). We correlated the frequencies of islet and extra-pancreatic autoantibodies with genotypes from both loci. The case series comprised 612 T1AD patients and 792 HC. Genotyping of PTPN22 C1858T was performed on 434 T1AD patients and 689 HC. The -448 to +83 base pairs (bp) region of the IL-21 gene was sequenced in 309 Brazilian T1AD and 189 HC subjects. We also evaluated human leucocyte antigen (HLA) DR3/DR4 alleles. The frequencies of glutamic acid decarboxylase (GAD65), tyrosine phosphatase-like protein (IA)-2, anti-nuclear antibody (ANA), thyroid peroxidase (TPO), thyroglobulin (TG), thyrotrophin receptor autoantibody (TRAb), anti-smooth muscle (ASM) and 21-hydroxylase (21-OH) autoantibodies were higher in T1AD patients than in HC. The PTPN22 1858T allele was associated with an increased risk for developing T1AD [odds ratio (OR) = 1·94; P < 0·001], particularly in patients of European ancestry, and with a higher frequency of GAD65 and TG autoantibodies. HLA-DR3/DR4 alleles predominated in T1AD patients. A heterozygous allelic IL-21 gene variant (g.-241 T > A) was found in only one patient. In conclusion, only PTPN22 C1858T polymorphism and HLA-DR3 and/or DR4 alleles, but not allelic variants in the 5'-proximal region of the IL-21 gene were associated with T1AD risk. Patients with T1AD had increased frequencies of anti-islet-cell, anti-thyroid, anti-nuclear, anti-smooth muscle and anti-21-OH autoantibodies. The C1858T PTPN22 polymorphism was also associated with a higher frequency of GAD65 and TG autoantibodies. © 2012 British Society for Immunology.

Anti-nucleosome antibodies as a disease marker in systemic lupus erythematosus and its correlation with disease activity and other autoantibodies.

PubMed

Pradhan, Vandana D; Patwardhan, Manisha M; Ghosh, Kanjaksha

2010-01-01

Detection of anti-nucleosome antibodies (anti-nuc) in patients with systemic lupus erythematosus (SLE) has been well established and it is claimed that their presence is associated with disease activity. The aim of this study is to evaluate the incidence of anti-nuc antibodies and to correlate them with disease activity and its association with other autoantibodies like anti-nuclear antibodies (ANA), anti-double stranded DNA (anti-dsDNA), anti-histone antibodies (AHA), as well as autoantibodies to histone subfractions like H1, (H2A-H4) complex, H2B, and H3. This cross-sectional study included 100 SLE patients referred from the Rheumatology, Dermatology, and Nephrology Departments. SLE disease activity was evaluated by using SLE-Disease Activity Index (SLEDAI) score. A patient was defined as having active SLE when the SLEDAI score was more than 5.0. Fifty normal controls were also tested as a healthy control group. Anti-nuc antibodies, anti-dsDNA, and AHA were tested by Enzyme-Linked Immunosorbent Assay (ELISA) and ANA was detected by an indirect immunofluorescence test. All patients studied were in an active stage of disease and were untreated, of which 44 patients had renal biopsy-proven kidney involvement, which was categorized as lupus nephritis (LN) and 56 patients did not show any renal manifestations (SLE without LN). Anti-nuc antibodies were positive in 88%, anti-dsDNA in 80%, and AHA in 38% of the cases. ANA was positive in all SLE patients studied. None of the normal controls was found to be positive for these antibodies. Although a slightly higher incidence of autoantibodies were noted in LN, there was no statistical difference noted between LN and SLE without LN groups for anti-nuc and anti-dsDNA antibodies (p > 0.05). A higher incidence of autoantibodies to ANA specificities were noted in anti-nuc positive cases, but there was no statistical difference between anti-nuc positive and anti-nuc negative cases for ANA specificities among LN and SLE without nephritis groups (p > 0.05). Anti-nuc antibody detection could be a better tool for the diagnosis of SLE. Although there was no significant difference in LN and SLE without LN groups, this study suggests that anti-nuc detection can be useful as an additional disease activity marker to other laboratory tests.

Automated antinuclear immunofluorescence antibody screening: a comparative study of six computer-aided diagnostic systems.

PubMed

Bizzaro, Nicola; Antico, Antonio; Platzgummer, Stefan; Tonutti, Elio; Bassetti, Danila; Pesente, Fiorenza; Tozzoli, Renato; Tampoia, Marilina; Villalta, Danilo

2014-03-01

Indirect immunofluorescence (IIF) plays an important role in immunological assays for detecting and measuring autoantibodies. However, the method is burdened by some unfavorable features: the need for expert morphologists, the subjectivity of interpretation, and a low degree of standardization and automation. Following the recent statement by the American College of Rheumatology that the IIF technique should be considered as the standard screening method for the detection of anti-nuclear antibodies (ANA), the biomedical industry has developed technological solutions which might significantly improve automation of the procedure, not only in the preparation of substrates and slides, but also in microscope reading. We collected 104 ANA-positive sera from patients with a confirmed clinical diagnosis of autoimmune disease and 40 ANA-negative sera from healthy blood donors. One aliquot of each serum, without information about pattern and titer, was sent to six laboratories of our group, where the sera were tested with the IIF manual method provided by each of the six manufacturers of automatic systems. Assignment of result (pos/neg), of pattern and titer was made by consensus at a meeting attended by all members of the research team. Result was assigned if consensus for pos/neg was reached by at least four of six certifiers, while for the pattern and for the titer, the value observed with higher frequency (mode) was adopted. Seventeen ANA-positive sera and six ANA-negative sera were excluded. Therefore, the study with the following automatic instrumentation was conducted on 92 ANA-positive sera and on 34 ANA-negative sera: Aklides, EUROPattern, G-Sight (I-Sight-IFA), Helios, Image Navigator, and Nova View. Analytical imprecision was measured in five aliquots of the same serum, randomly added to the sample series. Overall sensitivity of the six automated systems was 96.7% and overall specificity was 89.2%. Most false negatives were recorded for cytoplasmic patterns, whereas among nuclear patterns those with a low level of fluorescence (i.e., multiple nuclear dots, midbody, nuclear rim) were sometimes missed. The intensity values of the light signal of various instruments showed a good correlation with the titer obtained by manual reading (Spearman's rho between 0.672 and 0.839; P<0.0001 for all the systems). Imprecision ranged from 1.99% to 25.2% and, for all the systems, it was lower than that obtained by the manual IIF test (39.1%). The accuracy of pattern recognition, which is for now restricted to the most typical patterns (homogeneous, speckled, nucleolar, centromere, multiple nuclear dots and cytoplasmic) was limited, ranging from 52% to 79%. This study, which is the first to compare the diagnostic accuracy of six systems for automated ANA-IIF reading on the same series of sera, showed that all systems are able to perform very well the task for which they were created. Indeed, cumulative automatic discrimination between positive and negative samples had 95% accuracy. All the manufacturers are actively continuing the development of new and more sophisticated software for a better definition in automatic recognition of patterns and light signal conversion in end-point titer. In the future, this may avert the need for serum dilution for titration, which will be a great advantage in economic terms and time-saving. Copyright © 2013 Elsevier B.V. All rights reserved.

Autoimmune features caused by dengue fever: a case report.

PubMed

Jardim, Denis Leonardo Fontes; Tsukumo, Daniela Miti Lemos; Angerami, Rodrigo N; Carvalho Filho, Marco Antonio de; Saad, Mário José Abdalla

2012-01-01

Dengue virus is the most important mosquito-borne viral disease in the world. Co-circulation of the four types of dengue viruses and expansion of dengue epidemic gave rise to infection enhancement and a big expansion of clinical aspects of the disease. Herein we report a case of a 25-year-old white woman with dengue fever and numerous associated autoimmune features. Our patient had proteinuria, an extensive right pleural effusion, a thin pericardial effusion and ascites. She had a low C3 level and positive antinuclear antibody; cryoglobulins were also positive. The numerous autoimmune features of this patient were a diagnostic challenge, since she was a young woman and could be easily mistaken for a rheumatologic patient in a newly open disease. Dengue infection probably was a triggering event causing an abnormal immune response. Therefore, dengue should be suspected in patients with hematological disorders and autoimmune features in endemic regions or those who have travelled to those regions.

Chronic exposure to trichloroethene causes early onset of SLE-like disease in female MRL +/+ mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai Ping; Koenig, Rolf; Boor, Paul J.

2008-04-01

Trichloroethene (TCE) exacerbates the development of autoimmune responses in autoimmune-prone MRL +/+ mice. Although TCE-mediated autoimmune responses are associated with an increase in serum immunoglobulins and autoantibodies, the underlying mechanism of autoimmunity is not known. To determine the progression of TCE-mediated immunotoxicity, female MRL +/+ mice were chronically exposed to TCE through the drinking water (0.5 mg/ml of TCE) for various periods of time. Serum concentrations of antinuclear antibodies increased after 36 and 48 weeks of TCE exposure. Histopathological analyses showed lymphocyte infiltration in the livers of MRL +/+ mice exposed to TCE for 36 or 48 weeks. Lymphocyte infiltrationmore » was also apparent in the pancreas, lungs, and kidneys of mice exposed to TCE for 48 weeks. Immunoglobulin deposits in kidney glomeruli were found after 48 weeks of exposure to TCE. Our results suggest that chronic exposure to TCE promotes inflammation in the liver, pancreas, lungs, and kidneys, which may lead to SLE-like disease in MRL +/+ mice.« less

Protein-losing enteropathy as initial manifestation of systemic lupus erythematosus.

PubMed

Carneiro, F O A A; Sampaio, L R; Brandão, L A R; Braga, L L B C; Rocha, F A C

2012-04-01

Protein-losing enteropathy is a rare manifestation of systemic lupus erythematosus. We report the case of an 18-year-old woman that presented initially with diarrhoea and anasarca. During evaluation, there was low serum albumin of 1.6 g/dl (3.5-5.2 g/dl) and a positive antinuclear antibody test (1:2560). Anti-Sm antibodies (ELISA) were positive in addition to low serum C3 of 35 mg/dl. A scintigraphy using 99mTc-labelled albumin was positive for abdominal protein loss. A diagnosis of systemic lupus erythematosus related protein-losing enteropathy was made. She was started on prednisolone 40 mg/day without amelioration; a month later, azathioprine (100 mg/day) was added, leading to normalization of serum albumin and resolution of symptoms within 4 months. After 1.5 years, the patient developed a 2.9 g 24-h proteinuria while still in remission of the protein-losing enteropathy, receiving 5 mg prednisone and 100 mg azathioprine daily.

[Arthritis of the atlanto-axial joint with inflammatory neck pain as a primary manifestation of seronegative rheumatoid arthritis].

PubMed

Haeusler, U; Dybowski, F; Wittkaemper, T A; Kisters, K; Godolias, G; Braun, J

2010-09-01

A 68-year-old woman with known degenerative joint disease suffered from increasing neck pain. Physical examination revealed painfully restricted movement of the cervical spine. Erythrocyte sedimentation rate and C-reactive protein were increased. Tests for rheumatoid factors, antinuclear, anti-citrullinated protein and anti-neutrophil cytoplasmic antibody were negative. Cervical spine x-ray showed osteochondrosis with partially bridging spondylosis at C5/C6, but there was no atlanto-axial dislocation. Magnetic resonance imaging (MRI) revealed bone marrow edema and hyperintensity of the odontoid process, but there were no indications of fissures or fracture lines. These findings indicated seronegative rheumatoid arthritis, with predominantly active atlanto-axial arthritis. After methotrexate and prednisolone had been administered the symptoms improved rapidly and inflammatory parameters returned to normal. Three months later no atlanto-axial arthritis was seen at MRI. Rheumatoid arthritis involving the atlanto-axial region should be considered in patients with persisting neck pain and signs of inflammation. Copyright Georg Thieme Verlag KG Stuttgart . New York.

Sperm, nuclear, phospholipid, and red blood cell antibodies and isotype RF in infertile couples and patients with autoimmune rheumatic diseases.

PubMed

Fichorova, R; Nakov, L; Baleva, M; Nikolov, K; Gegova, I

1996-12-01

To determine if measuring of nonorgan-specific autoantibodies is useful for better understanding and management of unexplained infertility. Sera were obtained from 70 infertile couples, 57 rheumatic patients, and 76 fertile donors. Sperm antibodies (SA) were detected by the tests of Kibrick and Friberg, anti-histones, anti-cardiolipin antibodies, and RF isotypes by ELISA, antinuclear antibodies by indirect immunofluorescence, and anti-red blood cell antibodies by Capture-R. Multiple autoimmune reactivity (both partners positive and/or more than one type of autoantibody involved), higher than naturally occurring in fertile individuals, was found in 55% of the idiopathically infertile couples. IgA-RF was the dominant autoimmune marker. SA revealed similar rates in patients with rheumatic diseases and in infertiles with or without other autoantibodies. Although no single autoimmunity marker could predict occurrence of SA, the coincidence of enhanced polyclonal autoimmunity in both partners of infertile couples might potentiate their negative effect on reproduction.

Openness initiative

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duncan, S.S.

1995-12-31

Although antinuclear campaigns seem to be effective, public communication and education efforts on low-level radioactive waste have mixed results. Attempts at public information programs on low-level radioactive waste still focus on influencing public opinion. A question then is: {open_quotes}Is it preferable to have a program focus on public education that will empower individuals to make informed decisions rather than trying to influence them in their decisions?{close_quotes} To address this question, a case study with both quantitative and qualitative data will be used. The Ohio Low-Level Radioactive Waste Education Program has a goal to provide people with information they want/need tomore » make their own decisions. The program initiated its efforts by conducting a statewide survey to determine information needed by people and where they turned for that information. This presentation reports data from the survey and then explores the program development process in which programs were designed and presented using the information. Pre and post data from the programs reveal attitude and knowledge shifts.« less

Autoantibodies: Focus on anti-DNA antibodies

PubMed Central

Almqvist, Nina; Winkler, Thomas H

2011-01-01

Ever since the days of Ehrlich and the birth of humoral immunity, self-reactivity or ‘horror autotoxicus’ as referred to by Paul Ehrlich, has been of great concern. For instance, in patients with the autoimmune disease systemic lupus erythematosus (SLE), anti-nuclear and anti-DNA antibodies have been recognized for many years. Despite this, the exact mechanism as to how the immune system fails to protect the individual and allows these autoantibodies to develop in this and other systemic autoimmune diseases remains uncertain. So how can we explain their presence? Evidence suggests that B cells expressing autoreactive antibodies do not normally arise but rather undergo negative selection as they develop. In light of this, it might seem contradictory that not all autoreactive B cell clones are eliminated, although this may not even be the intention since autoantibodies are also found in healthy individuals and may even protect from autoimmunity. Here, we will discuss autoantibodies, in particular those recognizing DNA, with regard to their reactivity and their potentially pathogenic or protective properties. PMID:21776330

Larger differences in utilization of rarely requested tests in primary care in Spain.

PubMed

Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Uris, Joaquín; Leiva-Salinas, Carlos

2015-01-01

The study was performed to compare and analyze the inter-departmental variability in the request of rarely requested laboratory tests in primary care, as opposed to other more common and highly requested tests. Data from production statistics for the year 2012 from 76 Spanish laboratories was used. The number of antinuclear antibodies, antistreptolysin O, creatinine, cyclic citrullinated peptide antibodies, deaminated peptide gliadine IgA antibodies, glucose, protein electrophoresis, rheumatoid factor, transglutaminase IgA antibodies, urinalysis and uric acid tests requested was collected. The number of test requests per 1000 inhabitants was calculated. In order to explore the variability the coefficient of quartile dispersion was calculated. The smallest variation was seen for creatinine, glucose, uric acid and urinalysis; the most requested tests. The tests that were least requested showed the greatest variability. Our study shows through a very simplified approach, in a population close to twenty million inhabitants, how in primary care, the variability in the request of laboratory tests is inversely proportional to the request rate.

Debate on the Chernobyl disaster: on the causes of Chernobyl overestimation.

PubMed

Jargin, Sergei V

2012-01-01

After the Chernobyl accident, many publications appeared that overestimated its medical consequences. Some of them are discussed in this article. Among the motives for the overestimation were anti-nuclear sentiments, widespread among some adherents of the Green movement; however, their attitude has not been wrong: nuclear facilities should have been prevented from spreading to overpopulated countries governed by unstable regimes and regions where conflicts and terrorism cannot be excluded. The Chernobyl accident has hindered worldwide development of atomic industry. Today, there are no alternatives to nuclear power: nonrenewable fossil fuels will become more and more expensive, contributing to affluence in the oil-producing countries and poverty in the rest of the world. Worldwide introduction of nuclear energy will become possible only after a concentration of authority within an efficient international executive. This will enable construction of nuclear power plants in optimally suitable places, considering all sociopolitical, geographic, geologic, and other preconditions. In this way, accidents such as that in Japan in 2011 will be prevented.

Henoch–Schönlein purpura: a clinical case with dramatic presentation

PubMed Central

Bento, João; Magalhães, Adriana; Moura, Conceição Souto; Hespanhol, Venceslau

2010-01-01

A case study involving a 55-year-old Caucasian male with end-stage glomerulosclerosis is presented here. Kidney biopsies showed no deposits on imunofluorescent microscopy. Relapsing massive haemoptysis and suspected bronchovascular malformation required lung lobectomy which revealed malformative and tortuous small blood vessels, with no vasculitis. Blood antinuclear antibodies, antineutrophil cytoplasmic antibodies and antiglomerular basement membrane antibodies were undetectable. Seric immunoglobulins and complement levels were normal. Three months later, arthralgia and joint oedema first appeared. Skin biopsy revealed vasculitis immune-reactive to immunoglobulin A. Systemic corticotherapy was then started. Two weeks later, the patient presented with abdominal pain melena and rectal bleeding (haematoquesia). Endoscopic study showed diffuse gastrointestinal haemorrhage. Angiographic study revealed diffuse lesions compatible with vasculitis and haemorrhage from multiple spots. Cyclophosphamide and then intravenous immunoglobulin were associated to treatment without response. Increasing blood loss occurred, with massive gastrointestinal haemorrhage and haemorrhagic ascitis. Death occurred due to uncontrolled diffuse bleeding. Necropsy findings showed generalised small vessels vasculitis compatible with Henoch–Schönlein purpura. PMID:22778211

EUROPattern Suite technology for computer-aided immunofluorescence microscopy in autoantibody diagnostics.

PubMed

Krause, C; Ens, K; Fechner, K; Voigt, J; Fraune, J; Rohwäder, E; Hahn, M; Danckwardt, M; Feirer, C; Barth, E; Martinetz, T; Stöcker, W

2015-04-01

Antinuclear autoantibodies (ANA) are highly informative biomarkers in autoimmune diagnostics. The increasing demand for effective test systems, however, has led to the development of a confusingly large variety of different platforms. One of them, the indirect immunofluorescence (IIF), is regarded as the common gold standard for ANA screening, as described in a position statement by the American College of Rheumatology in 2009. Technological solutions have been developed aimed at standardization and automation of IIF to overcome methodological limitations and subjective bias in IIF interpretation. In this review, we present the EUROPattern Suite, a system for computer-aided immunofluorescence microscopy (CAIFM) including automated acquisition of digital images and evaluation of IIF results. The system was originally designed for ANA diagnostics on human epithelial cells, but its applications have been extended with the latest system update version 1.5 to the analysis of antineutrophil cytoplasmic antibodies (ANCA) and anti-dsDNA antibodies. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Fukushima Nuclear Accident: Sticking to the facts, not to the political correctness

NASA Astrophysics Data System (ADS)

Ohska, Tokio

2014-05-01

The Fukushima Nuclear Reactor disaster of 2011 is still a continuing disaster three years later, although some experts have proclaimed the 4 reactors being already under control. It is surely an incredibly difficult task to properly terminate nuclear accidents. However, I should point out that the process of termination plan has been marred by too much of politics and business messing up a scientific approach to do it in a rational way. This blame must to go to both pro-nuclear and anti-nuclear power people. It makes me feel sad to see people not respecting science in executing such a difficult task. I shall list up where things went wrong with the hope that this kind of action, as I do here, would trigger people to get back to science to straighten out the execution process. I will show a few examples of published papers presenting the opinion that it is inappropriate what the Japanese government considers to be safe.

[Localized scleroderma (morphea) in childhood].

PubMed

Weibel, L

2012-02-01

Localized scleroderma or morphea is a sclerosing connective tissue disease of the skin, which may affect underlying tissues such as subcutis, muscle and bone. Many patients show extracutaneous symptoms and antinuclear antibodies, however, secondary transformation into systemic sclerosis does not occur. Localized scleroderma usually begins in childhood with a wide variation in its clinical spectrum. The linear variant is the most common subtype in children, associated with a progressive course and increased risk of complications. The disease may progress over years and result in severe functional and cosmetic disability. The etiology of localized scleroderma remains unknown. A genetic background is suspected, while triggers such as trauma, vaccinations and infections may lead to secondary immunologic phenomena. Localized scleroderma often remains unrecognized for a long time, resulting in substantial delay in treatment. The combination of systemic corticosteroids and methotrexate has been established as first-line therapy for progressive (usually linear) disease, whereas phototherapy (UVA-1 or UVB-narrow band) is suitable for adolescents with superficial circumscribed subtypes.

From Localized Scleroderma to Systemic Sclerosis: Coexistence or Possible Evolution

PubMed Central

Emanuele, Cocchiara; Amelia, Spinella; Clodoveo, Ferri

2018-01-01

Background Systemic sclerosis (SSc) and localized scleroderma (LoS) are two different diseases that may share some features. We evaluated the relationship between SSc and LoS in our case series of SSc patients. Methods We analysed the clinical records of 330 SSc patients, in order to find the eventual occurrence of both the two diseases. Results Eight (2.4%) female patients presented both the two diagnoses in their clinical histories. Six developed LoS prior to SSc; in 4/6 cases, the presence of autoantibodies was observed before SSc diagnosis. Overall, the median time interval between LoS and SSc diagnosis was 18 (range 0–156) months. Conclusions LoS and SSc are two distinct clinical entities that may coexist. Moreover, as anecdotally reported in pediatric populations, we suggested the possible development of SSc in adult patients with LoS, particularly in presence of Raynaud's phenomenon or antinuclear antibodies before the SSc onset. PMID:29666638

Systemic lupus erythematosus and renal tubular acidosis associated with hyperthyroidism. Case Report.

PubMed

Deng, Datong; Sun, Li; Xia, Tongjia; Xu, Min; Wang, Youmin; Zhang, Qiu

2016-07-01

A case of a 42-year-old female with hyperthyroidism was subsequently diagnosed to have systemic lupus erythematosus with distal RTA. The clinical examination on admission showed swelling of the knee joints and the urinalysis showed pH 6.5, pro 3+. Her blood routine results were as follows: white blood cells 1.85×109/L, platelets 100×109/L, erythrocyte 3.06×1012/L. The serum potassium was 3.11 mmol/L, 24 hour urinary electrolyte: K 68.87 mmol/24 H, antinuclear antibodies (ANA) 1:1 000, speckled pattern. The anti-double stranded DNA antibody (anti-dsDNA), anti SS-A(52) antibody and anti SS-A(60) antibody were positive. The light microscopy and immunofluorescence showed diffuse proliferative lupus nephritis. These data were compatible with the diagnosis of systemic lupus erythematosus. The diagnosis of hyperthyroidism and distal RTA is clear. This report showed that other autoimmune disease in the diagnosis of hyperthyroidism should not be ignored.

[Systemic lupus erythematosus in the pregnant patient. Implications for anesthesia].

PubMed

Pastor Tomás, E; Guillén Antón, J; Vaquerizo Gareta, A; Lirola Grajales, P; Martínez García, R; Cuartero Lobera, J

2001-03-01

A 28-year-old woman with systemic lupus erythematosus and a history of aseptic meningitis, digestive bleeding due to thrombopenia and deep venous thrombosis underwent elective cesarean for transverse presentation at 35 weeks. Preoperative blood work-up showed an antinuclear antibody titre that was slightly positive and steroid treatment was started. Surgery operation was performed with general anesthesia. The outcome was satisfactory even though serious complications can develop during the management of anesthesia in such patients. Systemic lupus erythematosus is a chronic, multisystemic disease that mainly affects women of childbearing age. Antibodies and immunocomplexes play a fundamental role. Given the multiorgan involvement in this disease, preoperative study of the lupus patient should assess all such involvement, including maternal-fetal risk, as well as consider the drug and anesthetic management to be applied. Among the clinical signs that can affect management of anesthesia are the following: aseptic meningitis, high blood pressure, pericarditis, pneumonitis and recurrent venous thrombosis. Anemia, thrombopenia and significantly altered coagulation events are common.

A prospective study on silicone breast implants and the silicone-related symptom complex.

PubMed

Contant, C M E; Swaak, A J G; Obdeijn, A I M; van der Holt, B; Tjong Joe Wai, R; van Geel, A N; Eggermont, A M M

2002-06-01

This cohort study prospectively evaluated the prevalence of the silicone-related symptom complex (SRSC) in relation to antinuclear antibodies (ANA) and magnetic resonance imaging (MRI) of silicone breast implants (SBI) 1 year after implantation. A total of 57 women undergoing mastectomy followed by immediate breast reconstruction (IBR) and SBI between March 1995 and March 1997 at the University Hospital Rotterdam/Daniel den Hoed Cancer Centre, were prospectively evaluated. Just before and 1 year after IBR the sera of these women were tested for the presence of ANA and they were screened for the prevalence of SRSC-related symptoms by questionnaire. All prostheses were evaluated by MRI 1 month and 1 year after IBR. Just before operation 11% of the women had a Sjögren score of more than 2, whereas 30% had such a score 1 year after IBR ( P = 0.01). One year postoperatively women had significantly more RA/Raynaud-related complaints: 21% preoperatively versus 40% 1 year after IBR ( P = 0.03). Within the undefined complaints-related group 19% had a score of 2 or more preoperatively and 33% 1 year after IBR ( P = 0.09). There were no new cases of ANA positivity 1 year after IBR. The linguine sign was seen by MRI in three implants: one 1 month after IBR and two 1 year after IBR. There was no relation to changes in SRSC expression and these MRI findings. In conclusion, 1 year after SBI implantation women had more SRSC-related complaints, especially Sjögren's and RA/Raynaud's. Moreover there was no correlation between elevated SRSC expression and changes in the presence of ANA or changes in MRI of the SBI 1 year after IBR.

Chronic urticaria and autoimmunity: associations found in a large population study.

PubMed

Confino-Cohen, Ronit; Chodick, Gabriel; Shalev, Varda; Leshno, Moshe; Kimhi, Oded; Goldberg, Arnon

2012-05-01

Chronic urticaria (CU) is a common disease in which most cases were considered to be idiopathic. Recent evidence indicates that at least a subset of cases of chronic idiopathic urticaria are autoimmune in origin. We aimed to characterize the association between CU, autoimmune diseases, and autoimmune/inflammatory serologic markers in a large unselected population. Data on 12,778 patients given a diagnosis of CU by either allergy or dermatology specialists during 17 years in a large health maintenance organization in Israel were collected. For each patient, we collected information on diagnosis of major, well-defined autoimmune diseases and autoimmunity- and inflammatory-related serologic markers. Similar data were collected for a control group comprised of 10,714 patients who visited dermatologists, family physicians, or allergy specialists and had no indication of CU. Having CU was associated with an increased odds ratio for hypothyroidism, hyperthyroidism, and antithyroid antibodies. Female patients with CU had a significantly higher incidence of rheumatoid arthritis, Sjögren syndrome, celiac disease, type I diabetes mellitus, and systemic lupus erythematosus, mostly diagnosed during the 10 years after the diagnosis of CU. High mean platelet volume, positive rheumatoid factor, and antinuclear antibodies were all significantly more prevalent in patients with CU. A strong association was found between CU and major autoimmune diseases. A common pathogenic mechanism is implied by the high prevalence of autoantibodies and the existence of a chronic inflammatory process expressed by the high mean platelet volume. These findings have implications for the diagnosis, management, and prognosis of patients with CU. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis.

PubMed

Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie

2016-05-01

The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome.A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome.The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%).In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options.

Etiologic characteristics and index pregnancy outcomes of recurrent pregnancy losses in Korean women

PubMed Central

Lee, Gi Su; Rhee, Jeong Ho; Kim, Jong In

2016-01-01

Objective The goal of this study was to evaluate the etiologies and clinical outcomes of Korean recurrent pregnancy loss (RPL) patients. And also, we investigated the differences between primary and secondary RPL patients, between two and three or more pregnancy losses. Methods One hundred seventy eight women diagnosed as RPL were enrolled. We performed chromosomal analysis, thyroid stimulating hormone, prolactin, blood glucose, plasminogen activator inhibitor-1, natural killer cell proportion, anticardiolipin antibodies, antiphospholipid antibodies, lupus anticoagulant, anti-β2glycoprotein-1 antibodies, antinuclear antibody, protein C, protein S, antithrombin III, homocysteine, MTFHR gene, factor V Leiden mutation, and hysterosalphingography/hysteroscopic evaluation. Results The mean age was 34.03±4.30 years, and mean number of miscarriages was 2.69±1.11 (range, 2 to 11). Anatomical cause (13.5%), chromosomal abnormalities (5.6%), and endocrine disorders (34.3%) were observed in RPL women. Elevated natural killer cell and antiphospholipid antibodies were observed in 43.3% and 7.3% each. Among of 178 women, 77 women were pregnant. After management of those women, live birth rate was 84.4% and mean gestational weeks was 37.63±5.12. Women with three or more RPL compared with women with two RPL had more common anatomical cause such as intrauterine adhesions and lower rates of spontaneous pregnancy. Compare with secondary RPL women, immunological abnormalities were more common in primary RPL. However, miscarriage rates were not different. Conclusion Immunological factor including autoimmune and alloimmune disorders was most common etiology of RPL. Inherited thrombophilia showed different patterns with other ethnic countries. Miscarriage rates were not different between primary and secondary RPL, or between two and three or more miscarriages group. PMID:27668201

A step towards standardization: A method for end-point titer determination by fluorescence index of an automated microscope. End-point titer determination by fluorescence index.

PubMed

Carbone, Teresa; Gilio, Michele; Padula, Maria Carmela; Tramontano, Giuseppina; D'Angelo, Salvatore; Pafundi, Vito

2018-05-01

Indirect Immunofluorescence (IIF) is widely considered the Gold Standard for Antinuclear Antibody (ANA) screening. However, the high inter-reader variability remains the major disadvantage associated with ANA testing and the main reason for the increasing demand of the computer-aided immunofluorescence microscope. Previous studies proposed the quantification of the fluorescence intensity as an alternative for the classical end-point titer evaluation. However, the different distribution of bright/dark light linked to the nature of the self-antigen and its location in the cells result in different mean fluorescence intensities. The aim of the present study was to correlate Fluorescence Index (F.I.) with end-point titers for each well-defined ANA pattern. Routine serum samples were screened for ANA testing on HEp-2000 cells using Immuno Concepts Image Navigator System, and positive samples were serially diluted to assign the end-point titer. A comparison between F.I. and end-point titers related to 10 different staining patterns was made. According to our analysis, good technical performance of F.I. (97% sensitivity and 94% specificity) was found. A significant correlation between quantitative reading of F.I. and end-point titer groups was observed using Spearman's test and regression analysis. A conversion scale of F.I. in end-point titers for each recognized ANA-pattern was obtained. The Image Navigator offers the opportunity to improve worldwide harmonization of ANA test results. In particular, digital F.I. allows quantifying ANA titers by using just one sample dilution. It could represent a valuable support for the routine laboratory and an effective tool to reduce inter- and intra-laboratory variability. Copyright © 2018. Published by Elsevier B.V.

Asbestos-induced autoimmunity in C57BL/6 mice.

PubMed

Pfau, Jean C; Sentissi, Jami J; Li, Sheng'ai; Calderon-Garciduenas, Lilian; Brown, Jared M; Blake, David J

2008-04-01

Environmental impacts on autoimmunity have significant public health implications. Epidemiological studies have shown associations between exposure to airborne silicates, such as crystalline silica or asbestos, and autoimmunity, but the etiology remains unclear. The purpose of this study was to test the hypothesis that asbestos could lead to a specific pattern of autoantibodies and pathology indicative of systemic autoimmune disease (SAID). Female C57Bl/6 mice were instilled intratracheally with 2 doses x 60 microg/mouse of amphibole asbestos (tremolite), wollastonite (a non-fibrogenic control fiber), or saline alone. Serum samples were collected and urine was checked for protein bi-weekly for 7 months. By 26 weeks, the asbestos-instilled animals had a significantly higher frequency of positive anti-nuclear antibody (ANA) tests compared to wollastonite and saline groups. The majority of positive ANAs showed homogeneous or combined homogeneous/speckled patterns, and tested positive for antibodies to dsDNA and SSA/Ro 52. Serum isotyping showed no significant changes in IgM, IgA, or IgG subclasses. However, there was an overall decrease in the mean IgG serum concentration in asbestos-instilled mice. IgG immune complex deposition was demonstrated in the kidneys of asbestos-instilled mice, with evidence of glomerular and tubule abnormalities suggestive of glomerulonephritis. Flow cytometry demonstrated moderate changes in the percentages of CD25+ T-suppressor cells and B1a B-cells in the superficial cervical lymph nodes of the asbestos-instilled mice. These data demonstrate that asbestos leads to immunologic changes consistent with the development of autoimmunity. This study provides a non-autoimmune prone murine model for use in future elucidation of mechanisms involved in asbestos-induced autoimmune disease.

Systemic Lupus Erythematosus and Antineutrophil Cytoplasmic Antibody-Associated Vasculitis Overlap Syndrome in Patients With Biopsy-Proven Glomerulonephritis

PubMed Central

Jarrot, Pierre-Andre; Chiche, Laurent; Hervier, Baptiste; Daniel, Laurent; Vuiblet, Vincent; Bardin, Nathalie; Bertin, Daniel; Terrier, Benjamin; Amoura, Zahir; Andrés, Emmanuel; Rondeau, Eric; Hamidou, Mohamed; Pennaforte, Jean-Loup; Halfon, Philippe; Daugas, Eric; Dussol, Bertrand; Puéchal, Xavier; Kaplanski, Gilles; Jourde-Chiche, Noemie

2016-01-01

Abstract The aim of the study was to report the clinical, biological, and pathological characteristics of patients with glomerulonephritis (GN) secondary to systemic lupus erythematosus (SLE)/antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) overlap syndrome. A nationwide survey was conducted to identify cases of SLE/AAV overlap syndrome. Data were collected from SLE and AAV French research groups. Inclusion criteria were diagnosis of both SLE and AAV according to international classification criteria and biopsy-proven GN between 1995 and 2014. Additional cases were identified through a systematic literature review. A cohort of consecutive biopsy-proven GN was used to study the prevalence of overlapping antibodies and/or overlap syndrome. The national survey identified 8 cases of SLE/AAV overlap syndrome. All patients were female; median age was 40 years. AAV occurred before SLE (n = 3), after (n = 3), or concomitantly (n = 2). Six patients had rapidly progressive GN and 3/8 had alveolar hemorrhage. All patients had antinuclear antibodies (ANA); 7/8 had p-ANCA antimyeloperoxidase (MPO) antibodies. Renal biopsies showed lupus nephritis (LN) or pauci-immune GN. Remission was obtained in 4/8 patients. A literature review identified 31 additional cases with a similarly severe presentation. In the GN cohort, ANCA positivity was found in 30% of LN, ANA positivity in 52% of pauci-immune GN, with no correlation with pathological findings. The estimated prevalence for SLE/AAV overlap syndrome was 2/101 (2%). In patients with GN, SLE/AAV overlap syndrome may occur but with a low prevalence. Most patients have an aggressive renal presentation, with usually both ANA and anti-MPO antibodies. Further studies are needed to assess shared pathogenesis and therapeutic options. PMID:27258503

Analysis of prognostic factors associated with longitudinally extensive transverse myelitis.

PubMed

Sepúlveda, María; Blanco, Yolanda; Rovira, Alex; Rio, Jordi; Mendibe, Mar; Llufriu, Sara; Gabilondo, Iñigo; Villoslada, Pablo; Castilló, Joaquin; Corral, Juan; Ayuso, Teresa; Iñiguez, Cristina; Santos, Sonia; Guijarro, Cristina; Ramió-Torrentà, Lluis; Sempere, Angel P; Olascoaga, Javier; Graus, Francesc; Montalban, Xavier; Saiz, Albert

2013-05-01

The aim of this study is to report the clinical profile and outcome of longitudinally extensive transverse myelitis (LETM). We prospectively studied adult patients who presented with LETM from January 2008 to December 2011. Information on demographic, clinical course, magnetic resonance imaging (MRI) and outcome was collected. HLA-DRB1 genotype was compared with those of 225 normal controls and patients with MS (228) and neuromyelitis optica (NMO) (22). In total, 23 patients (16 female) with a median age of 44.5 years (range: 20-77 years) were included. Most (74%) had moderate-severe disability at nadir (48% non-ambulatory), normal/non-multiple sclerosis (MS) brain MRI (96%) and a median MRI cord lesion of 5 vertebral segments (range: 3-19). Laboratory analysis showed cerebrospinal fluid pleocytosis (45%), NMO-IgG (9%), antinuclear antibodies (70%), and genotype HLA-DRB1*13 (57%). The frequency of DRB1*13 genotype was higher compared with controls (p=0.002), MS (p=0.001) and NMO (p=0.003) patients. After a median follow-up of 32 months, one patient converted to MS, two had relapsing LETM with NMO-IgG, and 20 remained as idiopathic with recurrences in four (20%). Twelve (52%) patients recovered with minimal disability (Expanded Disability Status Scale (EDSS) ≤2.5) and three (13%) remained wheelchair dependent. Disability at nadir was associated with the final outcome and extension of the spinal cord lesion with risk of recurrence. Recurrence was not associated with worse outcome. Inflammatory LETM is mostly idiopathic with a good outcome. It includes a relatively homogenous group of patients with an overrepresentation of the HLA-DRB1*13 genotype. EDSS at nadir is a predictor of the final outcome and extension of the myelitis of the recurrence risk.

Atomic-powered democracy: Policy against politics in the quest for American nuclear energy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, R.W.

This dissertation focuses on the relationship of American nuclear energy to democracy. It examines whether the nuclear policy processes have furthered the legitimacy-government accountability and citizen participation-which the democratic institutes are based. Nuclear policy and its institutions have placed severe limitations on democratic practices. Contravened democracy is seen most clearly in the decoupling of policy from politics. Decoupling refers to the weakening of institutional linkages between citizens and government, and to the erosion of the norms that ground liberal democracy. Decoupling is manifested in policy centralization, procedural biases, technical rationality, and the spatial displacement of conflict. Decoupling has normative implications:more » While federal accountability was limited and citizen participation was shackled, other major groups enjoyed privileged access to policy making. The decoupling of nuclear policy from politics arose within the context of US liberal-democratic capitalism. The federal government pursued its own goals of defense and world leadership. Yet, it was not structurally autonomous from the hegemony of the political-economic context. Economically, the Atomic Energy Act did not permit federal agencies to directly invest in power plant construction, and did not authorize them to commercially generate electricity. Private industry was structurally placed to domesticate the atom. Politically, the liberal-democratic system hampered an unquestioning pursuit of atomic energy. Federal institutions have been forced to heed some of the anti-nuclear concerns. The pervasive influence of the US political economy on nuclear policy has come to transgress democracy. Nuclear power's growth faltered during the 1970s. The political and economic constraints on federal actions have limited the means available to revive a becalmed nuclear industry; this has exerted strong pressure on federal institutions to decouple policy from participation.« less

Characterization and differentiation of autoimmune versus viral liver involvement in patients with Sjögren's syndrome.

PubMed

Ramos-Casals, Manuel; Sánchez-Tapias, Jose-María; Parés, Albert; Forns, Xavier; Brito-Zerón, Pilar; Nardi, Norma; Vazquez, Pilar; Vélez, Desirée; Arias, Isabel; Bové, Albert; Plaza, Joan; Rodés, Juan; Font, Josep

2006-08-01

To analyze the prevalence and clinical significance of liver involvement in patients with Sjögren's syndrome (SS), focusing on the characterization and differentiation of autoimmune versus chronic viral liver disease. We investigated liver involvement (clinical signs, analytical data, chronic viral infections, and autoantibodies) in 475 consecutive patients with SS. All patients fulfilled 4 or more of the 1993 European Community Study Group criteria for SS. Liver involvement was detected in 129 (27%) patients. After ruling out chronic illnesses or use of hepatotoxic drugs, the main etiologies were chronic viral liver disease in 64 (13%) cases [chronic hepatitis C virus (HCV) infection in 63 and HBV infection in one] and autoimmune liver diseases in 24 (5%; primary biliary cirrhosis in 16 patients and type-1 autoimmune hepatitis in 8). The analytical liver profile was not useful in differentiating between viral and autoimmune liver disease. In contrast, patients with SS and autoimmune liver disease presented higher mean values of erythrocyte sedimentation rate (p = 0.044), circulating gammaglobulins (p = 0.007), and a higher prevalence of antinuclear antibodies (p < 0.001), antimitochondrial antibodies (p < 0.001), anti-smooth muscle antibodies (p = 0.026), anti-Ro/SSA (p < 0.001), and anti-La/SSB (p = 0.01), while patients with chronic viral liver disease had a higher frequency of cryoglobulinemia (p < 0.001) and hypocomplementemia (p < 0.001). Chronic viral liver disease (associated overwhelmingly with HCV) was the main cause of liver involvement in our patients with SS, with a prevalence of 13%, nearly 3-fold greater than that observed for autoimmune liver involvement. The immunological pattern played a key role in the differentiation of viral (predominance of cryoglobulins and low complement levels) and autoimmune (higher frequency of autoantibodies) liver involvement.

Sensitivity and specificity of ANA and anti-dsDNA in the diagnosis of systemic lupus erythematosus: a comparison using control sera obtained from healthy individuals and patients with multiple medical problems.

PubMed

Wichainun, Ramjai; Kasitanon, Nuntana; Wangkaew, Suparaporn; Hongsongkiat, Sith; Sukitawut, Waraporn; Louthrenoo, Worawit

2013-12-01

Antinuclear antibodies (ANA) and anti-double stranded DNA (anti-dsDNA) are often tested as a screening tool in patients with suspected systemic lupus erythematosus or connective tissue diseases. ANA can be seen in healthy controls (HC) and patients with multiple medical problems (MMP). To determine the sensitivity and specificity of ANA and anti-dsDNA in SLE patients, using sera from HC and MMP patients. Serum samples from HC, MMP and SLE patients, 100 in each group, were analyzed for the presence of ANA and anti-dsDNA, by indirect immunofluorescent assay, using a HEp-2 cell and Crithidia luciliae as substrates, respectively. The prevalence of ANA at a titer of ≥1:80 and ≥ 1:160 was 8% and 4%, respectively, in HC; and it was 12% and 6% respectively, in MMP patients. The prevalence of anti-dsDNA was 0% in HC and 3% in MMP patients. When using HC sera for the diagnosis of SLE, the sensitivity of ANA at a titer of ≥ 1:80 and ≥ 1:160 was 98% and 90%, respectively, with specificity of 92% and 96%, respectively. The specificity decreased to 88% and 94%, respectively, when using sera from MMP patients. The specificity of anti-dsDNA was 100% and 97%, when using sera from HC and MMP patients, respectively. ANA and anti-dsDNA gave high sensitivity and high specificity in patients with SLE, even when using MMP patient's sera as controls. Physicians should take care in interpreting ANA and anti-dsDNA results in MMP patients who do not have signs or symptoms of SLE or connective tissue diseases.

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

PubMed Central

Wang, Gangduo; Wang, Jianling; Ma, Huaxian; Ansari, G.A.S.; Khan, M. Firoze

2017-01-01

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL+/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL+/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCE exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. PMID:23993974

Increased Disease Activity is Associated with Altered Sleep Architecture in an Experimental Model of Systemic Lupus Erythematosus

PubMed Central

Palma, Beatriz Duarte; Tufik, Sergio

2010-01-01

Study Objectives: The aim of this study was to evaluate sleep patterns during the course of the disease in (NZB/NZW)F1 mice, an experimental model of systemic lupus erythematosus (SLE). Design: Female mice were implanted with electrodes for chronic recording of sleep-wake cycles during the entire experimental phase (9, 19, and 29 weeks of age). The disease course was also assessed. At each time-point, blood samples were collected from the orbital plexus to evaluate serum antinuclear antibodies (ANA), which are important serologic parameters of disease evolution. Pain perception was also evaluated. Measurements and Results: During the dark phase, (NZB/NZW)F1 mice aged 19 weeks spent more time in sleep, and, as a consequence, the total waking time was lower when compared with earlier periods. An augmented number of sleep-stage transitions and microarousals were observed at the 29th week of life in both light and dark phases. At this same time-point, the mice showed lower pain thresholds than they had at 9 weeks of life. The disease status was confirmed; the entire group of mice at 29 weeks of life showed positive ANA with high titer levels. Conclusions: The sleep-recording data showed that, during the progress and severe phases of the disease (19 and 29 wks of age, respectively), sleep architecture is altered. According to these results, increased sleep fragmentation, disease activity, and pain sensitivity are features observed in these mice, similar to symptoms of SLE. Citation: Palma BD; Tufik S. Increased disease activity is associated with altered sleep architecture in an experimental model of systemic lupus erythematosus. SLEEP 2010;33(9):1244-1248. PMID:20857872

Systemic lupus erythematosus in an African Caribbean population: incidence, clinical manifestations, and survival in the Barbados National Lupus Registry.

PubMed

Flower, Cindy; Hennis, Anselm J M; Hambleton, Ian R; Nicholson, George D; Liang, Matthew H

2012-08-01

To assess the epidemiology, clinical features, and outcomes of systemic lupus erythematosus (SLE) in the predominantly African Caribbean population of Barbados. A national registry of all patients diagnosed with SLE was established in 2007. Complete case ascertainment was facilitated by collaboration with the island's sole rheumatology service, medical practitioners, and the lupus advocacy group. Informed consent was required for inclusion. Between January 1, 2000 and December 31, 2009, there were 183 new cases of SLE (98% African Caribbean) affecting 172 women and 11 men for unadjusted annual incidence rates of 12.21 (95% confidence interval [95% CI] 10.46-14.18) and 0.84 (95% CI 0.42-1.51) per 100,000 person-years, respectively. Excluding pediatric cases (ages <18 years), the unadjusted incidence rate among women was 15.14 per 100,000 person-years. The principal presenting manifestations were arthritis (84%), nephritis (47%), pleuritis (41.5%), malar rash (36.4%), and discoid lesions (33.1%). Antinuclear antibody positivity was 95%. The overall 5-year survival rate was 79.9% (95% CI 69.6-87.1), decreasing to 68% in patients with nephritis. A total of 226 persons with SLE were alive at the end of the study for point prevalences of 152.6 (95% CI 132.8-174.5) and 10.1 (95% CI 5.4-17.2) per 100,000 among women and men, respectively. Rates of SLE in Barbadian women are among the highest reported to date, with clinical manifestations similar to African American women and high mortality. Further study of this population and similar populations of West African descent might assist our understanding of environmental, genetic, and health care issues underpinning disparities in SLE. Copyright © 2012 by the American College of Rheumatology.

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Medication use in juvenile uveitis patients enrolled in the Childhood Arthritis and Rheumatology Research Alliance Registry.

PubMed

Henderson, Lauren A; Zurakowski, David; Angeles-Han, Sheila T; Lasky, Andrew; Rabinovich, C Egla; Lo, Mindy S

2016-02-16

There is not yet a commonly accepted, standardized approach in the treatment of juvenile idiopathic uveitis when initial steroid therapy is insufficient. We sought to assess current practice patterns within a large cohort of children with juvenile uveitis. This is a cross-sectional cohort study of patients with uveitis enrolled in the Childhood Arthritis and Rheumatology Research Alliance (CARRAnet) registry. Clinical information including, demographic information, presenting features, disease complications, and medications were collected. Chi-square and Fisher's exact tests were used to assess for associations between medications and clinical characteristics. Ninety-two children with idiopathic and 656 with juvenile idiopathic arthritis (JIA)-associated uveitis were identified. Indication (arthritis or uveitis) for medication use was not available for JIA patients; therefore, detailed analysis was limited to children with idiopathic uveitis. In this group, 94 % had received systemic steroids. Methotrexate (MTX) was used in 76 % of patients, with oral and subcutaneous forms given at similar rates. In multivariable analysis, non-Caucasians were more likely to be treated initially with subcutaneous MTX (P = 0.003). Of the 53 % of patients treated with a biologic DMARD, all received a tumor necrosis factor (TNF) inhibitor. TNF inhibitor use was associated with a higher frequency of cataracts (52 % vs 21 %; P = 0.001) and antinuclear antibody positivity (49 % vs 29 %; P = 0.04), although overall complication rates were not higher in these patients. Among idiopathic uveitis patients enrolled in the CARRAnet registry, MTX was the most commonly used DMARD, with subcutaneous and oral forms equally favored. Patients who received a TNF inhibitor were more likely to be ANA positive and have cataracts.

Interface dermatitis in skin lesions of Kikuchi-Fujimoto's disease: a histopathological marker of evolution into systemic lupus erythematosus?

PubMed

Paradela, S; Lorenzo, J; Martínez-Gómez, W; Yebra-Pimentel, T; Valbuena, L; Fonseca, E

2008-12-01

Kikuchi's disease (KD) is a self-limiting histiocytic necrotizing lymphadenitis (HNL). Cutaneous manifestations are frequent and usually show histopathological findings similar to those observed in the involved lymph nodes. HNL with superposed histological features to KD has been described in patients with lupus erythematosus (LE), and a group of healthy patients previously reported as having HNL may evolve into LE after several months. Up to date, features to predict which HNL patients will have a self-limiting disease and which could develop LE have been not identified. In order to clarify the characteristics of skin lesions associated with KD, we report a case of HNL with evolution into systemic lupus erythematosus (SLE) and a review of previous reports of KD with cutaneous manifestations. A 17-year-old woman presented with a 4-month history of fever and generalised lymphadenopathy. A diagnosis of HNL was established based on a lymph node biopsy. One month later, she developed an erythematoedematous rash on her upper body, with histopathological findings of interface dermatitis. After 8 months, anti-nuclear antibodies (ANA) at titre of 1/320, anti-DNA-ds antibodies and marked decrease of complement levels were detected. During the following 2 years, she developed diagnostic criteria for SLE, with arthralgias, pleuritis, aseptic meningitis, haemolytic anaemia and lupus nephritis. To our knowledge, 27 cases of nodal and cutaneous KD have been reported, 9 of which later developed LE. In all these patients, the skin biopsy revealed interface dermatitis. Skin biopsy revealed a pattern of interface dermatitis in all reviewed KD cases, which evolved into LE. Even this histopathological finding was not previously considered significant; it might be a marker of evolution into LE.

Autoantibody profile in the experimental model of scleroderma induced by type V human collagen

PubMed Central

Callado, Maria R M; Viana, Vilma S T; Vendramini, Margarete B G; Leon, Elaine P; Bueno, Cleonice; Velosa, Ana P P; Teodoro, Walcy R; Yoshinari, Natalino H

2007-01-01

The aim of this study is to evaluate the humoral autoimmune response in the experimental model of systemic sclerosis (SSc) induced by human type V collagen (huCol V). New Zealand rabbits were immunized with huCol V in Freund's complete adjuvant (FCA) and boosted twice with 15 days intervals with huCol V in Freund's incomplete adjuvant. Control groups included animals injected only with FCA or bovine serum albumin. Bleeding was done at days 0, 30, 75 and 120. Tissue specimens were obtained for histopathological investigation. Serological analysis included detection of antibodies against huCol V and anti-topoisomerase I (Anti-Scl70) by enzyme-linked immunosorbent assay, antinuclear antibodies (ANA) by indirect immunofluorescence, and rheumatoid factor (RF) by a latex agglutination test. Target antigens were characterized by immunoblot. Histological analysis revealed extracellular matrix remodeling with fibrosis and vasculitis. Anti-Scl70 and ANA were detected as early as 30 days in all huCol V animals. The universal ANA staining pattern was Golgi-like. This serum reactivity was not abolished by previous absorption with huCol V. Characterization of the target antigen by immunoblot revealed two major protein fractions of 175 000 and 220 000 MW. Similarly to ANA, there was a gradual increase of reactivity throughout the immunization and also it was not abolished by preincubation of serum samples with huCol V. RF testing was negative in hyperimmune sera. Conclusion: The production of autoantibodies, including anti-Scl70, a serological marker for SSc associated with histopathological alterations, validates huCol V induced-experimental model and brings out its potential for understanding the pathophysiology of SSc. PMID:17442023

Rheumatic Disease Autoantibodies in Patients with Autoimmune Thyroid Diseases.

PubMed

Nisihara, Renato; Pigosso, Yasmine; Prado, Nathalia; Utiyama, Shirley R R; Carvalho, Gisah; Skare, Thelma

2018-06-04

Patients with autoimmune thyroid diseases (ATD) such as Graves' disease (GD) and Hashimoto thyroiditis (HT) may have non-organ specific autoantibodies such as ANA (antinuclear antibodies) and RF (rheumatoid factor). To study the prevalence of rheumatic autoantibodies in a group of ATD patients without known rheumatic diseases and to evaluate its association with the patients' epidemiological and treatment profile. To follow positive non-organ specific autoantibody-positive ATD individuals to investigate whether they will develop a rheumatic disorder. A sample of 154 ATD patients (70 HT and 84 GD; mean age 45.3 ± 14.2) had determination of ANA by immunofluorescence, using hep-2 cells as substrate, extractable nuclear antigen (ENA) profile by ELISA kits and RF by latex agglutination. Epidemiological and treatment profile were obtained through chart review. These patients were followed for the mean period of five years, between 2010 to 2015. Positive ANA was found in 17.5% (27/154) of the patients: anti-Ro/SS-A in 4/154 (2.5%); anti-RNP in 4/154 (2.5%) and anti-La/SS-B in 3/154 (1.9%). None had anti-Sm antibodies. RF was detected in 12/154 (7.7%) of ATD patients and was more common in older individuals (p = 0.007). There was a positive association between the presence of RF and ANA (p = 0.03; OR = 3.89; 95% CI = 1.1-13.3). None of the patients with positive autoantibodies developed clinical rheumatic diseases during the period of observation. We found rheumatic autoantibodies in 17.5% of ATD patients without rheumatic diseases. None of them were associated with the appearance of clinical rheumatic disorder during the period of five years. ©2018The Author(s). Published by S. Karger AG, Basel.

Efficacy and Safety of Epratuzumab in Moderately to Severely Active Systemic Lupus Erythematosus: Results From Two Phase III Randomized, Double-Blind, Placebo-Controlled Trials.

PubMed

Clowse, Megan E B; Wallace, Daniel J; Furie, Richard A; Petri, Michelle A; Pike, Marilyn C; Leszczyński, Piotr; Neuwelt, C Michael; Hobbs, Kathryn; Keiserman, Mauro; Duca, Liliana; Kalunian, Kenneth C; Galateanu, Catrinel; Bongardt, Sabine; Stach, Christian; Beaudot, Carolyn; Kilgallen, Brian; Gordon, Caroline

2017-02-01

Epratuzumab, a monoclonal antibody that targets CD22, modulates B cell signaling without substantial reductions in the number of B cells. The aim of this study was to report the results of 2 phase III multicenter randomized, double-blind, placebo-controlled trials, the EMBODY 1 and EMBODY 2 trials, assessing the efficacy and safety of epratuzumab in patients with moderately to severely active systemic lupus erythematosus (SLE). Patients met ≥4 of the American College of Rheumatology revised classification criteria for SLE, were positive for antinuclear antibodies and/or anti-double-stranded DNA antibodies, had an SLE Disease Activity Index 2000 (SLEDAI-2K) score of ≥6 (increased disease activity), had British Isles Lupus Assessment Group 2004 index (BILAG-2004) scores of grade A (severe disease activity) in ≥1 body system or grade B (moderate disease activity) in ≥2 body systems (in the mucocutaneous, musculoskeletal, or cardiorespiratory domains), and were receiving standard therapy, including mandatory treatment with corticosteroids (5-60 mg/day). BILAG-2004 grade A scores in the renal and central nervous system domains were excluded. Patients were randomized 1:1:1 to receive either placebo, epratuzumab 600 mg every week, or epratuzumab 1,200 mg every other week, with infusions delivered for the first 4 weeks of each 12-week dosing cycle, for 4 cycles. Patients across all 3 treatment groups also continued with their standard therapy. The primary end point was the response rate at week 48 according to the BILAG-based Combined Lupus Assessment (BICLA) definition, requiring improvement in the BILAG-2004 score, no worsening in the BILAG-2004 score, SLEDAI-2K score, or physician's global assessment of disease activity, and no disallowed changes in concomitant medications. Patients who discontinued the study medication were classified as nonresponders. In the EMBODY 1 and EMBODY 2 trials of epratuzumab, 793 patients and 791 patients, respectively, were randomized, 786 (99.1%) and 788 (99.6%), respectively, received study medication, and 528 (66.6%) and 533 (67.4%), respectively, completed the study. There was no statistically significant difference in the primary end point between the groups, with the week 48 BICLA response rates being similar between the epratuzumab groups and the placebo group (response rates ranging from 33.5% to 39.8%). No new safety signals were identified. In patients with moderate or severely active SLE, treatment with epratuzumab + standard therapy did not result in improvements in response rates over that observed in the placebo + standard therapy group. © 2016 The Authors. Arthritis & Rheumatology published by Wiley Periodicals, Inc. on behalf of the American College of Rheumatology.

Apolipoprotein E-knockout mice show increased titers of serum anti-nuclear and anti-dsDNA antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuehai; Huang, Ziyang, E-mail: huangziyang666@126.com; Lu, Huixia

2012-07-13

Highlights: Black-Right-Pointing-Pointer Titers of ANA and anti-dsDNA antibodies were higher in ApoE{sup -/-} than C57B6/L mice. Black-Right-Pointing-Pointer Spleen was greater and splenocyte apoptosis lower in ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer Level of TLR4 was lower in spleen tissue of ApoE{sup -/-} than B6 mice. Black-Right-Pointing-Pointer The TLR4 pathway may participate in maintaining the balance of splenocyte apoptosis. Black-Right-Pointing-Pointer The TLR4 pathway may participate in antibody production in spleen tissue. -- Abstract: Apolipoprotein E-knockout (ApoE{sup -/-}) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE{sup -/-}more » mice. The spleens of all ApoE{sup -/-} and C57BL/6 (B6) mice were weighed. The serum IgG level and titers of anti-nuclear antibody (ANA) and anti-double-stranded DNA (anti-dsDNA) antibody were assayed by ELISA. Apoptosis of spleen tissue was evaluated by TUNEL. TLR4 level in spleen tissue was tested by immunohistochemistry and Western blot analysis. Levels of MyD88, p38, phosphorylated p38 (pp38), interferon regulatory factor 3 (IRF3) and Bcl-2-associated X protein (Bax) in spleen tissue were detected by Western blot analysis. We also survey the changes of serum autoantibodies, spleen weight, splenocyte apoptosis and the expressions of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue in male ApoE{sup -/-} mice after 4 weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE{sup -/-} mice showed splenomegaly and significantly increased serum level of IgG and titers of ANA and anti-dsDNA antibody as compared with B6 mice. Splenocyte apoptosis and the expression of TLR4, MyD88, pp38, IRF3 and Bax in spleen tissue were significantly lower in ApoE{sup -/-} than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE{sup -/-} spleen tissue. The down-regulation of TLR4 signal molecules induced by LPS led to decreased expression of Bax and increased serum titers of ANA and anti-dsDNA antibody. Therefore, the TLR4 signal pathway may participate in maintaining the balance of splenocyte apoptosis and autoantibody production in ApoE{sup -/-} mice.« less

Refractory immune thrombocytopenia successfully treated with high-dose vitamin D supplementation and hydroxychloroquine: two case reports

PubMed Central

2013-01-01

Introduction Immune thrombocytopenic purpura is thought to be characterized by an immune response against the host’s own platelets. If the thrombocytopenia is severe, patients are initially treated with high-dose steroids. Other more toxic second line treatments are considered if steroids fail. Here, we report the case of two patients in whom conventional treatment was unsuccessful but who responded to hydroxychloroquine and high-dose vitamin D replacement therapy. To the best of our knowledge, this is the first description of successful treatment for immune thrombocytopenia with high-dose vitamin D and hydroxychloroquine. Case presentation Case 1: We report the case of a 79-year-old Caucasian man who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and clinically was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with profound life-threatening thrombocytopenia. There was no evidence of underlying malignancy. The patient’s platelet count significantly increased with vitamin D and hydroxychloroquine treatment, but upon vitamin D discontinuation his platelet levels plummeted. Hydroxychloroquine therapy was maintained throughout treatment. With reinstitution of high-dose vitamin D therapy, platelet counts were restored to normal levels. Case 2: We also report the case of an 87-year-old Caucasian woman who presented with high titer antinuclear antibodies, positive anti-SSA/Ro autoantibodies and was felt to have an overlap of systemic lupus erythematosus and/or Sjögren’s syndrome with immune thrombocytopenia; she also had severely low levels of 25-hydroxy vitamin D (17ng/mL). There was no evidence of underlying malignancy. She responded to high-dose vitamin D replacement and hydroxychloroquine treatment, thereby alleviating the need for high-dose steroid treatment. She remains in remission while taking vitamin D, hydroxychloroquine and very low-dose prednisone. No untoward side effects were observed in either patient. Conclusions In our two case reports, we found an association between vitamin D deficiency and immune thrombocytopenia where platelet levels responded to vitamin D treatment and hydroxychloroquine but not to prednisone. We believe there may be synergism between vitamin D supplementation and hydroxychloroquine. The mechanism by which high-dose vitamin D results in increased platelet counts in immune thrombocytopenia patients is unknown. However, vitamin D has long been thought to play an immunomodulatory role, which may include a dampened immune response in patients with immune thrombocytopenia or other autoimmune diseases. PMID:23556539

An Autoimmune Myositis-Overlap Syndrome Associated With Autoantibodies to Nuclear Pore Complexes

PubMed Central

Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J.; Targoff, Ira N.; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

2014-01-01

Abstract Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr). By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults. Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1∗0501 allele associated with an increased risk for autoimmune myositis. In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an “anti-nup syndrome.” PMID:25500708

[Pathologico-anatomic contribution to antibody detection in immunopathologic diseases].

PubMed

Nozicka, Z

1991-01-01

Results of twenty years experience with identification of anti organ autoantibodies occurring mainly during autoimmune diseases are presented. Cryostat sections from human cadaver tissue and albino-rat kidneys were used for the detection of the above mentioned antibodies, by method of two-step (indirect) immunofluorescence. The study describes working schedule of a newly established subspeciality of pathological anatomy--the "histoserology". The main aim of the study was investigate the occurrence of autoantibodies and to asses the correlation between these findings and health condition of patients. The following antibodies were evaluated: antibodies against epithelia and colloid of thyroid gland, the antibody against parietal cells of stomach mucosa, antibodies against striated ducts of salivary gland and basal elements in its excretory ducts, the antibody against suprarenal cortical elements, the antibody against parathyreoidea, the antibody against smooth muscle cells, anti brush-border antibody, and the anti-nuclear factor as well as the antibodies against intercellular substance and basement membrane of epidermis. Antibody against thyroid gland coloid appears to be of diagnostic value for recognizing of Hashimoto and focal thyroiditis. The finding of antibody against parietal cells indicates the probability of pernicious trait in diagnostically unclear anaemias. On the other hand the finding of such antibody is not very useful in classification of gastritis and its subtyping. The appearance of the phenomenon of "shaggy rim" during the assay for antinuclear factor seems to be very reliable for verification of systemic lupus. The antibody against salivary gland striated ducts does not give fundamental support for diagnosis of Sjögren's disease. Very interesting immunopathological phenomenon is an occurrence of antibody binding to basal cells of salivary gland excretory ducts. To our knowledge, this phenomenon is rather typical for the antibody against cytokeratin polypeptide No 13 and 16. The finding of the antibody against suprarenal gland cortical elements seems to be essential for diagnosis of chronic nonspecific epinephritis since its appearance is mostly without false positivities. Also the antibodies against epidermal intercellular and basement membrane show similar high specificity. Both these antibodies unfortunately often fail and for their high number of false negative results are solely of affirmative importance, since their lack is evidently unwarranted for exclusion of considered disease. Both the findings of antibody against smooth muscle cells and against mitochondria are usefull for the diagnosis of liver lesions especially those of primary biliary cirrhosis. Anti brush-border antibody essentially assists the diagnosis of Crohn's disease and works to differentiate it from ulcerative colitis. Antireticulin antibodies counts frequently for the diagnosis of celiakia.(ABSTRACT TRUNCATED AT 400 WORDS)

Image analysis of fibrosis in labial salivary glands of patients with systemic autoimmune diseases. Close correlation of lobular fibrosis to seropositive rheumatoid arthritis and increased anti-CCP and RF titres in the serum.

PubMed

Katona, Krisztián; Farkas, Nelli; Kneif, Mária; SütŐ, Gábor; Berki, Tímea; Balatonyi, Balázs; Tornóczky, Tamás

2018-06-01

Lobular fibrosis in labial salivary glands of patients with systemic autoimmune disease is a rarely examined and rather neglected histological change. Its significance and disease association is poorly understood. Our aim was to explore the clinical correlations of fibrosis in labial salivary gland samples using objective methods and laboratory parameters. Labial salivary gland samples from more than 300 patients over a 3-year period were selected from the archives of the pathology department, histologically examined, digitised, image analysed and statistically evaluated to identify the presence and intensity of lobular fibrosis, its relation to age, clinical diagnoses of systemic autoimmune disease and the presence of rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP), antinuclear antibodies (ANAs), and anti-dsDNA serum markers. Significant correlation was found between lobular fibrosis and the presence of autoimmune disease (p = 0.023), mainly seropositive rheumatoid arthritis (p < 0.001). Also significant association was found between the fibrosis and the presence of serum anti-CCP (p < 0.001) and IgA/IgG/IgM-RF (p < 0.001, p < 0.001 and p = 0.008, respectively). Significant association was explored between the anti-dsDNA positivity and the negative histology groups (p = 0.033) and between the ANA positivity and the inflammation only group (p = 0.021). The results suggest that lobular fibrosis tends to associate to certain systemic autoimmune diseases, mainly seropositive rheumatoid arthritis, and seems to be rare in labial salivary gland biopsies of autoimmune diseases characterised by presence of anti-dsDNA. The close correlation of ANA positivity and the inflammation only histology was not surprising, since the majority of patients (62%) have Sjögren's syndrome, known for its inflammatory infiltrate. These findings emphasise that evaluation of lobular fibrosis and inflammation in histological samples of labial salivary gland biopsies are equally important. Copyright © 2018 Royal College of Pathologists of Australasia. Published by Elsevier B.V. All rights reserved.

Prevalence and clinical significance of nonorgan specific antibodies in patients with autoimmune thyroiditis as predictor markers for rheumatic diseases.

PubMed

Elnady, Basant M; Kamal, Naglaa M; Shaker, Raneyah H M; Soliman, Amal F; Hasan, Waleed A; Alghamdi, Hamed A; Algethami, Mohammed M; Jajah, Mohamed Bilal

2016-09-01

Autoimmune diseases are considered the 3rd leading cause of morbidity and mortality in the industrialized countries. Autoimmune thyroid diseases (ATDs) are associated with high prevalence of nonorgan-specific autoantibodies, such as antinuclear antibodies (ANA), antidouble-stranded deoxyribonucleic acid (anti-dsDNA), antiextractable-nuclear antigens (anti-ENAs), rheumatoid factor (RF), and anticyclic-citrullinated peptides (anti-CCP) whose clinical significance is unknown.We aimed to assess the prevalence of various nonorgan-specific autoantibodies in patients with ATD, and to investigate the possible association between these autoantibodies and occurrence of rheumatic diseases and, if these autoantibodies could be considered as predictor markers for autoimmune rheumatic diseases in the future.This study had 2 phases: phase 1; in which 61 ATD patients free from rheumatic manifestations were assessed for the presence of these nonorgan-specific autoantibodies against healthy 61 control group, followed by 2nd phase longitudinal clinical follow-up in which cases are monitored systematically to establish occurrence and progression of any rheumatic disease in association to these autoantibodies with its influences and prognosis.Regarding ATD patients, ANA, anti-dsDNA, Anti-ENA, and RF were present in a percentage of (50.8%), (18%), (21.3%), and (34.4%), respectively, with statistically significance difference (P < 0.5) rather than controls. Nearly one third of the studied group (32.8%) developed the rheumatic diseases, over 2 years follow-up. It was obvious that those with positive anti-dsDNA had higher risk (2.45 times) to develop rheumatic diseases than those without. There was a statistically significant positive linear relationship between occurrence of disease in months and (age, anti-dsDNA, anti-CCP, RF, and duration of thyroiditis). Anti-dsDNA and RF are the most significant predictors (P < 0.0001).ATD is more associated with rheumatic diseases than previously thought. Anti-dsDNA, RF, and anti-CCP antibodies may be used as predictive screening markers of systemic lupus erythematosus and RA, with early referral to rheumatologists for close follow-up and early diagnoses for appropriate disease management of the disease, as early disease control will allow better quality of life.

Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

PubMed Central

Didier, Kevin; Bolko, Loïs; Giusti, Delphine; Toquet, Segolene; Robbins, Ailsa; Antonicelli, Frank; Servettaz, Amelie

2018-01-01

Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren’s syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient’s management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs. PMID:29632529

Type B insulin-resistance syndrome presenting as autoimmune hypoglycemia, associated with systemic lupus erythematosus and interstitial lung disease.

PubMed

Kang, Seon Mee; Jin, Heung Yong; Lee, Kyung Ae; Park, Ji Hyun; Baek, Hong Sun; Park, Tae Sun

2013-01-01

We describe an unusual case of systemic lupus erythematosus with pulmonary manifestations presenting as hypoglycemia due to anti-insulin receptor antibodies. A 38-year-old female suffered an episode of unconsciousness and was admitted to hospital where her blood glucose was found to be 18 mg/dL. During the hypoglycemic episode, her serum insulin level was inappropriately high (2,207.1 pmol/L; normal range, 18 to 173) and C-peptide level was elevated (1.7 nmol/L; normal range, 0.37 to 1.47). Further blood tests revealed the presence of antinuclear antibodies, anti-double-stranded DNA antibodies, and anti-Ro/SSA, anti-La/SSB, anti-ribonucleoprotein, and anti-insulin receptor antibodies. A computed tomography scan of the abdomen, aimed at tumor localization, such as an insulinoma, instead revealed ground-glass opacities in both lower lungs, and no abnormal finding in the abdomen. For a definitive diagnosis of the lung lesion, video-associated thoracoscopic surgery was performed and histopathological findings showed a pattern of fibrotic non-specific interstitial pneumonia.

Rare association of celiac disease with myasthenia gravis in a patient with other immune disorders: a case report.

PubMed

de Almeida Menezes, Marcela; Ribeiro Cabral, Vírginia Lúcia; Lorena, Sônia S; Nucci, Anamarli; Andrade Santana, Priscila; Queiroz Silva, Cecília

2016-09-01

Celiac disease is described in association with several autoimmune diseases, but rarely with myasthenia gravis. We describe the case of a 31-year-old white woman with celiac disease who presented manifestations related to a hyperactive immune system, including macroamylasemia, false-positive anti-HCV, positive antinuclear antibody, and Raynaud's phenomenon. The introduction of a gluten-free diet (GFD) resolved these features, but myasthenia gravis (MG) symptoms unexpectedly occurred on that occasion. The role of a GFD in the course of autoimmune diseases has been studied and improvement has been reported in many diseases. However, there is no consensus in the literature regarding the course of neurological disorders associated with celiac disease. In the present case, a GFD did not prevent the appearance of symptoms related to myasthenia gravis. There are few reports on the association of celiac disease with myasthenia gravis and therefore little is known about the course and time of onset of myasthenia in celiac patients. The present case increases the knowledge about this unusual autoimmune neurological disease associated with celiac disease.

[A case of Grave's disease with MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) therapy following interstitial pneumonitis].

PubMed

Saeki, T; Miyamura, S; Nakano, M; Arakawa, M

1997-03-01

A 68-year-old man who developed MPO-ANCA-associated glomerulonephritis during propylthiouracil (PTU) treatment is reported. In 1986, he was diagnosed as having interstitial pneumonitis. Although he tested positive for antinuclear antibody and rheumatoid factor, he had no symptoms and was followed up without therapy. Five years later, the diagnosis of Graves's disease was made after complaints of body weight loss, diplopia and exophthalmos. Tests showed positivity for anti-thyroid stimulating hormone (TSH) receptor antibody, antithyroidperoxidase antibody and antithyroglobulin antibody. He was treated with PTU and prednisolone for four years. In November 1995, hematuria and proteinuria developed, and renal function deteriorated rapidly. A renal biopsy revealed crescentic glomerulonephritis and the serum titer of MPO-ANCA was markedly elevated. He was treated with a high dose of prednisolone and cyclophosphamide. Although the serum creatinine level gradually decreased, irreversible renal dysfunction persisted. In this patient, the presence of various autoantibodies had been recognized for several years before MPO-ANCA-associated glomerulonephritis developed. Polyclonal B-cell activation and PTU treatment may have played a role in the pathogenesis of MPO-ANCA-associated glomerulonephritis.

[Occupational semicircular lipoatrophy associated with serum adipokine abnormalities].

PubMed

Reinoso-Barbero, Luis; Díaz-Garrido, Ramón; González-Gómez, María-Fernanda; Olarrea, José; Gómez-Gallego, Félix; Bandrés, Fernando

2015-10-21

The aim of this study was to examine the relationship between semicircular lipoatrophy (SL), inflammation marker (high sensibility C-reactive protein [hs-CRP]), adipokines (leptine, chemerine and vaspine) and autoimmune markers (rheumatoid factor [RF], C3 and C4 complement fractions, antinuclear antibodies [ANA], HLA DR3, and DR4). Chemerine is an adipokine, but also is an immunity marker. A case-control study was performed in May 2013; 21 cases were included. The closest healthy coworker to each case was used as a control. We calculated Kruskal-Wallis nonparametric test. We found statistical significance (P<.05) between SL and raised hs-CRP, raised leptine and low chemerine. i) There seems to be an underlying inflammatory component (raised hs-CRP) in SL; ii) adipokine alteration (raised leptine and low chemerine) supports the idea that adipocytic differentiation is affected in SL, and iii) we have not found any immune marker associated with SL, except chemerine itself, which could explain a possible association between SL and immunity. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

[A case of systemic lupus erythematosus complicated with psoriasis vulgaris].

PubMed

Shidara, Kumi; Soejima, Makoto; Shiseki, Mariko; Ohta, Syuji; Nishinarita, Makoto

2003-12-01

A 49-years-old female admitted to our hospital because of skin eruptions on the extremities in 1985. She had suffered from polyarthralgia, skin eruptions since 1983. Physical examinations revealed discoid lesion, central nervous system involvement, and polyarthritis. Laboratory tests revealed leukopenia, thrombocytopenia, and hypocomplementemia. Antinuclear antibody, ant-DNA antibody, LE test were positive. From these findings, she was diagnosed as systemic lupus erythematosus (SLE). She developed lupus peritonitis in 1990 and 1994, which was successfully treated by steroid pulse therapy. Since then, the activity of SLE was in good control under administration of prednisolone 10 mg/day. Chilblain lupus was seen from 1993, Raynaud's phenomenon from 1996, and she further developed subcutaneous induration on her chest, back and upper extremities in 1999. Skin biopsy findings were compatible with lupus panniculitis. In 2002, erythematous patches with scales were observed on her right hand and left knee, and these skin lesions were histologically diagnosed as psoriasis vulgaris. An autoimmune response similar to SLE is speculated in psoriasis. We describe a rare case of SLE with various skin lesions including psoriasis vulgaris.

Cutaneous lupus erythematosus of elbows: A distinct entity?

PubMed

Singh, Nidhi; Chandrashekar, Laxmisha; Kumar, Nava; Kar, Rakhee; Sylvia, Mary Theresa; Thappa, Devinder Mohan

2016-01-01

The elbow is not recognized as common site for cutaneous lupus erythematosus (CLE) lesions. Twelve cases of CLE over the elbows were evaluated for systemic involvement and Cutaneous Lupus Disease Area and Severity Index activity and damage scores and Systemic Lupus Erythematosus Disease Activity Index scoring was done. Histopathological examination of the affected skin was performed in doubtful cases. Most of the patients were women (10, 83.3%) with mean age of 28.75 years. Three patients had only elbow lesions and the remaining nine patients had CLE lesions at sites other than the elbows, of which five had elbow lesions preceding skin lesions elsewhere over the body and three patients were not aware of whether elbow lesions preceded or succeeded CLE lesions at other sites, and one patient had noticed malar rash 9 months prior to elbow lesions. All the patients antinuclear antibody positivity, systemic involvement, and fulfilled criteria for systemic lupus erythematosus. This peculiar localization of CLE to the elbows may be associated with a greater risk of systemic involvement and may be an predictor of flare of LE.

Emerging new pathways of pathogenesis and targets for treatment in systemic lupus erythematosus and Sjogren's syndrome.

PubMed

Perl, Andras

2009-09-01

Systemic lupus erythematosus (SLE) and Sjogren's syndrome are chronic inflammatory diseases characterized by the dysfunction of T cells, B cells, and dendritic cells and the production of antinuclear autoantibodies. Here, we evaluate newly discovered molecular and cellular targets for the treatment of SLE and Sjogren's syndrome. The mammalian target of rapamycin in T and B cells has been successfully targeted for treatment of SLE with rapamycin or sirolimus both in patients and animal models. Inhibition of oxidative stress, nitric oxide production, interferon alpha, toll-like receptors 7 and 9, histone deacetylase, spleen tyrosine kinase, proteasome function, lysosome function, endosome recycling, and the nuclear factor kappa B pathway showed efficacy in animal models of lupus. B-cell depletion and blockade of anti-DNA antibodies and T-B cell interaction have shown success in animal models, whereas human studies have so far failed to accomplish clinical endpoints, possibly due to inadequacies in study design. Discovery of novel genes and signaling pathways in lupus pathogenesis offers novel biomarker-targeted approaches for treatment of SLE and Sjogren's syndrome.

[Terbinafine : Drug-induced lupus erythematodes and triggering of psoriatic skin lesions].

PubMed

Mayser, P

2016-09-01

Based on the technical information that oral terbinafine must be used with caution in patients with pre-existing psoriasis or lupus erythematosus, the literature was summarized. Terbinafine belongs to the drugs able to induce subcutaneous lupus erythematosus (SCLE)-with a relatively high risk. The clinical picture of terbinafine-induced SCLE may be highly variable and can also include erythema exsudativum multiforme-like or bullous lesions. Thus, differentiation of terbinafine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis may be difficult. Therefore, terbinafine should be prescribed with caution in patients who show light sensitivity, arthralgias, positive antinuclear antibodies or have a history of SLE or SCLE. Case reports include wide-spread, but mostly nonlife-threatening courses, which did not require systemic therapy with steroids or antimalarials in every case. Terbinafine is also able to induce or to aggravate psoriasis. The latency period seems to be rather short (<4 weeks). Terbinafine therefore is not first choice if a systemic therapy with antimycotics is indicated in a patient with psoriasis or psoriatic diathesis. Azole derivatives according to the guidelines may be used as an alternative.

Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.

PubMed

Wilbe, Maria; Jokinen, Päivi; Truvé, Katarina; Seppala, Eija H; Karlsson, Elinor K; Biagi, Tara; Hughes, Angela; Bannasch, Danika; Andersson, Göran; Hansson-Hamlin, Helene; Lohi, Hannes; Lindblad-Toh, Kerstin

2010-03-01

The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.

[Seven cases of remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome].

PubMed

Takahashi, Kozo; Fujinaga, Hiroshi; Kobayashi, Motoo; Naito, Takero; Iida, Hiroyuki; Aoki, Shuichi

2002-11-01

Among the elderly patients with seronegative polyarthritis, McCarty et al. (1985) proposed a disease entity of "remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome", but only a few cases have been reported in Japan. Here we report 7 cases suspicious of RS3PE syndrome, 2 men and 5 women with an average age of 75.9 years, ranging from 67-82 years. Their common findings were (1) relatively acute onset, (2) polyarthritis, (3) pitting edema of the dorsum of both hands and both feet, and (4) negative rheumatoid factor and antinuclear antibody. McCarty et al. found that RS3 PE syndrome was more prevalent in men; however, in our experience, the opposite was observed. The clinical courses of all patients were good, and they were effectively treated either by small dosages of oral prednisolone, nonsteroidal antiinflammatory drugs, or Chinese herbal (Kampo) medicines. Since this syndrome might not be rare in Japan, it seems necessary to evaluate elderly patients with seronegative polyarthritis with pitting edema as RS3PE syndrome in their routine medical examinations.

RS3PE syndrome: a clinical and immunogenetical study.

PubMed

Queiro, Rubén

2004-03-01

This study analyses the clinical, radiological, evolutive, and immunogenetical characteristics of a series of patients diagnosed with remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Reviewed were the clinical charts and human leukocyte antigen (HLA) profiles of all patients treated at a single teaching hospital fulfilling the features of this syndrome according to the definition of McCarty. Twelve cases were detected in ten men and two women aged from 62 to 85 years. Rheumatoid factor was negative in all cases, and antinuclear antibodies (ANA) were positive in two. All patients achieved complete resolution of their condition within 1 year with glucocorticoid (GC) use. Two relapsed after remission but responded again to low doses of GC. Four patients showed clinical and electrodiagnostic studies consistent with carpal tunnel syndrome. No specific HLA association could be found in this report. To date, none of these patients has developed definite rheumatic diseases, infections, or malignant diseases. Although the real nature of the syndrome is still a matter of debate, at least in our context, RS3PE remains a definite condition with an excellent prognosis.

Comparison of desmoglein ELISA and indirect immunofluorescence using two substrates (monkey oesophagus and normal human skin) in the diagnosis of pemphigus.

PubMed

Ng, Patricia P L; Thng, Steven T G; Mohamed, Khatija; Tan, Suat Hoon

2005-11-01

A prospective study was performed to assess the usefulness of desmoglein enzyme-linked immunosorbent assay testing compared with indirect immunofluorescence in the diagnosis of new cases of pemphigus, as well as to compare the relative sensitivities of monkey oesophagus and normal human skin as substrates for indirect immunofluorescence. These tests were performed on the sera of 29 consecutive new cases of pemphigus diagnosed over a 2-year period based on clinical, histological and direct immunofluorescence findings. Desmoglein enzyme-linked immunosorbent assay was positive in all patients whereas indirect immunofluorescence was positive in only 25 of 29 patients. All four patients with negative indirect immunofluorescence had positive antinuclear antibodies or cytoplasmic fluorescence that could have masked the anti-intercellular antibodies. Desmoglein enzyme-linked immunosorbent assay appeared to reflect the disease activity better than indirect immunofluorescence in a few patients who had active disease of recent onset. Monkey oesophagus was found to be superior or equal to human skin as a substrate for indirect immunofluorescence in both pemphigus vulgaris and foliaceus.

Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report.

PubMed

Etxagibel, Aitziber; Julià, M Rosa; Brotons, Alvaro; Company, M Margarita; Dolz, Carlos

2008-01-28

Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis.

Fibromyalgia and chronic fatigue syndrome in children.

PubMed

Itoh, Yasuhiko; Shigemori, Tomoko; Igarashi, Tohru; Fukunaga, Yoshitaka

2012-04-01

Fibromyalgia (FM) is characterized by widespread persistent pain and the presence of multiple discrete tender points. Chronic fatigue syndrome (CFS) is a syndrome characterized by debilitating fatigue associated with a variable number of non-specific complaints. Because neither condition had necessarily been recognized in children until recently, those patients have been treated as having school refusal without being diagnosed as having either syndrome. There is a considerable overlap of clinical symptoms between these two syndromes. It is therefore controversial as to whether these syndromes have the same pathogenesis or not. The aim of the present study was to clarify the relationship between these syndromes in children. Fifteen patients with FM and 21 patients with CFS were investigated both clinically and immunologically. Immunological assessments included thorough analysis of autoantibodies using several techniques. Anti-nuclear antibody titers were higher and the prevalence of anti-Sa antibody was far more frequent in CFS patients than in FM patients. CFS and FM are different from each other at least in childhood, from an immunological aspect, although some patients could have both conditions. © 2011 The Authors. Pediatrics International © 2011 Japan Pediatric Society.

Presumed lupus erythematosus cells identified in bronchoalveolar lavage fluid from a Mexican Hairless dog.

PubMed

Black, Laura J; Hechler, Ashley C; Duffy, Maura E; Beatty, Sarah S K

2017-06-01

A neutered male Mexican Hairless dog was presented for generalized weight loss and weakness. Initial laboratory testing and diagnostic imaging revealed thrombocytopenia and an interstitial to miliary lung pattern affecting all lung fields. Mild joint effusion was found on physical examination affecting the stifle, tarsal, carpal, and elbow joints. Examination of synovial fluid demonstrated an inflammatory polyarthropathy in 3 joints. Cytocentrifuged and direct preparations of the bronchoalveolar lavage (BAL) fluid sample were made and cells consistent with lupus erythematosus (LE) cells and ragocytes were found. Based on these findings, the anti-nuclear antibody (ANA) titer was determined as 1:640. A clinical diagnosis of systemic LE was made based on the satisfaction of 2 major criteria (thrombocytopenia and inflammatory polyarthritis), 4 minor criteria (central nervous system signs, lymphadenopathy, fever of unknown origin, and pleuritis), positive ANA titer, and the identification of presumed LE cells in BAL fluid. This case report highlights a novel finding of LE cells in respiratory secretions and provides a review of diagnostic criteria of systemic LE. © 2017 American Society for Veterinary Clinical Pathology.

HEp-2 cell image classification method based on very deep convolutional networks with small datasets

NASA Astrophysics Data System (ADS)

Lu, Mengchi; Gao, Long; Guo, Xifeng; Liu, Qiang; Yin, Jianping

2017-07-01

Human Epithelial-2 (HEp-2) cell images staining patterns classification have been widely used to identify autoimmune diseases by the anti-Nuclear antibodies (ANA) test in the Indirect Immunofluorescence (IIF) protocol. Because manual test is time consuming, subjective and labor intensive, image-based Computer Aided Diagnosis (CAD) systems for HEp-2 cell classification are developing. However, methods proposed recently are mostly manual features extraction with low accuracy. Besides, the scale of available benchmark datasets is small, which does not exactly suitable for using deep learning methods. This issue will influence the accuracy of cell classification directly even after data augmentation. To address these issues, this paper presents a high accuracy automatic HEp-2 cell classification method with small datasets, by utilizing very deep convolutional networks (VGGNet). Specifically, the proposed method consists of three main phases, namely image preprocessing, feature extraction and classification. Moreover, an improved VGGNet is presented to address the challenges of small-scale datasets. Experimental results over two benchmark datasets demonstrate that the proposed method achieves superior performance in terms of accuracy compared with existing methods.

Subacute Noninfective Inflammatory Encephalopathy: Our Experience and Diagnostic Problems

PubMed Central

Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Sindhu, Dodmalur Malikarjuna; Pai, Anupama Ramakanth

2017-01-01

Introduction: Immune dysregulation associated encephalopathies present with significant psychiatric manifestations and only a few soft neurological and general systemic features. They are generally resistant to treatment with psychiatric medications. Generalized orthostatic myoclonus and faciobrachial dystonic seizures are mistaken as Creutzfeldt-Jakob disease and subacute sclerosing panencephalitis. Patients and Methods: Forty-two patients seen during 2010–2015 and diagnosed as noninfective encephalopathy were analyzed. Those patients with infective causes and those who had significant features of systemic manifestations of vasculitis and other disorders of central nervous system were excluded from the study. They were investigated with cerebrospinal fluid imaging, electroencephalogram (EEG), and antibody profile. Results: More than 70% patients had psychiatric manifestation as presenting features and reported to psychiatrist. Three patients had paraneoplastic and others N-methyl-D-aspartate, voltage-gated potassium channel, thyroid peroxidase, antinuclear antibody related, and few were due to unknown antibody. Conclusion: Serious diagnostic errors are common and early diagnosis is based on high degree suspicion in patients presenting with new-onset refractory psychosis. Soft neurological features should be looked for and EEG serves as a very sensitive tool in establishing organicity. PMID:28515556

The concordance of serial ANA tests in an Australian tertiary hospital pathology laboratory.

PubMed

Lee, Adrian Y S; Hudspeth, Andrew R; Adelstein, Stephen

2016-10-01

The antinuclear antibody (ANA) tests are some of the more frequently requested tests for the diagnosis of autoimmunity. Although they are used primarily as diagnostic blood tests, multiple requests on the same patient continue to be encountered in the laboratory. This retrospective analysis of serial ANA testing at one pathology laboratory in Australia is the first study that examines the statistical concordance and possible implications of this on clinical practice. High-titred ANA have quite good repeatability for titre and pattern, and low-titred ANA, which can be non-specific, have poor repeatability. Staining patterns are, in general, almost random in nature on serial tests when compared to the first-obtained ANA pattern for each patient. This study confirms that there is little benefit in serial ANA testing, and only if there is a clear change in the patient's clinical picture would repeat of an initial low-titred ANA be useful. The findings reinforce the need for pathology stewardship to minimise costs, wasted resources and unnecessary referrals. Copyright © 2016 Royal College of Pathologists of Australasia. All rights reserved.

Antitopoisomerase antibody positivity predates nailfold capillaroscopy abnormalities in scleroderma. Postulated classification of 'prescleroderma'.

PubMed

Englert, H; Champion, D; Wu, J C; Giallussi, J; McGrath, M; Manolios, N

2011-02-01

In a patient with early topoisomerase antibody-positive scleroderma, antinuclear antibody positivity was fortuitously observed to predate nailfold capillaroscopy changes. Using this case as a template, the prediagnostic phase of the presumed multifactorial disease may be divided into 5 temporal phases--phase 1 representing conception and intrauterine environment, phase 2 representing the extrauterine environment predating environmental exposure; phase 3 representing the early post-environmental exposure interval with no detectable perturbed body status; phase 4 representing the post-environmental exposure interval characterized by autoantibody production and microvascular changes, and phase 5, the symptomatic clinical prediagnostic interval (Raynaud's, skin, musculoskeletal, gastrointestinal, cardiorespiratory) prompting scleroderma diagnosis. Temporal classification of prescleroderma aids in both the understanding and definition of scleroderma 'onset'. If altered nailfold capillaries and autoantibodies develop at comparable rates, and if the findings from this case--that autoantibody changes precede microvascular changes--are truly representative of the preclinical disease phase, then these findings argue that the evolution of the disease is from within the vessel outwards, rather than vice versa. © 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.

NZB/NZW F1 mouse nephritis and immune response are not changed by treatment with a 15-lipoxygenase derivative.

PubMed

Aldigier, J C; Cook, J; Delebassée, S; Guibert, F; Touchard, G; Juzan, M; Gualde, N

1992-10-01

15-HETE is an arachidonic acid derivative issued from the 15 lipoxygenase pathway. This fatty acid possesses immunomodulatory capabilities since it was reported that it generates CD8 + suppressor T-cells either in vitro or ex vivo. The aim of the present report was to study if the suppressive capabilities of 15-HETE were able to influence the onset of the NZB/NZW Fl auto-immune disease. For that purpose we produced 15-HETE and injected the eicosanoid twice a week to NZB/WFI mice for 40 weeks. During the 15-HETE treatment of the animals it was observed an augmentation of the proliferative response of lectin-stimulated splenocytes (at weeks 20 and 30) then the thymidine uptake decreased (at week 40). In fact we observed that among 15-HETE treated mice the evolution of the nephropathy was not changed, the 'glomerular activity score' remained the same for the treated animals compared to controls. On the contrary antinuclear antibodies occurred earlier even if in some experiments the generation of CD8 + cells was demonstrated.

Selective Memory to Apoptotic Cell-Derived Self-Antigens with Implications for Systemic Lupus Erythematosus Development.

PubMed

Duhlin, Amanda; Chen, Yunying; Wermeling, Fredrik; Sedimbi, Saikiran K; Lindh, Emma; Shinde, Rahul; Halaby, Marie Jo; Kaiser, Ylva; Winqvist, Ola; McGaha, Tracy L; Karlsson, Mikael C I

2016-10-01

Autoimmune diseases are characterized by pathogenic immune responses to self-antigens. In systemic lupus erythematosus (SLE), many self-antigens are found in apoptotic cells (ACs), and defects in removal of ACs from the body are linked to a risk for developing SLE. This includes pathological memory that gives rise to disease flares. In this study, we investigated how memory to AC-derived self-antigens develops and the contribution of self-memory to the development of lupus-related pathology. Multiple injections of ACs without adjuvant into wild-type mice induce a transient primary autoimmune response without apparent anti-nuclear Ab reactivity or kidney pathology. Interestingly, as the transient Ab response reached baseline, a single boost injection fully recalled the immune response to ACs, and this memory response was furthermore transferable into naive mice. Additionally, the memory response contains elements of pathogenicity, accompanied by selective memory to selective Ags. Thus, we provide evidence for a selective self-memory that underlies progression of the response to self-antigens with implications for SLE development therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

Accelerated recovery from nephrotic syndrome with acute renal failure by double filtration plasmapheresis in a patient with lupus podocytopathy.

PubMed

Iwazu, Yoshitaka; Akimoto, Tetsu; Izawa, Sayoko; Inoue, Makoto; Muto, Shigeaki; Ando, Yasuhiro; Iwazu, Kana; Fukushima, Noriyoshi; Yumura, Wako; Kusano, Eiji

2012-06-01

We describe a case of an adult female who presented with nephrotic syndrome. She was diagnosed with systemic lupus erythematosus with serum antinuclear antibodies, leucopenia with lymphopenia, butterfly erythema, and nephrotic syndrome. Renal biopsy revealed normal glomeruli with diffuse effacement of the foot processes, consistent with lupus podocytopathy. Although human albumin replacement was performed initially, acute renal failure developed rapidly. Therefore, she was treated with double filtration plasmapheresis (DFPP) in addition to oral steroid. After steroid therapy combined with DFPP, the renal function and proteinuria improved rapidly. Although the impact of DFPP on the treatment of lupus nephritis remains to be delineated, our observations suggest that DFPP in lupus podocytopathy played a pivotal role in facilitating the early recovery from renal injuries. Because of the rapid improvement of renal function without any change in body weight by DFPP, acute renal failure in the setting of lupus podocytopathy might contribute to an alternative pathophysiological factor for the diminished glomerular filtration rate, similar to that observed in the setting of idiopathic minimal change glomerulopathy.

Churches and nuclear deterrence

DOE Office of Scientific and Technical Information (OSTI.GOV)

van Voorst, L.B.

In contrast to a history of support for our nation's involvement in wars, US churches are now in the process of edging toward a direct confrontation with the Reagan Administration over nuclear weapons and deterrence policy. This new attitude is attributed to two main factors: the growing awareness of the end of American strategic superiority and the concern over the Reagan Administration's attitude toward strategic nuclear issues. This newly widespread determination among the churches to challenge public policy on nuclear issues is addressed by examining the various churches and their efforts in the anti-nuclear movement. The Catholic Bishops' Draft Pastoralmore » Letter is discussed at length and is considered to be the most radical effort by any American church to define moral standards for the nuclear era. In contrast, the historical Protestant treatment differs considerably from the Catholic initiative; it started earlier but has been more fragmented and disparate. Only the American Jewish community as a whole has been, with a few notable exceptions, reluctant to become involved in the movement. The ultimate political question raised is how this religious involvement will influence American strategic nuclear doctrines. 27 references.« less

Treatment of juvenile idiopathic arthritis-associated uveitis: challenges and update.

PubMed

Rabinovich, C Egla

2011-09-01

To update the current understanding of the risk factors for poor outcomes in juvenile idiopathic arthritis-related uveitis. In addition, current therapies, both traditional and biological, are reviewed. Male sex, independent of age or antinuclear antibody status, is associated with increased ocular morbidity. Having anterior chamber inflammation on first exam increases the risk of developing vision-threatening eye complications. Presence of one complication increases the risk of developing another. Risk of cataract development associated with topical glucocorticoid use is better defined. Longer duration of remission on therapy has been found to decrease the risk of disease flare after discontinuation of methotrexate. Recent studies of both nonbiological and biological therapies for arthritis-related uveitis are discussed. With a better understanding of risk factors associated with the ocular morbidity of uveitis associated with juvenile idiopathic arthritis, aggressive therapies can be targeted for improved visual outcomes. Alternative treatments to avoid long-term corticosteroid use include the use of antimetabolites and biological therapies. More prospective comparator studies and/or use of multicenter databases are needed to better understand best treatments.

An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-Nup syndrome.

PubMed

Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J; Targoff, Ira N; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

2014-11-01

Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n = 112), mixed connective tissue disease (n = 35), systemic lupus (n = 94), rheumatoid arthritis (n = 45), or other rheumatic diseases (n = 107), nor was it observed in 62 normal adults.Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n = 2 patients), Nup90 (n = 1), Nup62 (n = 1), and gp210 (n = 1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1*0501 allele associated with an increased risk for autoimmune myositis.In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an "anti-nup syndrome."

[Expression and Clinical Significance of Semaphorin 3A in serum and mononuclear cells in patients with systemic lupus erythematosus].

PubMed

Gao, H; Ma, X X; Guo, Q; Zou, Y D; Zhong, Y C; Xie, L F; Shao, M; Zhang, X W

2017-02-07

Objective: To determine the expression of Sema3A in serum and peripheral blood mononuclear cells (PBMC) of patients with systemic lupus erythematosus (SLE), to analysis the correlation of Sema3A expression and SLE clinical manifestations and laboratory indexes, and to evaluate the diagnostic value of Sema3A in patients with SLE. Methods: The concentration of serum Sema3A was detected by enzyme-linked immuno sorbent assay (ELISA) in patients with SLE, healthy controls (HC) and diseases controls. In addition, the mRNA expression level of Sema3A was examined in PBMC by real-time polymerase chain reaction. The correlation of serum Sema3A level and clinical and laboratory features of SLE patients were analyzed. Unpaired t test, Kruskal-Wallis test, Mann-Whitney U test, χ(2) test, Pearson and Spearman correlation analysis were used to statistical analysis by using SPSS 13.0. Results: (1) Serum Sema3A concentration in patients with SLE was significantly lower than that in HC groups ( P <0.01). (2) Consistent with the serum level, the Sema3A mRNA level in SLE was lower than that in HC ( P =0.001). And the mRNA expression of Nrp-1 in SLE was also lower than that in HC ( P <0.01). (3) The serum Sema3A level in patients with SLE was positively correlated with haemoglobin (HGB) ( r =0.271, P <0.013), platelet (PLT) ( r =0.600, P <0.011), complement 3 (C3) ( r =0.234, P =0.0027) and complement 4 (C4) ( r =0.159, P =0.434) levels. Whereas, the expression of Sema3A was negatively correlated with SLE disease activity index (SLEDAI) ( r =-0.286, P =0.036). (4) Area under curve illustrated by ROC curve was 0.876 (95% CI: 0.846-0.906). The best cut-off value for the diagnosis of SLE was 6.31 μg/L, with the sensitivity of 80.6% and the specificity of 77.5%. The Youden index was 0.581. Above results indicated good validity of Sema3A as a diagnostic marker for SLE. (5) The HGB, PLT, C3 and C4 levels in the group of Sema3A- positiveSLE patients (≤6.31 μg/L) were lower than that in negative group (>6.31 μg/L), while CRP level and SLEDAI of positive group was higher than that in negative group( P <0.05). In addition, the positive rate of antinuclear antibodies ( P =0.046) and anticardiolipin antibody ( P =0.018) in the Sema3A-negative group were also significantly higher than that of negative group. Conclusions: Sema3A and Nrp-1 was both decreased in serum and PBMC of SLE patients, suggesting that the circulating expression of Sema3A and Nrp-1 was seriously defected in SLE. Circulating Sema3A was significantly correlated with disease activity and blood damage in patients with SLE. The result of ROC curve showed that Sema3A had the potential to be a new diagnostic biomarker in SLE.

Repeated administration of dapirolizumab pegol in a randomised phase I study is well tolerated and accompanied by improvements in several composite measures of systemic lupus erythematosus disease activity and changes in whole blood transcriptomic profiles.

PubMed

Chamberlain, Chris; Colman, Peter J; Ranger, Ann M; Burkly, Linda C; Johnston, Geoffrey I; Otoul, Christian; Stach, Christian; Zamacona, Miren; Dörner, Thomas; Urowitz, Murray; Hiepe, Falk

2017-11-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease associated with diffuse immune cell dysfunction. CD40-CD40 ligand (CD40L) interaction activates B cells, antigen-presenting cells and platelets. CD40L blockade might provide an innovative treatment for systemic autoimmune disorders. We investigated the safety and clinical activity of dapirolizumab pegol, a polyethylene glycol conjugated anti-CD40L Fab' fragment, in patients with SLE. This 32-week randomised, double-blind, multicentre study (NCT01764594) evaluated repeated intravenous administration of dapirolizumab pegol in patients with SLE who were positive for/had history of antidouble stranded DNA/antinuclear antibodies and were on stable doses of immunomodulatory therapies (if applicable). Sixteen patients were randomised to 30 mg/kg dapirolizumab pegol followed by 15 mg/kg every 2 weeks for 10 weeks; eight patients received a matched placebo regimen. Randomisation was stratified by evidence of antiphospholipid antibodies. Patients were followed for 18 weeks after the final dose. No serious treatment-emergent adverse events, thromboembolic events or deaths occurred. Adverse events were mild or moderate, transient and resolved without intervention. One patient withdrew due to infection.Efficacy assessments were conducted only in patients with high disease activity at baseline. Five of 11 (46%) dapirolizumab pegol-treated patients achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment response (vs 1/7; 14% placebo) and 5/12 (42%) evaluable for SLE Responder Index-4 responded by week 12 (vs 1/7; 14% placebo). Mechanism-related gene expression changes were observed in blood RNA samples. Dapirolizumab pegol could be an effective biological treatment for SLE. Further studies are required to address efficacy and safety. NCT01764594. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Autoimmune paediatric liver disease

PubMed Central

Mieli-Vergani, Giorgina; Vergani, Diego

2008-01-01

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy. PMID:18528933

Autoimmune paediatric liver disease.

PubMed

Mieli-Vergani, Giorgina; Vergani, Diego

2008-06-07

Liver disorders with a likely autoimmune pathogenesis in childhood include autoimmune hepatitis (AIH), autoimmune sclerosing cholangitis (ASC), and de novo AIH after liver transplantation. AIH is divided into two subtypes according to seropositivity for smooth muscle and/or antinuclear antibody (SMA/ANA, type 1) or liver kidney microsomal antibody (LKM1, type 2). There is a female predominance in both. LKM1 positive patients tend to present more acutely, at a younger age, and commonly have partial IgA deficiency, while duration of symptoms before diagnosis, clinical signs, family history of autoimmunity, presence of associated autoimmune disorders, response to treatment, and long-term prognosis are similar in both groups. The most common type of paediatric sclerosing cholangitis is ASC. The clinical, biochemical, immunological, and histological presentation of ASC is often indistinguishable from that of AIH type 1. In both, there are high IgG, non-organ specific autoantibodies, and interface hepatitis. Diagnosis is made by cholangiography. Children with ASC respond to immunosuppression satisfactorily and similarly to AIH in respect to remission and relapse rates, times to normalization of biochemical parameters, and decreased inflammatory activity on follow up liver biopsies. However, the cholangiopathy can progress. There may be evolution from AIH to ASC over the years, despite treatment. De novo AIH after liver transplantation affects patients not transplanted for autoimmune disorders and is strikingly reminiscent of classical AIH, including elevated titres of serum antibodies, hypergammaglobulinaemia, and histological findings of interface hepatitis, bridging fibrosis, and collapse. Like classical AIH, it responds to treatment with prednisolone and azathioprine. De novo AIH post liver transplantation may derive from interference by calcineurin inhibitors with the intrathymic physiological mechanisms of T-cell maturation and selection. Whether this condition is a distinct entity or a form of atypical rejection in individuals susceptible to the development of autoimmune phenomena is unclear. Whatever its etiology, the recognition of this potentially life-threatening syndrome is important since its management differs from that of standard anti-rejection therapy.

Pathophysiology of HIV related thrombocytopenia: an analysis of 41 patients.

PubMed Central

Domínguez, A; Gamallo, G; Garcia, R; Lopez-Pastor, A; Peña, J M; Vazquez, J J

1994-01-01

AIM--To analyse the pathogenic mechanism of HIV related thrombocytopenia. METHODS--Forty one patients with thrombocytopenia and HIV-1 infection were investigated over two years. Anticardiolipin antibodies were measured using an enzyme linked immunosorbent assay and antiplatelet antibodies were measured using an immunocapture technique. Tests for VDRL, C3 and C4, antinuclear antibodies and rheumatoid factor were also carried out in all patients and 80 control subjects (HIV-1 positive but non-thrombocytopenic). Indiumoxine labelled platelets were transfused in 13 patients. P24 antigen were also measured in 12 bone marrow aspirates. RESULTS--Antiplatelet antibodies and circulating immune complexes were found exclusively in the thrombocytopenic group; values for antiplatelet antibodies and circulating immune complexes were both higher in homosexual and bisexual patients. Three kinds of pattern were observed using 111 In-labelled platelets: splenic (n = 10); hepatic (n = 2); and destruction of bone marrow in just one case. The two most influential factors in the sequestration pattern were antiplatelet antibodies in the splenic uptake and circulating immune complexes in the hepatic and marrow sequestration. All patients, except three, had decreased platelet recovery. In those patients with a CD4 lymphocyte count of less than 200 x 10(6) cells/l the recovery was clearly greater (53%) than in patients who had more than 200 x 10(6) /l (28%). Finally, in seven of the 12 patients who were chosen for immunohistochemical study, p24 antigen was detected in the megakaryocytes, verifying that HIV-1 infects such cells. CONCLUSIONS--The pathogenic mechanism of HIV related thrombocytopenia is probably multifaceted. Antiplatelet antibodies and circulating immune complexes would cause peripheral destruction in the spleen, liver, and bone marrow, in that order; and, on the other hand, there would be an ineffective immune thrombopoiesis and direct infection of the megakaryocytes which could cause a change in the function and maturity of these cells. PMID:7829697

Serum Biomarkers for Discrimination between Hepatitis C-Related Arthropathy and Early Rheumatoid Arthritis.

PubMed

Siloşi, Isabela; Boldeanu, Lidia; Biciuşcă, Viorel; Bogdan, Maria; Avramescu, Carmen; Taisescu, Citto; Padureanu, Vlad; Boldeanu, Mihail Virgil; Dricu, Anica; Siloşi, Cristian Adrian

2017-06-19

In the present study, we aimed to estimate the concentrations of cytokines (interleukin 6, IL-6, tumor necrosis factor-α, TNF-α) and auto-antibodies (rheumatoid factor IgM isotype, IgM-RF, antinuclear auto-antibodies, ANA, anti-cyclic citrullinated peptide antibodies IgG isotype, IgG anti-CCP3.1, anti-cardiolipin IgG isotype, IgG anti-aCL) in serum of patients with eRA (early rheumatoid arthritis) and HCVrA (hepatitis C virus-related arthropathy) and to assess the utility of IL-6, TNF-α together with IgG anti-CCP and IgM-RF in distinguishing between patients with true eRA and HCVrA, in the idea of using them as differential immunomarkers. Serum samples were collected from 54 patients (30 diagnosed with eRA-subgroup 1 and 24 with HCVrA-subgroup 2) and from 28 healthy control persons. For the evaluation of serum concentrations of studied cytokines and auto-antibodies, we used immunoenzimatique techniques. The serum concentrations of both proinflammatory cytokines were statistically significantly higher in patients of subgroup 1 and subgroup 2, compared to the control group ( p < 0.0001). Our study showed statistically significant differences of the mean concentrations only for ANA and IgG anti-CCP between subgroup 1 and subgroup 2. We also observed that IL-6 and TNF-α better correlated with auto-antibodies in subgroup 1 than in subgroup 2. In both subgroups of patients, ROC curves indicated that IL-6 and TNF-α have a higher diagnostic utility as markers of disease. In conclusion, we can say that, due to high sensitivity for diagnostic accuracy, determination of serum concentrations of IL-6 and TNF-α, possibly in combination with auto-antibodies, could be useful in the diagnosis and distinguishing between patients with true eRA and HCV patients with articular manifestation and may prove useful in the monitoring of the disease course.

Juvenile systemic lupus erythematosus in Nigeria.

PubMed

Adelowo, O O; Olaosebikan, B H; Animashaun, B A; Akintayo, R O

2017-03-01

Juvenile systemic lupus erythematosus (JSLE) is a complex multisystemic autoimmune disorder of unknown cause. It accounts for about one in five cases of SLE. The tendency for SLE to run a fulminant course when it starts in childhood has made JSLE a potentially more severe disease than adult SLE. Reports of JSLE from sub-Saharan Africa are scanty in spite of the increasing reports of adult SLE. We conducted a 4-year retrospective study of JSLE cases seen at the Lagos State University Teaching Hospital between January 2010 and December 2014. Out of the 12 patients studied, eight were girls and four were boys. All patients had positive antinuclear antibody and extractable nuclear antibody tests. Anti-dsDNA antibody was positive in 10 patients. Eight patients had renal disease while four patients had neuropsychiatric manifestations. Haematological abnormalities and constitutional symptoms were present in all patients. Patients were treated with pulse methylprednisolone, oral prednisolone, hydroxychloroquine and azathioprine. Three patients also received rituximab. In conclusion, JSLE exists in Nigeria and exhibits clinical and immunological characteristics similar to its pattern in other parts of the world. It is, however, diagnosed late and is possibly being underdiagnosed as there is no paediatric rheumatologist in the country.

Lupus Panniculitis as an Initial Manifestation of Systemic Lupus Erythematosus: A Case Report.

PubMed

Zhao, Yu-Kun; Wang, Fang; Chen, Wen-Na; Xu, Rui; Wang, Zhuo; Jiang, Yuan-Wen; Luo, Di-Qing; Han, Jian-De

2016-04-01

Lupus erythematosus panniculitis (LEP) is a variant of chronic cutaneous lupus erythematosus (CCLE). Reported cases of LEP lesions before the diagnosis of systemic lupus erythematosus (SLE) were very rare; only 9 cases have been reported, to the best of our knowledge. We now describe the case of a 19-year-old male patient, with an overall review of the English literature. In the earliest stage of the present case, nodules and ulcers involved his left leg and face, with no other accompanied symptoms. The skin lesions disappeared after treatment with methylprednisolone, 16 mg/d for 1 month. Seven months after discontinuing methylprednisolone, the cutaneous nodules and ulcers on his back recurred and were accompanied by fever, hair loss, and polyarthritis. Blood tests revealed leucopenia, positive antinuclear antibody and Smith antibody, and proteinuria. Histopathological findings were most consistent with LEP. This was followed sequentially by the diagnosis of SLE. The patient improved again after treatment with methylprednisolone and cyclophosphamide.Patients with LEP should have regular follow-ups because the development of SLE is possible. Early diagnosis and proper treatment is pivotal to improve the prognosis of such patients.

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody.

PubMed

Barnett, M; Prosser, J; Sutton, I; Halmagyi, G M; Davies, L; Harper, C; Dalmau, J

2001-02-01

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

Nuclear obligations: Nuremberg law, nuclear weapons, and protest

DOE Office of Scientific and Technical Information (OSTI.GOV)

Burroughs, J.R.

1991-01-01

Nuclear weapons use and deployment and nonviolent anti-nuclear protests are evaluated. Use of nuclear weapons would constitute war crimes and crimes against humanity as defined in both the Nuremberg Charter and Allied Control Council Law No. 10 and applied by the International Military Tribunal and other Nuremberg courts. Strategic and atomic bombing during World War 2 did not set a precedent for use of nuclear weapons. The consequentialist argument for World War 2 bombing fails and the bombing has also been repudiated by codification of the law of war in Protocol 1 to the 1949 Geneva Conventions. The legality ofmore » deploying nuclear weapons as instruments of geopolitical policy is questionable when measured against the Nuremberg proscription of planning and preparation of aggressive war, war crimes, and crimes against humanity and the United Nations Charter's proscription of aggressive threat of force. While states' practice of deploying the weapons and the arms-control treaties that regulate but do not prohibit mere possession provide some support for legality, those treaties recognize the imperative of preventing nuclear war, and the Nuclear Non-Proliferation Treaty commits nuclear-armed states to good-faith negotiation of nuclear disarmament.« less

Very delayed lupus nephritis: a report of three cases and literature review.

PubMed

Alexandre, André R; Carreira, Pedro L; Isenberg, David A

2018-01-01

Lupus nephritis (LN) affects up to 50% of patients with Systemic Lupus Erythematosus (SLE) and is associated with a worse prognosis. LN usually develops within the first 5 years of the onset of the disease. We report three patients with very delayed LN (DLN) diagnosed after 15 or more years after SLE diagnosis. The three patients were non-Caucasian women with adolescent or adult-onset SLE. Each had antinuclear, anti-dsDNA and anti-Ro antibodies. Hydroxychloroquine was prescribed for each. Their disease courses were characterised by sporadic non-renal flares controlled by steroids and, in two cases, by one cycle of rituximab. Unexpectedly, they developed proteinuria, haematuria and lowering of estimated glomerular filtration rate with clinical signs of renal disease. LN was confirmed by renal biopsy. Reviewing them, each showed serological signs of increasing disease activity (rising levels of anti-dsDNA antibodies and fall in C3) that predated clinical or laboratory signs of LN by 1-3 years. Reviewing the literature, we found a lack of knowledge about DLN starting more than 15 years after SLE diagnosis. With the increasing life expectancy of patients with SLE it is likely that more cases of very DLN will emerge.

Autoantibodies and human immunodeficiency viruses infection: a case-control study.

PubMed

Chretien, P; Monier, J C; Oksman, F; San Marco, M; Escande, A; Goetz, J; Cohen, J; Baquey, A; Humbel, R L; Sibilia, J

2003-01-01

To determine the prevalence of organ-specific and non-specific autoantibodies in HIV-infected patients. A multicentric collaborative case-control study including 105 HIV patients and 100 sex- and age-matched HIV-negative healthy volunteers. Antinuclear, anti-ds DNA, anti-histone, anti-Sm, rheumatoid factor(IgM), anti-beta 2 glycoprotein 1, antineutrophil cytoplasmic, anti-LKM1, anti-LCA1, anti-gastric parietal cell, antiplatelet, anti-intermediate filament, anti-mitotic spindle apparatus, anti-Golgi, anti-ribosome and anti-thyroid autoantibodies were screened in six European laboratories. Only IgG and IgM anticardiolipin, IgG antiplatelet, anti-smooth muscle and anti-thyroglobulin antibodies were statistically more frequent in HIV patients. There was no correlation with the numbers of CD4+ cells except in the case of anti-smooth muscle antibodies. We were unable to find specific autoantibodies such as anti-ds DNA, anti-Sm, AMA, anti-LKM1, anti-LCA1 or anti-beta 2 GP1 antibodies in these patients. Our results indicate that the autoantibody profile of HIV infections is comparable to those of other chronic viral infections. HIV does not seem to be more autoimmunogenic than other viruses.

[A case of lupus myocarditis and nephritis with transient foramen jugular syndrome].

PubMed

Kohro-Kawata, J; Nakamura, H; Yamamoto, T; Fukuta, S; Matsuzaki, M

1997-10-01

A 46-year-old man was admitted to our clinic because of acute heart failure. Six years before admission he was pointed out cardiomegary and hematuria. One year later, he was diagnosed as having jugular foramen syndrome. On admission, he had a fever and dyspnea. Pansystolic blowing murmur was audible at the apex. The chest ratio on his chest X-ray was 52.5%. An electrocardiogram showed left ventricular hypertrophy. An echocardiogram showed marked dilatation and severe dysfunction of left ventricle. Radionuclide scanning with technetium 99 m pyrophosphate identified inflammatory change in the apex. Myocardial biopsy showed fibrotic degeneration and IgG deposits in myocardium. Blood examination showed anemia, lymphopenia. positive anti-nuclear antibody (1000 times, shaggy pattern), positive anti ds-DNA antibody and hypocomplementemia. Furthermore, proteinuria was pointed out. Renal biopsy showed focal segmental glomerulonephritis with active necrotizing lesion (type III nephritis). Lupus myocarditis and nephritis was diagnosed. After prednisolone (80 mg/day) was administered. left ventricular function and hypocomplementemia improved. The ACE inhibitor was also used for proteinuria. In spite of a little amount of blood transfusion, he showed hepatic hemosiderosis. We suspect that the cause of hemosiderosis was related chronic inflammation of active lupus. It was treated with Erythropoietin.

Primary sclerosing cholangitis

PubMed Central

Silveira, Marina G; Lindor, Keith D

2008-01-01

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by inflammation and fibrosis of the bile ducts, resulting in end-stage liver disease and reduced life expectancy. PSC primarily affects young and middle-aged men, often in association with underlying inflammatory bowel disease. The etiology of PSC includes immune-mediated components and elements of undefined nature. A cholestatic picture of liver biochemistries with elevations in serum alkaline phosphatase, nonspecific autoantibodies such as perinuclear antineutrophilic antibody, antinuclear antibodies and smooth muscle antibodies, and diffuse multifocal biliary strictures, resulting in a ‘beaded’ appearance on radiographic studies, are the hallmarks of the disease. No effective medical therapy is currently available, although clinical studies are in progress. Ursodeoxycholic acid at high doses (28 mg/kg/day to 30 mg/kg/day) is the most promising agent but is unproven so far. Liver transplantation is currently the only life-extending therapy for patients with end-stage disease, although recurrent disease can be observed in the transplanted liver. The multiple complications of PSC include pruritus, fatigue, vitamin deficiencies, metabolic bone disease, peristomal varices, bacterial cholangitis, dominant biliary strictures, gallbladder stones and polyps, and malignancy, particularly cholangiocarcinoma, which is the most lethal complication of PSC. PMID:18701947

Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody

PubMed Central

Barnett, M; Prosser, J; Sutton, I; Halmagyi, G; Davies, L; Harper, C; Dalmau, J

2001-01-01

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

 PMID:11160472

Detection of lupus erythematosus cells in pleural effusion: An unusual presentation of systemic lupus erythematosus.

PubMed

Gulhane, Sushma; Gangane, Nitin

2012-01-01

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease typically diagnosed by a combination of physical findings and clinical laboratory testing. Several decades ago, the diagnosis of lupus included the lupus erythematosus (LE) cell assay. SLE is associated with pleuropulmonary manifestations in well over 50% of cases. Although pleural effusion is common but very rarely is the initial manifestation of disease. There are very few reports of SLE diagnosed in a cytopathology laboratory. We report an unusual case of SLE in a 16-year-old female who presented with acute shortness of breath, fever and cough. Her chest radiograph showed bilateral pleural effusion. This effusion was tapped and sent to the cytopathology laboratory. The cytological examination of the pleural fluid revealed numerous LE cells and led to the diagnosis of SLE. Autoimmune serology techniques such as anti-nuclear antibody staining have replaced the LE cell assay. However, as presented in this report and found in a review of the literature, the in vivo finding of LE cells by cytopathology can provide an important clue to the diagnosis of SLE, especially when associated with an uncommon presentation.

Raynaud’s phenomenon - assessment and differential diagnoses.

PubMed

Linnemann, Birgit; Erbe, Matthias

2015-05-01

Raynaud’s phenomenon (RP) is characterised by paroxysmal reversible episodes of vasospasm, usually involving peripheral small vessels of the fingers or toes and resulting in a triple-colour change starting with pallor and followed by cyanosis and erythema. Attacks are typically triggered by cold or emotional stress. The diagnosis of RP can be made on the basis of the patient’s clinical symptoms. Primary RP occurs without underlying disease and is considered a benign condition. A normal erythrocyte sedimentation rate, negative testing for antinuclear antibodies, normal nailfold capillaries and the absence of structural micro- or macrovascular damage and other diseases lead to the diagnosis of primary RP. Digital photoplethysmography and pulse contour analysis can be used as an additional tool to exclude structural macro- or microvascular disease. In contrast, secondary RP is associated with other diseases, mainly connective tissue diseases such as systemic sclerosis. If there is a suspicion of secondary RP, a thorough laboratory and vascular assessment is required to make the diagnosis of underlying disease. Acrocyanosis and erythromelalgia are additional functional vascular disorders that can be easily distinguished when patients are carefully assessed for their history and clinical symptoms.

[Intra-alveolar hemorrhage: rare presentation of fat pulmonary embolism].

PubMed

Ketata, W; Msaad, S; Bahloul, N; Marouen, F; Ayoub, A

2010-11-01

Fat embolism syndrome is a severe complication of long bone fractures, corresponding to the obstruction of small vessels by microdroplets of fat, originating from medulla ossium. Pulmonary involvement, present in 90% cases, makes the severity of the disease. We report the case of a 22-year-old man who presented, two days after industrial accident causing an opened tibial fracture, acute dyspnea with hemoptysis. Angio-CT-scan didn't show any proximal vascular obstruction, but parenchymal sections showed diffuse, bilateral and multifocal hyperdensities predominating at the periphery. Broncho-alveolar lavage brought a hemorrhagic liquid, with a high macrophage content and lipid inclusions in macrophages. Exams for the etiologic diagnosis of intra-alveolar hemorrhage were negative: renal function, 24-hour proteinuria, antinuclear antibodies, antineutrophil cytoplasmic antibodies. The diagnosis of intra-alveolar hemorrhage secondary to fat embolism was established. The outcome was spontaneously favorable. The occurrence of intra-alveolar hemorrhage in the course fat embolism is rarely reported. Its pathogenic mechanisms are not understood. It is mandatory to eliminate the other causes of alveolar hemorrhage before holding the diagnosis of fat embolism. Treatment is only symptomatic, based on respiratory reanimation. Copyright © 2010 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Drug-induced hepatitis superimposed on the presence of anti-SLA antibody: a case report

PubMed Central

Etxagibel, Aitziber; Julià, M Rosa; Brotons, Alvaro; Company, M Margarita; Dolz, Carlos

2008-01-01

Introduction Autoimmune hepatitis is a necroinflammatory disorder of unknown etiology characterized by the presence of circulating antibodies, hypergammaglobulinemia, and response to immunosuppression. It has the histological features of chronic hepatitis. The onset is usually insidious, but in some patients the presentation may be acute and occasionally severe. Certain drugs can induce chronic hepatitis mimicking autoimmune hepatitis. Different autoantibodies have been associated with this process but they are not detectable after drug withdrawal and clinical resolution. Case presentation We describe a case of drug-induced acute hepatitis associated with antinuclear, antisoluble liver-pancreas and anti-smooth muscle autoantibodies in a 66-year-old woman. Abnormal clinical and biochemical parameters resolved after drug withdrawal, but six months later anti-soluble liver-pancreas antibodies remained positive and liver biopsy showed chronic hepatitis and septal fibrosis. Furthermore, our patient has a HLA genotype associated with autoimmune hepatitis. Conclusion Patient follow-up will disclose whether our patient suffers from an autoimmune disease and if the presence of anti-soluble liver antigens could precede the development of an autoimmune hepatitis, as the presence of antimitochondrial antibodies can precede primary biliary cirrhosis. PMID:18226219

Defective B cell tolerance in adenosine deaminase deficiency is corrected by gene therapy

PubMed Central

Sauer, Aisha V.; Morbach, Henner; Brigida, Immacolata; Ng, Yen-Shing; Aiuti, Alessandro; Meffre, Eric

2012-01-01

Adenosine deaminase (ADA) gene defects are among the most common causes of SCID. Restoration of purine metabolism and immune functions can be achieved by enzyme replacement therapy, or more effectively by bone marrow transplant or HSC gene therapy (HSC-GT). However, autoimmune complications and autoantibody production, including anti-nuclear antibodies (ANAs), frequently occur in ADA-SCID patients after treatment. To assess whether ADA deficiency affects the establishment of B cell tolerance, we tested the reactivity of recombinant antibodies isolated from single B cells of ADA-SCID patients before and after HSC-GT. We found that before HSC-GT, new emigrant/transitional and mature naive B cells from ADA-SCID patients contained more autoreactive and ANA-expressing clones, indicative of defective central and peripheral B cell tolerance checkpoints. We further observed impaired B cell receptor (BCR) and TLR functions in B cells after ADA inhibition, which may underlie the defects in B cell tolerance. Strikingly, after HSC-GT, ADA-SCID patients displayed quasi-normal early B cell tolerance checkpoints, as evidenced by restored removal of developing autoreactive and ANA-expressing B cells. Hence, ADA plays an essential role in controlling autoreactive B cell counterselection by regulating BCR and TLR functions. PMID:22622038

Bruises on the ears and body.

PubMed

Sarmiento, Diana M; Northrup, Thomas F; Wah, Yu

2017-09-01

Over the course of a month, this 34-year-old woman had sought care at our facility--and another--on 3 separate occasions for painful bruises (visits #1 and #3) and deep vein thrombosis (visit #2). The bruises first appeared acutely on her arms, prompting her first visit to our ED and leading to a hospital stay. Several weeks later, the patient developed new bruise-like lesions on her earlobes, face, trunk, and lower extremities. In between these 2 visits, the patient was seen in another ED (and admitted) for right upper extremity DVT and was started on enoxaparin, followed by warfarin. The patient had no history of trauma, but did have a 7-year history of cocaine abuse. The initial bruises appeared one week after using cocaine from a different dealer. On her most recent visit, her vitals and physical examination were unremarkable, apart from the skin findings. Her complete blood count, complete metabolic panel, and urinalysis were unremarkable. On her previous admissions, the patient's urine drug test had been positive for cocaine. She'd also tested positive for cytoplasmic antineutrophil cytoplasmic antibodies, antinuclear antibodies, anti-double stranded DNA, and anticardiolipin IgM. WHAT IS YOUR DIAGNOSIS? HOW WOULD YOU TREAT THIS PATIENT?

[Coexistence of sarcoidosis and primary Sjögren syndrome: a clinical analysis and literature review].

PubMed

Song, X Y; Huang, H; Liu, Y Z; Zhao, Y Y; Li, S; Xu, Z J

2017-05-01

Four patients with coexistence of sarcoidosis and primary Sjögren syndrome (pSS) were retrospectively analyzed.All patients were female, who were referred to our department mainly because of respiratory symptoms.Positive antinuclear antibody(ANA) was detected in 2 patients and anti-Sjögrens syndrome A (SSA) antibody positive in 1 patient.All patients presented specific histologic patterns of both sarcoidosis and pSS.Publications related to coexistence of these two diseases were reviewed.Forty-one patients were finally included in the analysis, among whom 37 confirmed patients were from literature search.There were 37 women and 4 men.The main clinical features presentation were xerophthalmia in 40, xerostomia in 38, hilaradenopathies in 28, interstitial lung disease in 15, respiratory symptoms in 13.The main immunologic data were positive ANA in 23, SSA antibody in 19, anti-Sjögrens syndrome B antibody in 10 and rheumatoid factor in 12.All patients presented specific histologic patterns of both diseases.Patients with both sarcoidosis and pSS of ten represent multisystemic involvement and positive immunologic parameters, as well as the dual expression of specific histologic characteristics.

Susceptibility based upon Chemical Interaction with Disease ...

EPA Pesticide Factsheets

One of the challenges facing toxicology and risk assessment is that numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest is the potential for chemicals to interact with background aging and disease processes, an interaction that may yield cumulative damage, altered chemical potency, and increased disease incidence. This review outlines the interactions possible between chemicals and background disease and identifies the type of information needed to evaluate such interactions. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which allows the identification of vulnerable individuals based upon the level of risk biomarker. The impact of toxic chemicals on this biomarker can then be used to predict how the chemical modifies disease risk as long as related mechanistic and toxicological data are consistent with toxicant effect on the disease process. Several case studies are briefly presented which describe the toxic chemical, the clinical biomarker and the impacted disease including: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration rate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; trichloroethylene/increased anti-nuclear antibody/autoimmunity; dioxin/increased CYP1A1/hypertension. These case studies point o

Verrucous form of chilblain lupus erythematosus.

PubMed

Pock, L; Petrovská, P; Becvár, R; Mandys, V; Hercogová, J

2001-09-01

A 45-year-old woman had symmetrical livid plaques with yellowish hyperkeratoses for 5 years, which progressed on to the fingers and toes and on the soles of the feet. Two years later creamy, whitish areas and maceration appeared on the buccal mucosa and the lips. A skin biopsy revealed massive collagen hyaline degeneration in the perivascular area, hyperkeratosis and hypergranulosis, small lymphocyte infiltrates with several melanophages and extravasates of erythrocytes in the upper corium in perivascular areas and hydropic degeneration of basal keratinocytes. The findings using direct immunofluorescence were compatible with lupus erythematosus (LE). Laboratory investigation showed a slight leucopenia and thrombopenia, a slightly elevated erythrocyte sedimentation rate, hypocomplementaemia C3 and C4, a high titre of rheumatoid factor and antinuclear antibodies positivity of extractable nuclear antigen. The results reflected probably the development of a systemic form of the disease. The patient was successfully managed by methylprednisolone and hydroxychloroquine. After 1 year of therapy, a new skin biopsy revealed a substantial reduction of hyperkeratosis and hyaline degeneration of collagen tissue in the perivascular areas. The combination of the extensive hyperkeratosis and hyalinization thus seems to be features of the long-lasting, untreated lesions in chilblain LE.

Anti-DNA antibodies--quintessential biomarkers of SLE.

PubMed

Pisetsky, David S

2016-02-01

Antibodies that recognize and bind to DNA (anti-DNA antibodies) are serological hallmarks of systemic lupus erythematosus (SLE) and key markers for diagnosis and disease activity. In addition to common use in the clinic, anti-DNA antibody testing now also determines eligibility for clinical trials, raising important questions about the nature of the antibody-antigen interaction. At present, no 'gold standard' for serological assessment exists, and anti-DNA antibody binding can be measured with a variety of assay formats, which differ in the nature of the DNA substrates and in the conditions for binding and detection of antibodies. A mechanism called monogamous bivalency--in which high avidity results from simultaneous interaction of IgG Fab sites with a single polynucleotide chain--determines anti-DNA antibody binding; this mechanism might affect antibody detection in different assay formats. Although anti-DNA antibodies can promote pathogenesis by depositing in the kidney or driving cytokine production, they are not all alike, pathologically, and anti-DNA antibody expression does not necessarily correlate with active disease. Levels of anti-DNA antibodies in patients with SLE can vary over time, distinguishing anti-DNA antibodies from other pathogenic antinuclear antibodies. Elucidation of the binding specificities and the pathogenic roles of anti-DNA antibodies in SLE should enable improvements in the design of informative assays for both clinical and research purposes.

Primary Sjögren's syndrome with diffuse cystic lung changes developed systemic lupus erythematosus: a case report and literature review.

PubMed

Liu, Xiao; Li, Hao; Yin, Yunhong; Ma, Dedong; Qu, Yiqing

2017-05-23

Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease that can occur as a unique existence (primary Sjögren's syndrome) or merge with other systemic diseases like systemic lupus erythematosus (SLE), rheumatoid arthritis or systemic sclerosis (secondary Sjögren's syndrome). Data on the two diseases occurrence order are inadequate. Primary Sjögren's syndrome (pSS) may relatively uncommonly lead to diffuse cystic lung changes. We represent a female who was diagnosed pSS with diffuse cystic lung alterations developed SLE two years later. SS was diagnosed on account of the existence of dryness of eye and mouth, Schirmer's test, biopsy of the minor salivary glands of her lip, positive anti-SSA and anti-SSB antibody in the serum. Chest computed tomography image showed bilateral diffuse cystic changes with a wide variation in cyst size and distribution. SLE was finally diagnosed based on bilateral lower limb skin rash, gonarthritis and omarthritis, low level of complement, antinuclear antibody 1:640 and positive antibodies to double-stranded DNA. Improvement was achieved with therapy of corticosteroids, hydroxychloroquine and antibiotics. This report provides us clinical, diagnosis and treatment perception of SS-onset SLE as patient presenting diffuse cystic lung changes.

Non-organ-specific autoantibodies in chronic hepatitis C patients: association with histological activity and fibrosis.

PubMed

Chrétien, P; Chousterman, M; Abd Alsamad, I; Ozenne, V; Rosa, I; Barrault, C; Lons, T; Hagège, H

2009-01-01

Non-organ-specific autoantibodies (NOSAs) are frequently found in the sera of patients with Hepatitis C Virus (HCV) infection. However, no conclusive answers have been produced concerning the clinical relevance of these antibodies. To determine whether a relationship might exist between the presence of NOSA and the severity of liver disease in chronic hepatitis C. 186 treatment-naïve chronic hepatitis C patients were studied consecutively for autoantibodies. Liver biopsies were analyzed according to the Metavir score. NOSAs were present in 75 patients (40%). Anti-nuclear antibodies were found in 32% of patients (speckled pattern), anti-smooth muscle in 15% without F-actin specificity, anti-mitochondria in 0.5%, and anti-LKM1 in 0.5%, respectively. No liver-cytosol1 or soluble liver antigen antibodies were detected. There was a highly significant correlation between the positivity of NOSA and the degree of inflammation and hepatocellular injury (p = 0.001) and also with the degree of fibrosis (p < 0.0001). The presence of NOSA was associated with higher aspartate aminotransferase, gamma-glutamyl-transpeptidase, gamma-globulin and immunoglobulin G levels. By contrast, no differences were observed regarding age, gender, route of infection, duration of disease, HCV genotypes or viral load. NOSAs were associated with the most severe forms of chronic HCV infections.

Autoantibodies and their antigens in autoimmune hepatitis.

PubMed

Bogdanos, Dimitrios P; Mieli-Vergani, Giorgina; Vergani, Diego

2009-08-01

Autoantibody detection assists in the diagnosis and allows differentiation of autoimmune hepatitis (AIH) type 1 (AIH-1), characterized by antinuclear antibody (ANA) and/or smooth muscle antibody (SMA), and type 2 (AIH-2), distinguished by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) and/or antibodies to liver cytosol type 1 (anti-LC1). Detection of atypical perinuclear antineutrophil cytoplasmic antibodies (pANCA) and anti-soluble liver antigen (SLA) antibodies can act as an additional pointer toward the diagnosis of AIH, particularly in the absence of the conventional autoantibodies. Routine autoantibody testing by indirect immunofluorescence has been recently complemented by molecular assays based on purified or recombinant antigens. Although the AIH-1-specific ANA and SMA targets need better definition, those of anti-LKM1 and anti-LC1 in AIH-2 have been clearly identified; the fine specificity of antibody reactivity and its clinical relevance to disease pathogenesis are the focus of ongoing investigation. This article critically discusses the current knowledge of the diagnostic and clinical significance of AIH-related autoantibody reactivities, focusing on key issues that the physician needs to be aware of to be able to request the appropriate testing and to interpret correctly the laboratory results within the clinical context of the patient. Copyright Thieme Medical Publishers.

Erythrocyte sedimentation rate as baseline predictor for the development of uveitis in children with juvenile idiopathic arthritis.

PubMed

Haasnoot, Arenda J W; van Tent-Hoeve, Maretta; Wulffraat, Nico M; Schalij-Delfos, Nicoline E; Los, Leonoor I; Armbrust, Wineke; Zuithoff, Nicolaas P A; de Boer, Joke H

2015-02-01

To analyze inflammatory parameters as possible predictors for the development of uveitis in juvenile idiopathic arthritis (JIA) patients. Further, to analyze the predictive value of demographic and clinical factors at the onset of arthritis. Retrospective cohort study. In 358 children with oligoarthritis and rheumatoid factor-negative polyarthritis, erythrocyte sedimentation rate (ESR), C-reactive protein, leukocyte count, presence of antinuclear antibodies (ANA), presence of human leukocyte antigen (HLA-)B27, age of onset of JIA, and sex were analyzed for their predictive value for the onset of uveitis. One hundred forty-seven patients (41%) were diagnosed with chronic anterior uveitis. Young age of onset, presence of ANA, and elevated ESR appeared to be predictive factors according to univariate analyses (P = .029, P = .007, and P = 5E(-4), respectively). According to multivariate analysis, young age of onset and elevated ESR appeared to be predictive after adjusting for the other relevant factors (P = .004 and P = .001, respectively). A prediction model was developed. Elevated ESR appears to be a predictor for the occurrence of uveitis in patients with JIA. Since ESR is already routinely tested in patients with recently diagnosed arthritis, its use as a biomarker can easily be implemented in daily practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Increased Susceptibility to Chemical Toxicity with Pre-existing ...

EPA Pesticide Factsheets

Numerous host and environmental factors may modulate vulnerability and risk. An area of increasing interest to risk assessors is the potential for chemicals to interact with pre-existing diseases and aging that may yield cumulative damage, altered chemical response, and increased disease susceptibility. We evaluated the relationships between chemicals and pre-existing disease and identify the type of information needed to evaluate the relationships of interest. Key among these is the existence of a clinically relevant and easy to measure biomarker of disease risk which is also modulated by a particular chemical of interest. This biomarker may be a physiological, biochemical, or genetic indicator that corresponds to a phase of the disease process and may be an indicator of where an individual is on the continuum of disease or health status. The relationship between chemical exposure and a biomarker may then be used to predict how preexisting conditions may modify health risks of chemical exposures. Several case studies are explored to describe the toxic chemical, the clinical biomarker, the impacted disease and the evidence that the chemical enhances disease risk: fine particulate matter/decreased heart rate variability/increased cardiopulmonary events; cadmium/decreased glomerular filtration ate/increased chronic kidney disease; methyl mercury/decreased paraoxonase-1/increased cardiovascular risk; Trichloroethylene/increased anti-nuclear antibody/autoimmunit

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): An Uncommon Manifestation of Systemic Lupus Erythematosus (SLE).

PubMed

Abraham, Hrudya; Kuzhively, Jose; Rizvi, Syed W

2017-09-12

BACKGROUND Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon manifestation of systemic lupus erythematosus (SLE). We report a case of SLE presenting as CIDP and discuss the diagnosis, management, and prognosis of CIDP. CASE REPORT A 40-year-old woman with a past medical history of SLE treated with hydroxychloroquine presented with bilateral, progressive, ascending, sensory and motor neuropathy. Physical examination showed weakness and reduced temperature of all extremities, reduced pinprick and vibration sense of the distal extremities, loss of reflexes, and walking with a wide-based unsteady gait. Laboratory investigations showed positive antinuclear antibodies (ANA), anti-(smooth muscle (SM) antibody, anti-RNP antibody, anti-SSA antibody, anti-ds-DNA antibody, and an erythrocyte sedimentation rate (ESR) of 75 mm/hr, low C4, leukopenia, and anemia. Electromyography (EMG) confirmed the diagnosis of CIDP. The patient's neuropathy and muscle weakness improved on treatment with intravenous immunoglobulin (IVIG) and high-dose steroids. CONCLUSIONS The early clinical diagnosis of CIDP, supported by serological autoantibody profiles associated with SLE, can predict a good response to steroids. Most patients with CIDP are treated successfully with steroids if the diagnosis is made early. IVIG, plasmapheresis, or immunosuppressive therapy should be considered if there is no response to steroids.

Pesticides, chemical and industrial exposures in relation to systemic lupus erythematosus

PubMed Central

Parks, Christine G.; De Roos, Anneclaire J.

2013-01-01

Growing evidence suggests exposure to chemicals and industrial pollutants may increase risk of SLE. Here we review research on SLE associations with occupational and industrial exposures, primarily drawing on studies in human populations and summarizing epidemiologic research published in the past decade. The association of occupational silica exposure with SLE is well established, but key questions remain, including the required dose and susceptibility factors, and SLE risk due to other silicate exposures. Research on SLE and other exposures is less well developed, though several potential associations merit further consideration due to the consistency of preliminary human findings, experimental animal research, and biologic plausibility. These include pesticides and solvents, for which experimental findings also support investigation of specific agents, including organochlorines and trichloroethylene. Experimental findings and biologic plausibility suggest research on SLE and occupational exposure to hydrocarbons (i.e., mineral oils) is warranted, especially given the widespread exposures in the population. Experimental and limited human findings support further investigation of SLE related to mercury exposure, especially in dental occupations. Research on environmental risk factors in risk-enriched cohorts (family based) is recommended, as is further investigation of exposures in relation to intermediate markers of effect (e.g., antinuclear antibodies), clinical features (e.g., nephritis) and outcomes. PMID:24763537

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase in nuclei and rimmed vacuoles of muscle fibers in DMRV (distal myopathy with rimmed vacuoles).

PubMed

Ishihara, Shoichiro; Tomimitsu, Hiroyuki; Fujigasaki, Hiroto; Saito, Fumiaki; Mizusawa, Hidehiro

2008-03-01

UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) is a key molecule in the pathogenesis of distal myopathy with rimmed vacuoles (DMRV) and hereditary inclusion body myopathy (HIBM) and almost all such patients have some mutations in GNE. However, subcellular localization of GNE and the mechanism of muscular damage have not been clarified. A rabbit polyclonal antibody for GNE was prepared. Immunohistochemistry was performed using anti-GNE and anti-nuclear protein antibodies. Western blotting with subcellular fractionated proteins was performed to determine subcellular localization of GNE. The sizes of myonuclei were quantified in muscle biopsies from patients with DMRV and amyotrophic lateral sclerosis (ALS). In DMRV muscles, immunohistochemistry identified GNE in sarcoplasm and specifically in myonuclei and rimmed vacuoles (RV). Nuclear proteins were also found in RVs. Immunohistochemistry showed colocalization of GNE and emerin in C2C12 cells. Western blotting revealed the presence of GNE in nuclear fractions of human embryonic kidney (HEK) 293T cells. The mean size of myonuclei of DMRV was significantly larger than that of ALS. GNE is present in myonuclei near nuclear membrane. Our results suggest that myonuclei are involved in RV formation in DMRV, and that mutant GNE in myonuclei seems to play some role in this process.

γδ T cells affect IL-4 production and B-cell tolerance

PubMed Central

Huang, Yafei; Heiser, Ryan A.; Detanico, Thiago O.; Getahun, Andrew; Kirchenbaum, Greg A.; Casper, Tamara L.; Aydintug, M. Kemal; Carding, Simon R.; Ikuta, Koichi; Huang, Hua; Cambier, John C.; Wysocki, Lawrence J.; O’Brien, Rebecca L.; Born, Willi K.

2015-01-01

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4–producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4–regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4–inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance. PMID:25535377

γδ T cells affect IL-4 production and B-cell tolerance.

PubMed

Huang, Yafei; Heiser, Ryan A; Detanico, Thiago O; Getahun, Andrew; Kirchenbaum, Greg A; Casper, Tamara L; Aydintug, M Kemal; Carding, Simon R; Ikuta, Koichi; Huang, Hua; Cambier, John C; Wysocki, Lawrence J; O'Brien, Rebecca L; Born, Willi K

2015-01-06

γδ T cells can influence specific antibody responses. Here, we report that mice deficient in individual γδ T-cell subsets have altered levels of serum antibodies, including all major subclasses, sometimes regardless of the presence of αβ T cells. One strain with a partial γδ deficiency that increases IgE antibodies also displayed increases in IL-4-producing T cells (both residual γδ T cells and αβ T cells) and in systemic IL-4 levels. Its B cells expressed IL-4-regulated inhibitory receptors (CD5, CD22, and CD32) at diminished levels, whereas IL-4-inducible IL-4 receptor α and MHCII were increased. They also showed signs of activation and spontaneously formed germinal centers. These mice displayed IgE-dependent features found in hyper-IgE syndrome and developed antichromatin, antinuclear, and anticytoplasmic autoantibodies. In contrast, mice deficient in all γδ T cells had nearly unchanged Ig levels and did not develop autoantibodies. Removing IL-4 abrogated the increases in IgE, antichromatin antibodies, and autoantibodies in the partially γδ-deficient mice. Our data suggest that γδ T cells, controlled by their own cross-talk, affect IL-4 production, B-cell activation, and B-cell tolerance.

Anti-brain autoantibodies in the serum of schizophrenic patients: a case-control study.

PubMed

Margari, Francesco; Petruzzelli, Maria Giuseppina; Mianulli, Rossana; Toto, Maddalena; Pastore, Adriana; Bizzaro, Nicola; Tampoia, Marilina

2013-12-30

Schizophrenia is considered a neurodevelopmental disorder with a multifactorial pathogenesis where autoimmune factors may play a significant role. The aim of this study was to verify the presence of anti-brain autoantibodies in the serum of schizophrenic patients compared to healthy controls. Autoantibodies against brain were detected by the immunofluorescence method, utilizing sections of rat hippocampus and hypothalamus and of monkey cerebellum. Three different fluorescence patterns were observed, staining the nucleus-cytoplasm of neurons, the neuroendothelial of blood vessel and the neurofilaments. Search for other organ-specific and non organ-specific autoantibodies was performed in all sera by indirect immunofluorescence method, enzyme linked immunosorbent assay and chemiluminescence immunoassay. Results showed a significant association between schizophrenia and anti-brain autoantibodies against the neuroendothelium of blood vessel in hypothalamus, hippocampus and cerebellum; a significant nuclear and cytoplasmic staining of neurons was assessed only for the hippocampus. No other significant association was found, except between schizophrenia and anti-nuclear autoantibodies on HEp-2 cells. In conclusion, these results support the hypothesis of a significant association between schizophrenia and circulating anti-brain autoantibodies, suggesting a diffuse reactivity against the neuroendothelium of blood vessel and highlighting a nuclear and cytoplasmic staining of the neurons of hippocampus. © 2013 Published by Elsevier Ireland Ltd.

Current trends of reproductive immunology practices in in vitro fertilization (IVF) - a first world survey using IVF-Worldwide.com.

PubMed

Kwak-Kim, Joanne; Han, Ae Ra; Gilman-Sachs, Alice; Fishel, Simon; Leong, Milton; Shoham, Zeev

2013-01-01

Reproductive immunology has evolved from basic research studies to clinical applications. In this study, we aim to investigate the actual application of reproductive immunology concepts and findings in clinical reproductive medicine such as recurrent pregnancy losses (RPL), repeated implantation failures (RIF), and failed in vitro fertilization (IVF) cycles. A web-based survey was performed on IVF-Worldwide.com. Collected data were analyzed by the computerized software. A significant proportion of physicians recommend thrombophilia workups (86%), parental genetic study (79%), and immunologic evaluations (69%) to IVF candidates who have a history of RPL or chemical pregnancy losses. IVF physicians consider an immunologic workup when patients have two (30%) or three (21%) failed IVF cycles. Assays for anticardiolipin antibody, lupus anticoagulant, thyroid peroxidase antibody, and antinuclear antibody are the four most commonly ordered immunologic tests for RPL (88, 84, 50, 47% each) and RIF (68, 63, 38, 38% each). Cellular immune evaluations, such as NK assay, human leukocyte antigen study, Th1/Th2 study or immunophenotype assay, are less commonly ordered. Reproductive immunology principles have been applied to the clinical management of RPL, RIF, and failed IVF cycles, and a significant proportion of IVF physicians acknowledge the importance of immunologic alterations with reproductive outcomes. © 2012 John Wiley & Sons A/S.

Inhibition of adenovirus DNA synthesis in vitro by sera from patients with systemic lupus erythematosus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horwitz, M.S.; Friefeld, B.R.; Keiser, H.D.

1982-12-01

Sera containing antinuclear antibodies from patients with systemic lupus erythematosus (SLE) and related disorders were tested for their effect on the synthesis of adenovirus (Ad) DNA in an in vitro replication system. After being heated at 60/sup 0/C for 1 h, some sera from patients with SLE inhibited Ad DNA synthesis by 60 to 100%. Antibodies to double-stranded DNA were present in 15 of the 16 inhibitory sera, and inhibitory activity copurified with anti-double-stranded DNA in the immunoglobulin G fraction. These SLE sera did not inhibit the DNA polymerases ..cap alpha.., BETA, ..gamma.. and had no antibody to the 72,000-daltonmore » DNA-binding protein necessary for Ad DNA synthesis. The presence of antibodies to single-stranded DNA and a variety of saline-extractable antigens (Sm, Ha, nRNP, and rRNP) did not correlate with SLE serum inhibitory activity. Methods previously developed for studying the individual steps in Ad DNA replication were used to determine the site of inhibition by the SLE sera that contained antibody to double-stranded DNA. Concentrations of the SLE inhibitor that decreased the elongation of Ad DNA by greater than 85% had no effect on either the initiation of Ad DNA synthesis or the polymerization of the first 26 deoxyribonucleotides.« less

Systems biology of lupus: mapping the impact of genomic and environmental factors on gene expression signatures, cellular signaling, metabolic pathways, hormonal and cytokine imbalance, and selecting targets for treatment.

PubMed

Perl, Andras

2010-02-01

Systemic lupus erythematosus (SLE) is characterized by the dysfunction of T cells, B cells, and dendritic cells, the release of pro-inflammatory nuclear materials from necrotic cells, and the formation of antinuclear antibodies (ANA) and immune complexes of ANA with DNA, RNA, and nuclear proteins. Activation of the mammalian target of rapamycin (mTOR) has recently emerged as a key factor in abnormal activation of T and B cells in SLE. In T cells, increased production of nitric oxide and mitochondrial hyperpolarization (MHP) were identified as metabolic checkpoints upstream of mTOR activation. mTOR controls the expression T-cell receptor-associated signaling proteins CD4 and CD3zeta through increased expression of the endosome recycling regulator Rab5 and HRES-1/Rab4 genes, enhances Ca2+ fluxing and skews the expression of tyrosine kinases both in T and B cells, and blocks the expression of Foxp3 and the generation of regulatory T cells. MHP, increased activity of mTOR, Rab GTPases, and Syk kinases, and enhanced Ca2+ flux have emerged as common T and B cell biomarkers and targets for treatment in SLE.

Culture and the environment in France

NASA Astrophysics Data System (ADS)

Duclos, Denis H.; Smadja, Jocelyne J.

1985-03-01

Although the French concern for environmental protection dates back several centuries, a committed movement toward environmental protection did not begin until the second half of the 19th century. The Romantic influence of Rousseau and others led to the formation of various societies aimed at protecting the French landscape. Until the most recent environmental crusades of the 1960s and 1970s, the cause of protecting the natural environment seemed to fall largely on the shoulders of scientists and anglers, who voiced their concern over increasing environmental degradation in pamphlets and recreational journals. Their pressure aided in the passage of legislation on water quality. During the 1960s, environmental organizations proliferated and, in league with student activists, played an important role in raising the environmental consciousness of the French. During the 1970s, these activists began to turn to traditional political mobilization as a way of drawing attention to their platform. Environmental activism reached its peak with the antinuclear rallies of the late 1970s. By the end of the 1970s, many environmental associations had grown up in the French culture, but the future of environmentalism remains questionable owing to a number of economic realities, including the oil crisis, which made nuclear power much more acceptable to the public.

Livedoid vasculopathy in a patient with factor V mutation (Leiden).

PubMed

Biedermann, T; Flaig, M J; Sander, C A

2000-09-01

Frequently, no underlying disease can be detected in patients with livedoid vasculopathy. For these forms, an unknown vaso-occlusive or thrombogenic process has been accused to play a role. Thus, a patient with livedoid vasculopathy was examined for different parameters which can be involved in coagulopathies. Laboratory studies for different autoantigen reactive immunoglobulins, cryoglobulins, and circulating immune complexes were carried out. Besides dermatopathologic examination, a biopsy specimen was analyzed by direct immunofluorescence for immunoglobulin (Ig) and complement deposits. Furthermore, hemostaseological function tests including activated protein C (APC) resistance were undertaken. Positive only at very low titres were antinuclear antibodies and c-ANCA, all other parameters were within normal ranges or negative. Direct immunofluorescence revealed IgM, C3 and fibrogen deposits. Hemostaseological function tests demonstrated a pathologic activated protein c resistance and PCR analysis a heterozygous defect of the factor V (Leiden). The diagnosis of livedoid vasculopathy associated with factor V mutation (Leiden) was made. Since the underlying cause for livedoid vasculopathy often remains unknown, we suggest that hemostaseological function tests including APC resistance and factor V gene mutation analysis should be carried out. Further studies have to follow in order to elucidate the role of mutant factor V in livedoid vasculopathy and in cutaneous ulcerations.

Systemic sclerosis in Argentina: evaluation of a large cohort from a single centre and comparison with other international series.

PubMed

Scolnik, M; Lancioni, E; Saucedo, C; Marin, J; Sabelli, M; Bedran, Z; Soriano, E R; Catoggio, L J

2014-01-01

Prevalence of systemic sclerosis (SSc) and different clinical subsets varies across the world. Few data have been published on SSc patients in Latin America. Our objective was to describe a SSc cohort in Argentina and to compare clinical findings, disease subsets and antibodies with other international SSc populations. Patients with SSc (n=234) seen at the Rheumatology section of the Hospital Italiano de Buenos Aires between 2000-2011 were retrospectively analysed. Data on clinical manifestations, disease subsets and antibodies were obtained. Patients were classified into diffuse cutaneous (dc) and limited cutaneous (lc) subsets. Comparison with other cohorts (France, United States, Germany, Italy, Mexico, EUSTAR and Brazil) was made based on published information. A higher female:male ratio (12:1) and a higher limited subset prevalence (76.1%) was found in this Argentine cohort comparing with others. We also found a lower prevalence of diffuse disease, anti Scl-70 (antitopoisomerase) and nucleolar pattern antinuclear antibodies. Within each subset, clinical findings were similar with other SSc populations except for a very low prevalence in renal crisis (0.02% of dc SS). With slight variations perhaps due to genetic, environmental or referral factors, SSc in this cohort appears to be similar to that described in other parts of the world.

A Case of Paraneoplastic Remitting Seronegative Symmetrical Synovitis with Pitting Edema Syndrome Improved by Chemotherapy

PubMed Central

Sakamoto, Takahiko; Ota, Shuji; Haruyama, Terunobu; Ishihara, Masashi; Natsume, Maika; Fukasawa, Yoko; Tanzawa, Shigeru; Usui, Ryo; Honda, Takeshi; Ichikawa, Yasuko; Watanabe, Kiyotaka; Seki, Nobuhiko

2017-01-01

The patient was a 69-year-old male who had started experiencing acute-onset pain in both shoulder joints and edema of both hands and feet. His symptoms progressively worsened within 1 month. Laboratory data indicated elevated CRP and erythrocyte sedimentation rate despite the normal range of antinuclear antibodies and rheumatoid factor and normal organ function. Furthermore, imaging data of the hand indicated synovitis without bone erosions. Meanwhile, chest CT revealed a lung tumor, leading to a diagnosis of primary lung adenocarcinoma with EGFR mutation (cT2aN3M0, stage IIIB). Based on these findings, he was diagnosed as suffering from paraneoplastic remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. Thereafter, his symptoms disappeared as the tumor size was rapidly decreased by gefitinib therapy for lung adenocarcinoma. Currently, RS3PE syndrome can be classified as a vascular endothelial growth factor (VEGF)-associated disorder. Given that his symptoms improved by chemotherapy, the present case further supported the possible hypothesis that paraneoplastic RS3PE syndrome might be caused by tumor-induced VEGF. Therefore, the present case suggested that the symptoms of acute-onset joint pain accompanied by pitting edema in elderly patients should be considered suspicious for a malignant tumor, thereby warranting a detailed full-body examination. PMID:29430239

Case of remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome) showing dermatomyositis-like eruption.

PubMed

Takeda, Kiminobu; Fujita, Jun; Fujii, Toshiki; Tanabe, Hiroshi; Mochizuki, Takashi; Yanagihara, Makoto

2010-01-01

A 73-year-old woman developed linear erythema at the sites of scratching-induced scars on the bilateral thighs 2 weeks before the initial consultation. Subsequently, edematous erythema developed in the upper eyelids, dorsum of the nose and the face, and pitting edema in the dorsum of the bilateral hands and feet. The C-reactive protein (CRP) level was 8.2 mg/dL and erythrocyte sedimentation rate (ESR) 121 mm/h. The antinuclear antibody titer was 1:160, and rheumatoid factor (RF) and anti-Jo-1 antibody were negative. X-ray examination of the bilateral hands showed neither narrowing of the joint spaces nor bone erosion. Ga scintigraphy showed synovitis of the bilateral wrists. A diagnosis of remitting seronegative symmetrical synovitis with pitting edema syndrome (RS3PE) was made. The erythema disappeared after diclofenac sodium administration. However, because the joint swelling and pitting edema did not improve, p.o. administration of prednisolone (20 mg/day) was initiated. The CRP and ESR levels normalized 2 months after the initiation of administration, and pitting edema disappeared after 3 months. We report this case because linear erythema like that observed in dermatomyositis has not been described as eruptions associated with RS3PE.

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed Central

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-01-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually. PMID:12923344

Sjogren's syndrome presenting as remitting seronegative symmetric synovitis with pitting edema (RS3PE).

PubMed

Choi, Young Mi; Sheen, Dong Hyuk; Lee, Yun Jong; Lee, Eun Bong; Song, Yeong Wook

2003-08-01

Remitting seronegative symmetric synovitis with pitting edema (RS3PE) syndrome is characterized by symmetrical and acute synovitis, pitting edema, the absence of rheumatoid factor, increased acute phase reactants, lack of bony erosions on radiography, and benign and short clinical course. Half of all patients with Sjogren's syndrome experience arthritis during the disease course. We here describe the first case of Sjogren's syndrome presenting as RS3PE. She had swelling in knees, ankles, and wrists. After then the swelling spread to her lower legs, feet, face, and both hands. She was admitted to another hospital and was suspected of lupus or rheumatoid arthritis. Three months later, she had dry mouth and had lower lip biopsy. She was admitted to this hospital due to development of swelling in face and lower legs for 3 days. On physical examination, she had pitting edema in both hands and feet dorsum. Laboratory test showed elevated erythrocyte sedimentation rate, positivity of rheumatoid factor, anti-nuclear antibody, and anti-Ro antibody. There was no erosion in the hands radiography. Schirmer's test and lip biopsy was compatible with Sjogren's syndrome. She was diagnosed RS3PE and Sjogren's syndrome. She was begun with prednisolone and her symptoms improved gradually.

Computer-Assisted Classification Patterns in Autoimmune Diagnostics: The AIDA Project

PubMed Central

Benammar Elgaaied, Amel; Cascio, Donato; Bruno, Salvatore; Ciaccio, Maria Cristina; Cipolla, Marco; Fauci, Alessandro; Morgante, Rossella; Taormina, Vincenzo; Gorgi, Yousr; Marrakchi Triki, Raja; Ben Ahmed, Melika; Louzir, Hechmi; Yalaoui, Sadok; Imene, Sfar; Issaoui, Yassine; Abidi, Ahmed; Ammar, Myriam; Bedhiafi, Walid; Ben Fraj, Oussama; Bouhaha, Rym; Hamdi, Khouloud; Soumaya, Koudhi; Neili, Bilel; Asma, Gati; Lucchese, Mariano; Catanzaro, Maria; Barbara, Vincenza; Brusca, Ignazio; Fregapane, Maria; Amato, Gaetano; Friscia, Giuseppe; Neila, Trai; Turkia, Souayeh; Youssra, Haouami; Rekik, Raja; Bouokez, Hayet; Vasile Simone, Maria; Fauci, Francesco; Raso, Giuseppe

2016-01-01

Antinuclear antibodies (ANAs) are significant biomarkers in the diagnosis of autoimmune diseases in humans, done by mean of Indirect ImmunoFluorescence (IIF) method, and performed by analyzing patterns and fluorescence intensity. This paper introduces the AIDA Project (autoimmunity: diagnosis assisted by computer) developed in the framework of an Italy-Tunisia cross-border cooperation and its preliminary results. A database of interpreted IIF images is being collected through the exchange of images and double reporting and a Gold Standard database, containing around 1000 double reported images, has been settled. The Gold Standard database is used for optimization of a CAD (Computer Aided Detection) solution and for the assessment of its added value, in order to be applied along with an Immunologist as a second Reader in detection of autoantibodies. This CAD system is able to identify on IIF images the fluorescence intensity and the fluorescence pattern. Preliminary results show that CAD, used as second Reader, appeared to perform better than Junior Immunologists and hence may significantly improve their efficacy; compared with two Junior Immunologists, the CAD system showed higher Intensity Accuracy (85,5% versus 66,0% and 66,0%), higher Patterns Accuracy (79,3% versus 48,0% and 66,2%), and higher Mean Class Accuracy (79,4% versus 56,7% and 64.2%). PMID:27042658

A case of polyglandular autoimmune syndrome type III complicated with autoimmune hepatitis.

PubMed

Oki, Kenji; Yamane, Kiminori; Koide, Junko; Mandai, Koichi; Nakanishi, Shuhei; Fujikawa, Rumi; Kohno, Nobuoki

2006-10-01

A 58-year-old woman complaining of finger tremor was referred to our hospital. The diagnosis of Graves' disease was made based on increased free triiodothyronine (18.88 pg/ml) and free thyroxine (7.47 ng/dl), low TSH (<0.005 microIU/ml) and increased TSH receptor binding antibody activity (70.9%). Serum level of AST (62 U/l) and ALT (93 U/l) were increased and liver biopsy revealed linkage of adjacent portal areas by lymphoplasmacytic infiltrates and fibrosis with piecemeal necrosis. Although antinuclear antibody was negative, these findings indicated that she had autoimmune hepatitis (AIH) according to the criteria of the International Autoimmune Hepatitis Scoring System. Slowly progressive type 1 diabetes mellitus (DM) was confirmed by a diabetic response pattern due to 75 g-oral glucose tolerance test, and seropositivity towards anti-glutamic acid decarboxylase (725 U/ml) and islet cell (80 JDF Units) antibodies. This case exhibited an extremely rare combination of three different autoimmune diseases, including Graves' disease, slowly progressive type 1 DM and AIH, and had no known sensitive human leukocyte antigen (HLA) typing or haplotype for these disorders. Although it is common for patients with Graves' disease to exhibit abnormal liver function, it is important to make an accurate diagnosis of AIH because of this life-threatening disorder.

Antineutrophil cytoplasm antibody: positivity and clinical correlation.

PubMed

Martínez Téllez, Goitybell; Torres Rives, Bárbara; Rangel Velázquez, Suchiquil; Sánchez Rodríguez, Vicky; Ramos Ríos, María Antonia; Fuentes Smith, Lisset Evelyn

2015-01-01

To determine positivity and clinical correlation of anti-neutrophil cytoplasmic antibodies (ANCA), taking into account the interference of antinuclear antibodies (ANA). A prospective study was conducted in the Laboratory of Immunology of the National Cuban Center of Medical Genetic during one year. Two hounded sixty-seven patients with indication for ANCA determination were included. ANCA and ANA determinations with different cut off points and assays were determined by indirect immunofluorescense. Anti proteinase 3 and antimyeloperoxidase antibodies were determined by ELISA. Most positivity for ANCA was seen in patients with ANCA associated, primary small-vessel vasculitides, rheumatoid arthritis and systemic lupus erythematosus. Presence of ANCA without positivity for proteinase 3 and myeloperoxidase was higher in patients with ANA and little relation was observed between the perinuclear pattern confirmed in formalin and specificity by myeloperoxidase. Highest sensibility and specificity values for vasculitides diagnostic were achieved by ANCA determination using indirect immunofluorescense with a cut off 1/80 and confirming antigenic specificities with ELISA. ANCA can be present in a great number of chronic inflammatory or autoimmune disorders in the population studied. This determination using indirect immunofluorescence and following by ELISA had a great value for vasculitis diagnosis. Anti mieloperoxidasa assay has a higher utility than the formalin assay when ANA is present. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Differential Effect of Helicobacter pylori Eradication on Time-Trends in Brady/Hypokinesia and Rigidity in Idiopathic Parkinsonism

PubMed Central

Dobbs, Sylvia M; Dobbs, R John; Weller, Clive; Charlett, André; Bjarnason, Ingvar T; Lawson, Andrew J; Letley, Darren; Harbin, Lucy; Price, Ashley B; Ibrahim, Mohammad A A; Oxlade, Norman L; Bowthorpe, James; Leckstroem, Daniel; Smee, Cori; Plant, J Malcolm; Peterson, Dale W

2010-01-01

Background: We examine the effect of eradicating Helicobacter in idiopathic parkinsonism (IP). Marked deterioration, where eradication-therapy failed, prompted an interim report in the first 20 probands to reach de-blinding. The null-hypothesis, “eradication has no effect on principal outcome, mean stride length at free-walking speed,” was rejected. We report on study completion in all 30 who had commenced post-treatment assessments. Methods: This is a randomized, placebo-controlled, parallel-group efficacy study of eradicating biopsy-proven (culture and/or organism on histopathology) Helicobacter pylori infection on the time course of facets of IP, in probands taking no, or stable long-t½, anti-parkinsonian medication. Persistent infection at de-blinding (scheduled 1-year post-treatment) led to open active eradication-treatment. Results: Stride length improved (73 (95% CI 14–131) mm/year, p = .01) in favor of “successful” blinded active over placebo, irrespective of anti-parkinsonian medication, and despite worsening upper limb flexor rigidity (237 (57–416) Nm × 10−3/year, p = .01). This differential effect was echoed following open active, post-placebo. Gait did not deteriorate in year 2 and 3 post-eradication. Anti-nuclear antibody was present in all four proven (two by molecular microbiology only) eradication failures. In the remainder, it marked poorer response during the year after eradication therapy, possibly indicating residual “low-density” infection. We illustrate the importance of eradicating low-density infection, detected only by molecular microbiology, in a proband not receiving anti-parkinsonian medication. Stride length improved (424 (379–468) mm for 15 months post-eradication, p = .001), correction of deficit continuing to 3.4 years. Flexor rigidity increased before hydrogen-breath-test positivity for small intestinal bacterial overgrowth (208 (28–388) Nm × 10−3, p = .02), increased further during (171 (67–274), p = .001) (15–31 months), and decreased (136 (6–267), p = .04) after restoration of negativity (32–41 months). Conclusion: Helicobacter is an arbiter of progression, independent of infection-load. PMID:20633189

Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome: A cross-sectional analysis.

PubMed

Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

2016-07-01

There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients.We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ test or the Mann-Whitney U test for normally distributed or skewed data, respectively.The anti-dsDNA showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.042) but not TBUT. The C3 showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.014) but not TBUT. No correlations of dry eye parameters were observed between C4, ESR, and ANA.The major finding of this study was that the severity of dry eye syndrome in SLE patients without sSS was strongly correlated with anti-dsDNA and C3 but not with C4, ESR, and ANA.

Severity of dry eye syndrome is related to anti-dsDNA autoantibody in systemic lupus erythematosus patients without secondary Sjogren syndrome

PubMed Central

Chen, Alexander; Chen, Hung-Ta; Hwang, Yih-Hsiou; Chen, Yi-Tsun; Hsiao, Ching-Hsi; Chen, Hung-Chi

2016-01-01

Abstract There are as many as one-third of the systemic lupus erythematosus (SLE) patients who suffer from dry eye syndrome. To this date, dry eye syndrome in SLE patients is believed to be caused by secondary Sjogren syndrome (sSS). However, there is increasing evidence for possible independency of dry eye syndrome and sSS in patients suffering from autoimmune diseases. The purpose of this retrospective observational case series was to identify SLE patients without sSS who had dry eye syndrome, examine the correlation of different autoantibodies and dry eye severity, and determine the cause of dry eye in these patients. We included 49 consecutive SLE patients with dry eye who visited our dry eye clinic. In order to rule out sSS, these patients were all negative for anti-Sjogren's-syndrome-related antigen A and B (anti-SSA/SSB) and had no oral symptoms. Each patient's lupus activity was determined by serological tests including antidouble-stranded DNA antibody (anti-dsDNA), complement levels (C3, C4), erythrocyte sedimentation rate (ESR), and antinuclear antibody (ANA). Severity of dry eye syndrome was determined by corneal sensation (KSen), superficial punctuate keratopathy (SPK), Schirmer-I test (Schirmer), and tear film break-up time (TBUT). The autoantibodies and the dry eye parameters in each group were tested using the χ2 test or the Mann–Whitney U test for normally distributed or skewed data, respectively. The anti-dsDNA showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.042) but not TBUT. The C3 showed significant correlations with KSen (P < 0.001), SPK (P < 0.001), and Schirmer (P = 0.014) but not TBUT. No correlations of dry eye parameters were observed between C4, ESR, and ANA. The major finding of this study was that the severity of dry eye syndrome in SLE patients without sSS was strongly correlated with anti-dsDNA and C3 but not with C4, ESR, and ANA. PMID:27428227

N-Acetylcysteine protects against trichloroethene-mediated autoimmunity by attenuating oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Gangduo; Wang, Jianling; Ma, Huaxian

Exposure to trichloroethene (TCE), a ubiquitous environmental contaminant, is known to induce autoimmunity both in humans and animal models. However, mechanisms underlying TCE-mediated autoimmunity remain largely unknown. Previous studies from our laboratory in MRL +/+ mice suggest that oxidative stress may contribute to TCE-induced autoimmune response. The current study was undertaken to further assess the role of oxidative stress in TCE-induced autoimmunity by supplementing with an antioxidant N-acetylcysteine (NAC). Groups of female MRL +/+ mice were given TCE, NAC or TCE + NAC for 6 weeks (TCE, 10 mmol/kg, i.p., every 4th day; NAC, 250 mg/kg/day through drinking water). TCEmore » exposure led to significant increases in serum levels of anti-nuclear, anti-dsDNA and anti-Sm antibodies. TCE exposure also led to significant induction of anti-malondiadelhyde (MDA)- and anti-hydroxynonenal (HNE)-protein adduct antibodies which were associated with increased ANA in the sera along with increased MDA-/HNE-protein adducts in the livers and kidneys, and increases in protein oxidation (carbonylation) in the sera, livers and kidneys, suggesting an overall increase in oxidative stress. Moreover, TCE exposure also resulted in increased release of IL-17 from splenocytes and increases in IL-17 mRNA expression. Remarkably, NAC supplementation attenuated not only the TCE-induced oxidative stress, IL-17 release and mRNA expression, but also the markers of autoimmunity, as evident from decreased levels of ANA, anti-dsDNA and anti-Sm antibodies in the sera. These results provide further support to a role of oxidative stress in TCE-induced autoimmune response. Attenuation of TCE-induced autoimmunity in mice by NAC provides an approach for preventive and/or therapeutic strategies. - Highlights: • TCE led to increased autoantibodies, supporting its potential to induce autoimmunity. • TCE exposure led to increases in lipid perioxidation and protein carbonyls. • TCE exposure resulted in increased IL-17 release and in IL-17 mRNA expression. • NAC supplementation attenuated both TCE-induced oxidative stress and autoimmunity. • The findings further support a role of oxidative stress in TCE-induced autoimmunity.« less

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium.

PubMed

Brito-Zerón, Pilar; Acar-Denizli, Nihan; Zeher, Margit; Rasmussen, Astrid; Seror, Raphaele; Theander, Elke; Li, Xiaomei; Baldini, Chiara; Gottenberg, Jacques-Eric; Danda, Debashish; Quartuccio, Luca; Priori, Roberta; Hernandez-Molina, Gabriela; Kruize, Aike A; Valim, Valeria; Kvarnstrom, Marika; Sene, Damien; Gerli, Roberto; Praprotnik, Sonja; Isenberg, David; Solans, Roser; Rischmueller, Maureen; Kwok, Seung-Ki; Nordmark, Gunnel; Suzuki, Yasunori; Giacomelli, Roberto; Devauchelle-Pensec, Valerie; Bombardieri, Michele; Hofauer, Benedikt; Bootsma, Hendrika; Brun, Johan G; Fraile, Guadalupe; Carsons, Steven E; Gheita, Tamer A; Morel, Jacques; Vollenveider, Cristina; Atzeni, Fabiola; Retamozo, Soledad; Horvath, Ildiko Fanny; Sivils, Kathy; Mandl, Thomas; Sandhya, Pulukool; De Vita, Salvatore; Sanchez-Guerrero, Jorge; van der Heijden, Eefje; Trevisani, Virginia Fernandes Moça; Wahren-Herlenius, Marie; Mariette, Xavier; Ramos-Casals, Manuel

2017-06-01

To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis. The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating. Multivariable logistic regression analyses were performed. We included 7748 women (93%) and 562 men (7%), with a mean age at diagnosis of primary SjS of 53 years. Ethnicity data were available for 7884 patients (95%): 6174 patients (78%) were white, 1066 patients (14%) were Asian, 393 patients (5%) were Hispanic, 104 patients (1%) were black/African-American and 147 patients (2%) were of other ethnicities. SjS was diagnosed a mean of 7 years earlier in black/African-American compared with white patients; the female-to-male ratio was highest in Asian patients (27:1) and lowest in black/African-American patients (7:1); the prevalence of sicca symptoms was lowest in Asian patients; a higher frequency of positive salivary biopsy was found in Hispanic and white patients. A north-south gradient was found with respect to a lower frequency of ocular involvement in northern countries for dry eyes and abnormal ocular tests in Europe (OR 0.46 and 0.44, respectively) and Asia (OR 0.18 and 0.49, respectively) compared with southern countries. Higher frequencies of antinuclear antibodies (ANAs) were reported in northern countries in America (OR=1.48) and Asia (OR=3.80) while, in Europe, northern countries had lowest frequencies of ANAs (OR=0.67) and Ro/La (OR=0.69). This study provides the first evidence of a strong influence of geolocation and ethnicity on the phenotype of primary SjS at diagnosis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

HLW Return from France to Germany - 15 Years of Experience in Public Acceptance and Technical Aspects - 12149

DOE Office of Scientific and Technical Information (OSTI.GOV)

Graf, Wilhelm

Since in 1984 the national reprocessing concept was abandoned the reprocessing abroad was the only existing disposal route until 1994. With the amendment of the Atomic Energy Act in 2001 spent fuel management changed completely since from 1 June 2005 any delivery of spent fuel to reprocessing plants was prohibited and the direct disposal of spent fuel became mandatory. Until 2005 the total amount of spent fuel to be reprocessed abroad added up to 6080 t HM, 5309 t HM thereof in France. The waste generated from reprocessing - alternatively an equivalent amount of radioactive material - has to bemore » returned to the country of origin according to the commercial contracts signed between the German utilities and COGEMA, now AREVA NC, in France and BNFL, now INS in UK. In addition the German and the French government exchanged notes with the obligation of both sides to enable and support the return of reprocessing residues or equivalents to Germany. The return of high active vitrified waste from La Hague to the interim storage facility at Gorleben was demanding from the technical view i. e. the cask design and the transport. Unfortunately the Gorleben area served as a target for nuclear opponents from the first transport in 1996 to the latest one in 2011. The protection against sabotage of the railway lines and mass protests needed highly improved security measures. In France and Germany special working forces and projects have been set up to cope with this extraordinary situation. A complex transport organization was established to involve all parties in line with the German and French requirements during transport. The last transport of vitrified residues from France has been completed successfully so far thus confirming the efficiency of the applied measures. Over 15 years there was and still is worldwide no comparable situation it is still unique. Summing up, the exceptional project handling challenge that resulted from the continuous anti-nuclear civil disobedience in Germany over the whole 15-year long project running time could be faced efficiently. It has to be concluded that despite of all problems the anti-nuclear activities have caused so far, all transports of vitrified HLW have always been completed successfully by adapting the commonly established safety, security and public acceptance measures to the special conditions and needs in Germany and coordinating the activities of all parties involved but at the expense of high costs for industry and government and a challenging operational complexity. Apart from an anticipatory project planning a good communication between all involved industrial parties and the French and the German government was the key to the effective management of such shipments and to minimize the radiological, economic, environmental, public and political impact. The future will show how efficiently the gained experience can be used for further return projects which are to be realized since no reprocessed waste has yet been returned from UK and neither the medium-level nor the low-level radioactive waste has been transferred from France to Germany. (author)« less

Using the American College of Rheumatology (ACR) and Systemic Lupus International Collaborating Clinics (SLICC) criteria to determine the diagnosis of systemic lupus erythematosus (SLE) in patients with subacute cutaneous lupus erythematosus (SCLE).

PubMed

Tiao, Janice; Feng, Rui; Carr, Kasey; Okawa, Joyce; Werth, Victoria P

2016-05-01

Approximately 50% of patients with subacute cutaneous lupus erythematosus (SCLE) meet criteria for systemic lupus erythematosus (SLE). The Systemic Lupus International Collaborating Clinics (SLICC) developed new SLE criteria to improve the American College of Rheumatology (ACR) criteria but the SLICC criteria have not been evaluated in patients with SCLE. We sought to determine how patients with SCLE/SLE meet the ACR and SLICC criteria to compare the 2 sets of criteria. This was a retrospective analysis of 107 patients with SCLE enrolled in a database at the University of Pennsylvania. Patients with SCLE/SLE were more likely than those with only SCLE to have oral ulcers, positive anti-double-stranded DNA antibodies, and positive antinuclear antibody test findings using both sets of criteria. Patients with SCLE/SLE were also more likely to have low complement using the SLICC criteria. There was a statistically insignificant increase in individuals meeting the SLICC criteria. Not all patients received comprehensive laboratory testing. Most patients with SCLE who formally meet criteria for SLE do so based on the laboratory and mucocutaneous criteria. Neither the ACR nor SLICC criteria distinguish patients with SCLE and major internal disease from patients with SCLE without major internal disease. Published by Elsevier Inc.

[Childhood-onset systemic polyarteritis nodosa and systemic lupus erythematosus: an overlap syndrome?

PubMed

Marques, Victor L S; Guariento, Andressa; Simões, Marlise S M; Blay, Gabriela; Lotito, Ana Paola N; Silva, Clovis A

2015-03-04

We described herein a patient who presented an overlap syndrome of childhood-onset systemic polyarteritis nodosa (c-PAN) and childhood-onset systemic lupus erythematosus (c-SLE). A 9-year-old girl presented tender subcutaneous nodules on feet, arterial hypertension, right hemiplegia and dysarthric speech. She was hospitalized due to stroke and left foot drop. Brain computer tomography showed ischemic stroke. Magnetic resonance angiography revealed stenosis in the middle cerebral and internal carotid arteries. Electroneuromyography identified a mononeuropathy of left posterior tibial nerve and she fulfilled the c-PAN validated criteria. She was treated with intravenous methylprednisolone pulse therapy followed by prednisone, that was progressively tapered, six months of intravenous cyclophosphamide and after that she received azathioprine for 19 months. At the age of 14 years and 9 months, she presented malar rash, photosensitivity, edema in lower limbs and arterial hypertension. The proteinuria was 1.7g/day. Antinuclear antibodies (ANA) were 1/1280 (homogeneous nuclear pattern) and anti-dsDNA antibodies were positive. Renal biopsy showed focal proliferative and membranous glomerulonephritis. Therefore, she fulfilled the American College of Rheumatology classification criteria for SLE and she was treated with prednisone, hydroxychloroquine and mycophenolate mofetil. In conclusion, we described herein a possible overlap syndrome of two autoimmune diseases, where c-PAN occurred five years before the c-SLE diagnosis. Copyright © 2015 Elsevier Editora Ltda. All rights reserved.

Defective B cell response to T-dependent immunization in lupus-prone mice

PubMed Central

Niu, Haitao; Sobel, Eric S.; Morel, Laurence

2009-01-01

Lupus anti-nuclear Abs show the characteristics of Ag-driven T cell-dependent (TD) humoral responses. If autoAgs elicit the same response as exogenous Ags, lupus should enhance humoral responses to immunization. Blunted responses to various immunizations have, however, been reported in a significant portion of lupus patients. In this study, we show that lupus-prone B6.Sle1.Sle2.Sle3 (B6.TC) mice produce significantly less Ab in response to TD immunization than congenic controls, while producing significantly more total Ig. This blunted Ab response to TD Ag could be reconstituted with B6.TC B and CD4+ T cells. Multiple defects were found in the B6.TC response to NP-KLH as compared to total Ig, including a smaller percentage of B cells participating to the NP-response, a reduced entry into germinal centers, and highly defective production of NP-specific long-lived plasma cells in the bone marrow. B6.TC plasma cells expressed reduced levels of FcγRIIb, which suggests that reduced apoptosis in resident plasma cells prevents the establishment of newly-formed NP-specific plasma cells in bone marrow niches. Overall, these results show that lupus-prone mice responded differently to auto- and exogenous antigens and suggest that low FcγRIIb, hypergammaglobulinemia and high autoantibody production would be predictive of a poor response to immunization in lupus patients. PMID:18924209

Development of Murine Lupus Involves the Combined Genetic Contribution of the SLAM and FcγR Intervals within the Nba2 Autoimmune Susceptibility Locus

PubMed Central

Jørgensen, Trine N.; Alfaro, Jennifer; Enriquez, Hilda L.; Jiang, Chao; Loo, William M.; Atencio, Stephanie; Bupp, Melanie R. Gubbels; Mailloux, Christina M.; Metzger, Troy; Flannery, Shannon; Rozzo, Stephen J.; Kotzin, Brian L.; Rosemblatt, Mario; Bono, María Rosa; Erickson, Loren D.

2010-01-01

Autoantibodies are of central importance in the pathogenesis of Ab-mediated autoimmune disorders. The murine lupus susceptibility locus Nba2 on chromosome 1 and the syntenic human locus are associated with a loss of immune tolerance that leads to antinuclear Ab production. To identify gene intervals within Nba2 that control the development of autoantibody-producing B cells and to determine the cellular components through which Nba2 genes accomplish this, we generated congenic mice expressing various Nba2 intervals where genes for the FcγR, SLAM, and IFN-inducible families are encoded. Analysis of congenic strains demonstrated that the FcγR and SLAM intervals independently controlled the severity of autoantibody production and renal disease, yet are both required for lupus susceptibility. Deregulated homeostasis of terminally differentiated B cells was found to be controlled by the FcγR interval where FcγRIIb-mediated apoptosis of germinal center B cells and plasma cells was impaired. Increased numbers of activated plasmacytoid dendritic cells that were distinctly CD19+ and promoted plasma cell differentiation via the proinflammatory cytokines IL-10 and IFNα were linked to the SLAM interval. These findings suggest that SLAM and FcγR intervals act cooperatively to influence the clinical course of disease through supporting the differentiation and survival of autoantibody-producing cells. PMID:20018631

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP): An Uncommon Manifestation of Systemic Lupus Erythematosus (SLE)

PubMed Central

Abraham, Hrudya; Kuzhively, Jose; Rizvi, Syed W.

2017-01-01

Patient: Female, 40 Final Diagnosis: Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) Symptoms: Gait disorder Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare disease Background: Chronic inflammatory demyelinating polyneuropathy (CIDP) is an uncommon manifestation of systemic lupus erythematosus (SLE). We report a case of SLE presenting as CIDP and discuss the diagnosis, management, and prognosis of CIDP. Case Report: A 40-year-old woman with a past medical history of SLE treated with hydroxychloroquine presented with bilateral, progressive, ascending, sensory and motor neuropathy. Physical examination showed weakness and reduced temperature of all extremities, reduced pinprick and vibration sense of the distal extremities, loss of reflexes, and walking with a wide-based unsteady gait. Laboratory investigations showed positive antinuclear antibodies (ANA), anti-(smooth muscle (SM) antibody, anti-RNP antibody, anti-SSA antibody, anti-ds-DNA antibody, and an erythrocyte sedimentation rate (ESR) of 75 mm/hr, low C4, leukopenia, and anemia. Electromyography (EMG) confirmed the diagnosis of CIDP. The patient’s neuropathy and muscle weakness improved on treatment with intravenous immunoglobulin (IVIG) and high-dose steroids. Conclusions: The early clinical diagnosis of CIDP, supported by serological autoantibody profiles associated with SLE, can predict a good response to steroids. Most patients with CIDP are treated successfully with steroids if the diagnosis is made early. IVIG, plasmapheresis, or immunosuppressive therapy should be considered if there is no response to steroids. PMID:28894082

Antigen Specific Responses and ANA production in B6.Sle1b mice: A role for SAP

PubMed Central

Jennings, Paula; Chan, Alice; Schwartzberg, Pamela; Wakeland, Edward K.; Yuan, Dorothy

2010-01-01

B6.Sle1b mice, which contain the Sle1b gene interval derived from lupus prone NZM2410 mice on a C57BL/6 background, present with gender-biased, highly penetrant anti-nuclear antibody (ANA) production. To obtain some insight into the possible induction mechanism of autoantibodies in these mice we compared antigen specific T dependent (TD) and T independent (TI-II) responses between B6.Sle1b and B6 mice before the development of high ANA titers. Our results show that B6.Sle1b mice mount enhanced responses to a TI-II antigen. Additionally, the memory T cell response generated by a TD antigen was also increased. This enhancement correlates with the greater ability of B cells from B6.Sle1b mice to present antigen to T cells. The SLAM Associated Protein (SAP) is critical for signaling of many of the molecules encoded by the SLAM/CD2 gene cluster, candidates for mediating the Sle1b phenotype; therefore, we also investigated the effect of sap deletion in these strains on the TD and TI-II responses as well as on ANA production. The results of these studies of responses to non-self antigens provide further insight for the mechanism by which responses to self-antigens might be initiated in the context of specific genetic alterations. PMID:18845419

Borrelia Lymphocytoma Mimicking Butterfly Rash in a Pediatric Patient.

PubMed

Llamas-Velasco, Mar; Paredes, Bruno Emilio

2018-03-01

A 5-year-old girl presented with a facial butterfly rash that persisted for 5 months without arthralgia, fever, malaise, photosensitivity, or other symptoms. Lupus erythematosus was clinically suspected. All blood tests were negative or within normal values. Skin biopsy showed a dense nodular superficial and deep inflammatory infiltrate of lymphocytes that reaches subcutaneous tissue. The most striking histopathological finding was plasma cells with some perifollicular accentuation. Borrelia polymerase chain reaction assay of the tissue was positive, and we made the diagnoses of borrelia lymphocytoma mimicking butterfly rash of lupus erythematosus. The lesions disappeared with amoxicillin followed by cefuroxime for 28 days. In children, a variety of diseases including lupus erythematous may lead to a butterfly rash that is usually short lasting and commonly associated with systemic symptoms. Borreliosis may be related with long-lasting facial erythema in children and may mimic lupus and present high titers of antinuclear antibodies. In any case, borrelial lymphocytoma has not been previously reported as a cause of butterfly rash, thus mimicking acute lupus in a child, as in our case. From a histopathological point of view, the presence of plasma cells in a pseudolymphomatous infiltrate is a clue for the right diagnosis. Therefore, we suggest that borrelia serology should be done in children with butterfly rash lasting more than a month and empirical antibiotic treatment should be tried even in cases with negative serology.

Hypothyroidism in patients with autoimmune pancreatitis.

PubMed

Shimizuguchi, Ryoko; Kamisawa, Terumi; Endo, Yuka; Kikuyama, Masataka; Kuruma, Sawako; Chiba, Kazuro; Tabata, Taku; Koizumi, Satomi

2018-05-06

To examine thyroid function and clinical features of hypothyroidism in autoimmune pancreatitis (AIP) patients. We examined thyroid function in 77 patients with type 1 AIP (50 males, 27 females; median age 68 years, range 33-85) diagnosed according to the Japanese diagnostic criteria for AIP 2011. We compared clinical and serological findings between patients with and without various categories of hypothyroidism. The change in hypothyroidism after steroid therapy was also examined. Eight patients (10%) had hypothyroidism of 6 patients had subclinical hypothyroidism with a normal serum free thyroxine (FT4) and high thyroid stimulating hormone (TSH) level, and 2 patients had central hypothyroidism with low serum free triiodothyronine (FT3), FT4 and TSH levels. A significant goiter of the thyroid was not observed in any patient. There were no significant differences in age; male to female ratio; serum concentrations of IgG and IgG4-related disease (IgG4-RD); presence of anti-thyroglobulin antibody, antinuclear antigen or rheumatoid factor; or presence of extrapancreatic lesions between the 6 patients with subclinical hypothyroidism and patients with euthyroidism. After steroid therapy, both subclinical and central hypothyroidism improved with improvement of the AIP. Hypothyroidism was observed in 8 (10%) of 77 AIP patients and was subclinical in 6 patients and central in 2 patients. Further studies are necessary to clarify whether this subclinical hypothyroidism is another manifestation of IgG4-RD.

Btk levels set the threshold for B-cell activation and negative selection of autoreactive B cells in mice.

PubMed

Kil, Laurens P; de Bruijn, Marjolein J W; van Nimwegen, Menno; Corneth, Odilia B J; van Hamburg, Jan Piet; Dingjan, Gemma M; Thaiss, Friedrich; Rimmelzwaan, Guus F; Elewaut, Dirk; Delsing, Dianne; van Loo, Pieter Fokko; Hendriks, Rudi W

2012-04-19

On antigen binding by the B-cell receptor (BCR), B cells up-regulate protein expression of the key downstream signaling molecule Bruton tyrosine kinase (Btk), but the effects of Btk up-regulation on B-cell function are unknown. Here, we show that transgenic mice overexpressing Btk specifically in B cells spontaneously formed germinal centers and manifested increased plasma cell numbers, leading to antinuclear autoantibody production and systemic lupus erythematosus (SLE)-like autoimmune pathology affecting kidneys, lungs, and salivary glands. Autoimmunity was fully dependent on Btk kinase activity, because Btk inhibitor treatment (PCI-32765) could normalize B-cell activation and differentiation, and because autoantibodies were absent in Btk transgenic mice overexpressing a kinase inactive Btk mutant. B cells overexpressing wild-type Btk were selectively hyperresponsive to BCR stimulation and showed enhanced Ca(2+) influx, nuclear factor (NF)-κB activation, resistance to Fas-mediated apoptosis, and defective elimination of selfreactive B cells in vivo. These findings unravel a crucial role for Btk in setting the threshold for B-cell activation and counterselection of autoreactive B cells, making Btk an attractive therapeutic target in systemic autoimmune disease such as SLE. The finding of in vivo pathology associated with Btk overexpression may have important implications for the development of gene therapy strategies for X-linked agammaglobulinemia, the immunodeficiency associated with mutations in BTK.

New-onset systemic lupus erythematosus in a long-term hemodialysis patient with acute pleuritis and pneumonitis.

PubMed

Hiyamuta, Hiroto; Yamada, Shunsuke; Yotsueda, Ryusuke; Hasegawa, Shoko; Nakano, Toshiaki; Taniguchi, Masatomo; Tsukamoto, Hiroshi; Kitazono, Takanari; Tsuruya, Kazuhiko

2015-11-01

A 61-year-old woman, with a 25-year history of maintenance hemodialysis due to end-stage renal disease of unknown causes, was admitted because of systemic joint pain and inflammatory response of unknown etiology that persisted for 1 month. Laboratory data on admission revealed leukocytopenia, lymphocytopenia, high serum C-reactive protein, and positivity for antinuclear antibody (ANA) and anti-double strand DNA. After admission, she progressively developed cough and dyspnea. A chest radiograph revealed bilateral ground glass opacity and pleural effusion. A thoracentesis revealed lupus erythematosus cells, suggesting lupus pleuritis. A chest computed tomography showed a pattern of diffuse alveolar damage compatible with acute lupus pneumonitis. She fulfilled the American Rheumatism Association diagnostic criteria for systemic lupus erythematosus (SLE). Methylprednisolone pulse therapy followed by oral prednisone treatment improved the clinical symptoms and laboratory abnormalities. ANA was negative 25 years earlier when she first started hemodialysis and she had neither clinical nor serological abnormalities related to SLE during the last 25 years. Further, she had neither received drugs that can cause drug-induced SLE, nor had a history of ultraviolet ray exposure, pregnancy, blood transfusion, trauma and smoking. This report suggests that new-onset SLE can develop in patients undergoing long-term dialysis. Hence, when we encounter dialysis patients with arthralgia and/or respiratory disorders, we should consider the possibility of new-onset SLE.

[LE cells in synovial fluid: prevalence and diagnostic usefulness in rheumatic diseases].

PubMed

Puszczewicz, Mariusz; Białkowska-Puszczewicz, Grazyna

2010-01-01

This study was undertaken to determine the prevalence of LE cells in synovial fluid and their importance for the diagnosis of rheumatic disease. Synovial fluid was obtained from 631 patients: 31 with systemic lupus erythematosus (SLE), 337 with rheumatoid arthritis (RA), 4 with Still's disease, 9 with systemic scleroderma (SS), 27 with the overlap syndrome (RA/SLE), 132 with ankylosing spondylitis (AS), 57 with Reiter's syndrome, and 34 with psoriatic arthritis (PA). The fluid was centrifuged, precipitate smears were done and were May-Grünwald-Giemsa stained for cytologic assessment. The supernatant was collected for antinuclear antibody (ANA) testing. Physicochemical and serologic properties of the synovial fluid were routinely determined. All synovial fluids demonstrated signs of inflammation. The presence of LE cells was ascertained in five patients with SLE and nine patients with the overlap syndrome. In these cases, LE cells were accompanied by ANA. In addition, hematoxylin bodies were revealed in SLE patients. LE cells were observed in 2.6% of patients with RA but were not accompanied by ANA. Patients with SS, Still's disease, AS, Reiter's syndrome, and PA tested negative for LE cells. It appears from these results that LE cells are rarely present in the synovial fluid of patients with rheumatic diseases. In contrast, they occur in more than 40% of patients with the overlap syndrome and may thus be regarded as important for the diagnosis of this condition.

An unusual presenting symptom of graves' disease: myalgia.

PubMed

Papanikolaou, N; Perros, P

2013-01-01

A 50-year-old female patient presented with severe myalgia involving her proximal muscles for 3-4 weeks. She also reported mild thyrotoxic symptoms over the same time period. Examination revealed mild thyrotoxicosis, a moderate diffuse goiter and no eye signs. The clinical picture was dominated by muscle pain and tenderness involving mainly her proximal arms and legs, her calves and her fingers, requiring opiate analgesia. Muscle power and tendon reflexes were normal. Laboratory evaluation revealed undetectable serum thyroid stimulating hormone (TSH) with raised FT4, FT3 and positive TSH receptor antibodies. Treatment with carbimazole was started. Additional laboratory investigations were negative (inflammatory markers, creatine kinase and antibodies to antinuclear antibodies, gastric parietal cell, smooth muscle, mitochondrial, dsDNA, centromere, extractable nuclear antigen (ENA) ribonucleoprotein, ENA Sm, ENA Ro, ENA Anti-La, ENA Scl70, ENA Jo-1, anti-CCP and rheumatoid factor). Further assessment in the rheumatology clinic confirmed there was no small joint tenderness or loss of range of movement of her limbs, but widespread and profound muscle tenderness of the common extensors of the forearms, biceps, trapezius, calves and thighs. She was treated symptomatically with analgesic medication and continued on carbimazole. A month later she was euthyroid and her myalgia had resolved. Hyperthyroidism has a profound effect on skeletal muscle and often leads to myopathy. Severe myalgia in association with Graves' disease is rare and resolves with the restoration of euthyroidism.

Schistosome Infection Intensity Is Inversely Related to Auto-Reactive Antibody Levels

PubMed Central

Mutapi, Francisca; Imai, Natsuko; Nausch, Norman; Bourke, Claire D.; Rujeni, Nadine; Mitchell, Kate M.; Midzi, Nicholas; Woolhouse, Mark E. J.; Maizels, Rick M.; Mduluza, Takafira

2011-01-01

In animal experimental models, parasitic helminth infections can protect the host from auto-immune diseases. We conducted a population-scale human study investigating the relationship between helminth parasitism and auto-reactive antibodies and the subsequent effect of anti-helminthic treatment on this relationship. Levels of antinuclear antibodies (ANA) and plasma IL-10 were measured by enzyme linked immunosorbent assay in 613 Zimbabweans (aged 2–86 years) naturally exposed to the blood fluke Schistosoma haematobium. ANA levels were related to schistosome infection intensity and systemic IL-10 levels. All participants were offered treatment with the anti-helminthic drug praziquantel and 102 treated schoolchildren (5–16 years) were followed up 6 months post-antihelminthic treatment. ANA levels were inversely associated with current infection intensity but were independent of host age, sex and HIV status. Furthermore, after allowing for the confounding effects of schistosome infection intensity, ANA levels were inversely associated with systemic levels of IL-10. ANA levels increased significantly 6 months after anti-helminthic treatment. Our study shows that ANA levels are attenuated in helminth-infected humans and that anti-helminthic treatment of helminth-infected people can significantly increase ANA levels. The implications of these findings are relevant for understanding both the aetiology of immune disorders mediated by auto-reactive antibodies and in predicting the long-term consequences of large-scale schistosomiasis control programs. PMID:21573157

Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus

PubMed Central

Rodgers, D T; Pineda, M A; Suckling, C J; Harnett, W

2015-01-01

Introduction ES-62, a phosphorylcholine (PC)-containing immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, protects against nephritis in the MRL/Lpr mouse model of systemic lupus erythematosus (SLE). However, ES-62 is not suitable for development as a therapy and thus we have designed drug-like small molecule analogues (SMAs) based around its active PC-moiety. To provide proof of concept that ES-62-based SMAs exhibit therapeutic potential in SLE, we have investigated the capacity of two SMAs to protect against nephritis when administered to MRL/Lpr mice after onset of kidney damage. Methods SMAs 11a and 12b were evaluated for their ability to suppress antinuclear antibody (ANA) generation and consequent kidney pathology in MRL/Lpr mice when administered after the onset of proteinuria. Results SMAs 11a and 12b suppressed development of ANA and proteinuria. Protection reflected downregulation of MyD88 expression by kidney cells and this was associated with reduced production of IL-6, a cytokine that exhibits promise as a therapeutic target for this condition. Conclusions SMAs 11a and 12b provide proof of principle that synthetic compounds based on the safe immunomodulatory mechanisms of parasitic worms can exhibit therapeutic potential as a novel class of drugs for SLE, a disease for which current therapies remain inadequate. PMID:26085597

[Generalized tendomyopathy (fibromyalgia): differential diagnosis, therapy and prognosis].

PubMed

Schmidt, K L

1991-08-01

The generalised tendomyopathy is one of the most variegated and fascinating disease of man. The unusual constellation and combination of symptoms constrain to the differential-diagnostic demarcation of a great number of rheumatic and non-rheumatic diseases. While the rheumatic polymyalgia and myositis are easily to be demarcated, the decision between a primary and secondary generalised tendomyopathy can be difficult. In individual cases a classical tendomyopathy can be accompanied by antinuclear factors and then it is at the earliest a "collagenosis the state of waiting". The therapy of tendomyopathy is altogether unsatisfactory. All forms of therapy (medicamentous, physical, psychotherapy) help at the utmost in 50%. Surprisingly, on the part of the medicaments the non-steroidal antiphlogistic drugs and the glucocorticoids in most cases completely fail, and also the physical therapy is frequently not tolerated and/or has only a short duration of effect. The more important are the influence on possible evoking factors, the optimization of the social background and the utilization of the possibilities of the "secondary prevention" (balneotherapy in a health resort, sauna bath, Kneipp's applications, change of the living and working conditions, easy sports activities). Since the disease is frequent, but not yet known in general, it should be made better acquainted among the physicians. The generalised tendomyopathy is and remains a cardinal problem not only of rheumatology, but of the physician's working-day in general.

Clinical and laboratory features of systemic sclerosis complicated with localized scleroderma.

PubMed

Toki, Sayaka; Motegi, Sei-ichiro; Yamada, Kazuya; Uchiyama, Akihiko; Kanai, Sahori; Yamanaka, Masayoshi; Ishikawa, Osamu

2015-03-01

Localized scleroderma (LSc) primarily affects skin, whereas systemic sclerosis (SSc) affects skin and various internal organs. LSc and SSc are considered to be basically different diseases, and there is no transition between them. However, LSc and SSc have several common characteristics, including endothelial cell dysfunction, immune activation, and excess fibrosis of the skin, and there exist several SSc cases complicated with LSc during the course of SSc. Clinical and laboratory characteristics of SSc patients with LSc remain unclear. We investigated the clinical and laboratory features of 8 SSc patients with LSc among 220 SSc patients (3.6%). The types of LSc included plaque (5/8), guttate (2/8), and linear type (1/8). All cases were diagnosed as having SSc within 5 years before or after the appearance of LSc. In three cases of SSc with LSc (37.5%), LSc skin lesions preceded clinical symptoms of SSc. Young age, negative antinuclear antibody, and positive anti-RNA polymerase III antibody were significantly prevalent in SSc patients with LSc. The positivity of anticentromere antibody tended to be prevalent in SSc patients without LSc. No significant difference in the frequency of complications, such as interstitial lung disease, reflux esophagitis, and pulmonary artery hypertension, was observed. The awareness of these characteristic of SSc with LSc are essential to establish an early diagnosis and treatment. © 2015 Japanese Dermatological Association.

Strain difference in the immune response to hydralazine in inbred guinea-pigs

PubMed Central

Ellman, L.; Inman, J.; Green, Ira

1971-01-01

Guinea-pigs were immunized with hydralazine in Freund's complete adjuvant. A marked strain difference in the immune response involving both anti-hydralazine antibody and delayed hypersensitivity to hydralazine was observed in different strains of guinea-pigs: Hartley guinea-pigs and inbred strain 13 guinea-pigs were able to mount a vigorous immune response to the drug while inbred strain 2 guinea-pigs appeared to be `low or non-responders'. This difference could not be explained in terms of metabolism of the drug in that no differences in acetylation were observed. Breeding studies suggest that immune responsiveness to hydralazine is inherited in an autosomal dominant manner. The immune response to hydralazine may be controlled by a `specific immune response gene' which appears not to be linked to the major strain 13 histocompatibility gene. Anti-nuclear and anti-DNA antibodies could not be demonstrated at a time when the animals manifested a strong immune response to hydralazine. Thus, the development of auto-immune phenomena does not appear to be related to the development of an immune response to the drug in short term immunization. Hydralazine-protein conjugates were synthesized, radio-iodinated and used in a Farr technique for the measurement of anti-hydralazine antibody. These techniques for the assay of anti-hydralazine antibodies may be useful in clinical investigations. Imagesp933-a PMID:5316639

Progressive respiratory distress in a 42-year-old HIV-positive woman with systemic lupus erythematosus.

PubMed

Mutengo, Katongo; Mukomena, Patrice; Lambwe, Nason; Ngalamika, Owen

2017-06-17

Identifying and treating the cause of pulmonary symptoms in HIV patients with underlying systemic lupus erythematosus (SLE) can be very challenging. Delays in diagnosing active SLE in HIV patients can lead to significant morbidity and even mortality. We report the case of an HIV-positive woman with SLE who presented with severe respiratory distress. A 42-year-old HIV-positive woman presented with a 7-month history of anorexia, progressive dyspnoea, and a productive cough. She had been put on treatment for pulmonary tuberculosis and pneumocystis jiroveci pneumonia for several months by the referring hospital without any significant improvement in her symptoms. Her initial laboratory investigations showed highly elevated d-dimer test results but confirmatory investigations for pulmonary embolism proved otherwise. An autoimmune screen revealed highly positive antinuclear antibody and anti-double-stranded DNA tests, and she responded very well to SLE treatment. Our case represents a situation where two diseases with antagonizing pathways of disease pathogenesis occur concurrently in the same patient. SLE is usually not among the differential diagnoses in HIV patients with respiratory distress. Management of patients with both SLE and HIV is also very challenging because improvement in one condition can lead to worsening of the other. Despite opportunistic infections being the likely cause of pulmonary symptoms in HIV patients, clinicians are encouraged to have a high index of suspicion for autoimmune interstitial lung disease in these patients.

A 3-Year-Old Girl with Recurrent Infections and Autoimmunity due to a STAT1 Gain-of-Function Mutation: The Expanding Clinical Presentation of Primary Immunodeficiencies.

PubMed

Aldave Becerra, Juan Carlos; Cachay Rojas, Enrique

2017-01-01

We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs. At 2.5 years of age, she was admitted with lupus-like syndrome, including serositis, hemolytic anemia, thrombocytopenia, and positive antinuclear (1:80) and dsDNA (1:10) autoantibodies. Available immunologic testing was not contributory. Imaging studies revealed bilateral ethmoidal sinusitis and mild hepatomegaly. Bone marrow analysis did not showed evidence of leukemia or myelodysplasia, while renal biopsy concluded mild mesangial proliferation. Genetic studies revealed a pathogenic heterozygous signal transducer and activator of transcription 1 gain-of-function mutation (WT/P293L). The clinical status and lung function of the patient has worsened progressively. She has not achieved an optimal response to therapy, including high-dose intravenous immunoglobulin, GM-CSF, prophylactic antibiotics and antifungal drugs, so we plan to perform hematopoietic stem cell transplantation.

Benign symmetric lipomatosis (Launois-Bensaude syndrome).

PubMed

Fernández-Vozmediano, José; Armario-Hita, José

2005-03-01

A 37-year-old woman with a personal history of appendicectomy, cholecystectomy, left oophorectomy secondary to an ovarian cyst complication, nephritic colic with repeated episodes of pyelonephritis, alcoholic hepatopathy, Raynaud's phenomenon and bilateral exophthalmos showed an increase in volume in the root of the upper limbs and in the base of the neck over a period of 4 years, painful to the touch and of a soft consistency. She presented with a pseudo-athletic appearance (Fig. 1) produced by an increase in the volume at the root of the upper limbs, upper back and the back of the neck (Fig. 2). The lesions produced a pulling sensation and were associated with paresthesia, hyperesthesia, and a moderate loss of strength in both arms. A biopsy taken from the upper third of the right arm showed a diffuse proliferation of the subcutaneous adipose tissue, which appeared normal, and extended between the collagen fibers, reaching in some cases into the most superficial zones of the reticular dermis (Fig. 3). Laboratory evaluation revealed a chronic anemia, leukopenia with moderate lymphopenia, increased erythrocyte sedimentation rate, elevation of enzymes of hepatic function, decrease in total proteins, and increase in ferritin, all in the context of hepatopathy. Antinuclear antibodies and the hormonal profile were normal. Abdominal and gynecologic echography revealed a right ovarian cyst of no clinical relevance. Cranial nuclear magnetic resonance (NMR) revealed an increase in the periorbital fat responsible for bilateral exophthalmos.

[Effective combination therapy of plasma exchange and subsequent cyclophosphamide pulses for catastrophic antiphospholipid antibody syndrome: a case report].

PubMed

Miyamae, T; Imagawa, T; Ito, S; Katakura, S; Mori, M; Ibe, M; Mitsuda, T; Aihara, Y; Nakanishi, S; Kohri, T; Yokota, S

1999-06-01

A 7-year-old girl with catastrophic antiphospholipid antibody syndrome was described. She firstly admitted to the local hospital with the complaints of persistent fever and abdominal pain, and was diagnosed as systemic lupus erythematosus with the laboratory findings as follows; positive for antinuclear antibody, anti-DNA antibody, and platelet-associated IgG, thrombocytopenia, and hypocomplementemia. 10 days after the initiation of oral prednisolone, she suddenly manifested tonic convulsion and unconsciousness accompanied by high fever. Because of the unresponsiveness to the methylprednisolone pulse therapy for supposed CNS lupus, she was transferred to our hospital. Her unconsciousness persisted, and pulsation on dorsalis pedis was not palpable on admission. Laboratory investigation revealed the falsely positive VDRL, a prolonged aPTT, positive for lupus-anticoagulant and antiphospholipid antibody. The magnetic resonance image demonstrated multiple spotty hyperintensity (T2) in the brain consistent with multiple hemorrhagic infarcts. Arteriogram demonstrated the infarct of dorsalis pedis, and coronary aneurysms. These findings were compatible with the criteria of catastrophic antiphospholipid antibody syndrome, she was diagnosed as catastrophic antiphospholipid antibody syndrome. The plasma exchange and subsequent cyclophosphamide-pulse therapy, which was given once a month for first 6 months, and later, at 3 months intervals, was effectively administered. This combination and oral anti-thrombotic therapy revealed effective for this kind of fatal disorder.

Asymptomatic macrothrombocytopenia in a young pure-bred beagle dog: a case report.

PubMed

Bodié, Karen; Gagne, Gerard D; Sramek, Mary K; Desmond, David J; Abel, Stephen J; Fagerland, Jane A

2011-10-01

During baseline evaluation prior to a preclinical safety study, a 10-month-old male pure-bred Beagle dog was found to have marked thrombocytopenia (6 × 10(3) platelets [PLT]/µL) associated with a mean platelet volume (MPV) of 17.9 fL. Tests for Rickettsia rickettsii, Ehrlichia canis, and Borrelia burgdorferi were negative. Buccal bleeding time was normal. Over 3 months, PLT were 4 to 141 × 10(3) PLT/µL, and MPV was 11.4 to 25.1 fL; however, PLT were <50 × 10(3) PLT/µL and MPV was >16 fL during most of this period. Antinuclear antibody (ANA) and anti-PLT antibody tests were negative. Genotyping for the presence of a beta 1-tubulin mutation demonstrated the normal wild-type gene. Treatment with prednisone resulted in normal values after only 3 days. Ultrastructure of enlarged PLT was consistent with that of immature PLT, characterized by reduced numbers of peripheral microtubules and the presence of rough endoplasmic reticulum, free ribosomes, Golgi apparatus, and a prominent canalicular system. PLT ultrastructure and glucocorticoid responsiveness supported a diagnosis of immune-mediated thrombocytopenia that was masked by the cyclic nature of PLT decreases and lack of clinical signs. Inclusion of such a dog in a preclinical safety study could result in misinterpretation of clinical pathology findings.

Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Yuehai; Cardiovascular Department, The Second Clinical Medical College of Fujian Medical University, Quanzhou, Fujian 362000; Lu, Huixia

Highlights: • Titers of ANA and anti-dsDNA antibodies were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • The spleen weights and glomerular areas were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • Expressions of IgG and C3 in glomeruli were similar in ApoE{sup −/−} and Fas{sup −/−} mice. • IgG, C3 and macrophage infiltration in aortic plaques were found in ApoE{sup −/−} mice. - Abstract: Background: Apolipoprotein E-knockout (ApoE{sup −/−}) mice is a classic model of atherosclerosis. We have found that ApoE{sup −/−} mice showed splenomegaly, higher titers of serum anti-nuclear antibody (ANA) and anti-dsDNA antibody compared withmore » C57B6/L (B6) mice. However, whether ApoE{sup −/−} mice show autoimmune injury remains unclear. Methods and results: Six females and six males in each group, ApoE{sup −/−}, Fas{sup −/−} and B6 mice, were used in this study. The titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein were measured by ELISA after 4 months of high-fat diet. The spleen weight and the glomerular area were determined. The expressions of IgG, C3 and macrophage in kidney and atherosclerotic plaque were detected by immunostaining followed by morphometric analysis. Similar to the characteristics of Fas{sup −/−} mice, a model of systemic lupus erythematosus (SLE), ApoE{sup −/−} mice, especially female, displayed significant increases of spleen weight and glomerular area when compared to B6 mice. Also, elevated titers of serum ANA, anti-dsDNA antibody and creatinine and urine protein. Moreover, the expressions of IgG, C3 and macrophage in glomeruli and aortic plaques were found in ApoE{sup −/−} mice. In addition, the IgG and C3 expressions in glomeruli and plaques significantly increased (or a trend of increase) in female ApoE{sup −/−} mice compared with males. Conclusions: Apolipoprotein E-knockout mice on high-fat diet show autoimmune injury on kidney and aorta.« less

Anti-inflammatory activities of Ganoderma lucidum (Lingzhi) and San-Miao-San supplements in MRL/lpr mice for the treatment of systemic lupus erythematosus.

PubMed

Cai, Zhe; Wong, Chun Kwok; Dong, Jie; Jiao, Delong; Chu, Man; Leung, Ping Chung; Lau, Clara Bik San; Lau, Ching Po; Tam, Lai Shan; Lam, Christopher Wai Kei

2016-01-01

Ganoderma lucidum (Lingzhi; LZ) and San-Miao-San (SMS) are Chinese medicines (CMs) used to treat inflammatory ailments and numbing syndrome/arthralgia syndrome (Bi Zheng), respectively. Given that the main symptoms of systemic lupus erythematosus (SLE) include inflammation of the joints, joint pain, edema and palpitations of the heart because of problems associated with Bi Zheng, it was envisaged that LZ and SMS could be used as potential treatments for this autoimmune disease. This study aims to investigate the anti-inflammatory activity of a combination formulation containing LZ and SMS (LZ-SMS) in SLE mice. Female adult Balb/c mice of 20-24 weeks of age were used as normal mice (n = 10), whereas female MRL/lpr mice of 12-24 weeks of age were divided into three groups (n = 10 in each group), including mild, moderate and severe SLE mice groups. The clinical characteristics of the SLE and Babl/c mice (i.e., body weight, joint thickness, lupus flare, proteinuria, leukocyturia and lymphadenopathy) were assessed. The plasma concentrations of anti-nuclear antibody (ANA) and anti-double stranded DNA antibody (anti-ds-DNA) were analyzed by an enzyme-linked immunosorbent assay, whereas the concentration of several key cytokines (IFN-γ, TNF-α, IL-6, IL-10, IL-2, IL-27, IL-12P70, IL-17A and IL-21) were analyzed by a Luminex multiplex assay. The gene expression profiles for differentiation of the T helper (Th) lymphocytes in splenic CD4(+) Th cells were assessed by RT-qPCR. Flow cytometry was used to measure the percentages of CD4(+)CD25(+)Foxp3(+) Treg cells and CD19(+)CD5(+)CD1d(+)IL-10(+) regulatory B (Breg) cells (IL-10(+) Bregs). Concentrations of anti-ds-DNA in the plasma samples collected from the LZ-SMS-treated (500 mg/kg/day oral administration for 7 days followed with 50 mg/kg/day intraperitoneal administration for 7 days), moderate and severe SLE mice decreased significantly compared with the PBS treated mice (P < 0.05). The gene expression levels of the induced regulatory T (iTreg) and natural Treg (nTreg) cells were significantly higher than those of the Th17, Th1 and "conventional Th cells vs. Treg cells" regulated genes following the LZ-SMS treatment (P < 0.05). The percentages of CD4(+)CD25(+)Foxp3(+) Treg cells collected from the splenic, thymic and peripheral blood cells, as well as the percentages of IL-10(+) Bregs collected from the splenic and thymic cells increased significantly in the LZ-SMS-treated SLE mice (P < 0.05) compared with the untreated PBS group. The ratio of the percentage of CD4(+)CD25(+)Foxp3(+) Treg cells to the percentage of CD4(+)CD25(-) effector T cells collected from the splenic, thymic and peripheral blood cells in LZ-SMS-treated moderate and severe SLE mice increased significantly compared with the untreated PBS group (P < 0.05). Furthermore, a comparison with the PBS treatment group revealed significant decreases in the concentrations of several inflammatory cytokines, including IL-21, IL-10 and IL-17A (P < 0.05), as well as significant increases in the concentrations of IL-2 and IL-12P70 in the LZ-SMS treated SLE mice (P < 0.05). LZ-SMS treatment led to significant increases in the percentages of CD4(+)CD25(+)Foxp3(+) Treg and IL-10(+) Breg cells, together with a reduction in the plasma concentrations of several inflammatory cytokines and the down-regulated expression of the corresponding cytokine related genes in SLE mice. The clinical characteristics of the LZ-SMS-treated SLE mice also improved significantly.

Autologous peripheral blood haematopoietic stem cell transplantation for systemic lupus erythematosus: the observation of long-term outcomes in a Chinese centre.

PubMed

Cao, Can; Wang, Menglei; Sun, Jing; Peng, Xuebiao; Liu, Qifa; Huang, Liang; Chai, Yanyan; Lai, Kuan; Chen, Pingjiao; Liu, Qingxiu; Li, Qian; Peng, Yusheng; Xiong, Hao; Zhang, Jing; Chen, Minghua; Zeng, Kang

2017-01-01

We aimed to evaluate the safety and long-term efficacy of autologous peripheral blood haematopoietic stem cell transplantation (APHSCT). We did not want to evaluate the efficacy of antibodies but rather the clinical response by investigating progression-free survival and serologic response by assessing autoantibody titres and complement levels. Overall, 22 patients with SLE (17 females; median age, 23 years) undergoing APHSCT were included. The 3-year progression-free survival (PFS) was 77.27% at our centre. We found that all the patients survived over three years. The 5-year PFS and overall survival (OS) rate was 67.90% and 95.20%. The titres of antinuclear antibody (ANA), anti-double-stranded deoxyribonucleic acid antibody (anti-dsDNA), anti-Sm antibody, and 24-h urinary protein significantly decreased, while complements 3 (C3) and C4 normalised at 100 days after transplantation (p<0.05). Kidney re-biopsy revealed a decrease in immune complex deposits in patients with remission. The incidence of CMV reactivation was 59.09% after transplantation in 3 years. Pregnancy and childbirth were reported in three female patients after transplantation. The risk of post-transplantation complications persisted for many years. Immunoablation followed by APHSCT has the potential to induce long-term clinical and serologic remissions despite withdrawal of immunosuppressive maintenance therapy. While relapses may occur, in our small cohort of patients we found no predictive markers for relapse development by analysing antibody and complement levels and urinary proteinuria.

Lupus erythematosus tumidus: a clinical and histological study of 25 cases.

PubMed

Rodriguez-Caruncho, C; Bielsa, I; Fernández-Figueras, M T; Roca, J; Carrascosa, J M; Ferrándiz, C

2015-06-01

Lupus erythematosus tumidus (LET) is a subtype of cutaneous lupus erythematosus (CLE) that has been well characterized in recent years. However, some controversy still remains concerning the histological features of epidermal involvement. The objective of this report is to describe the clinical and microscopic features of LET in patients diagnosed at Hospital Universitari Germans Trias i Pujol, Spain. We conducted a retrospective study of 25 patients with a diagnosis of LET. All patients presented with typical LET lesions (smooth, erythematous plaques without macroscopic epidermal changes, such as follicular plugs or scale, that resolved without residual scarring or hypopigmentation). None of the patients fulfilled the criteria for systemic lupus erythematosus during follow-up. Test results for antinuclear antibodies were positive in five patients (20%), with titres below one of 320 in all cases. Twenty-two patients (88%) required antimalarial therapy; response was good in 70% and moderate response in 30%. Minor epidermal alterations were observed in 52% of biopsy specimens, with focal basal vacuolization being the most frequent. LET is a variant of CLE that has distinctive clinical, histologic and prognostic features. Unlike the patients in the case series previously described in the literature, most of our patients required treatment with antimalarials. Histology revealed mild epidermal alterations in a significant percentage of patients. Thus, in our opinion, the absence of microscopic epidermal alterations is not constant in LET. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Idiopathic avascular necrosis of the femoral heads in five members of a Moroccan family.

PubMed

Sekkat, Jihane; Rachidi, Ouafaa; Janani, Saadia; Mkinsi, Ouafaa

2012-10-01

Avascular necrosis (AVN) is idiopathic in about 40% of cases. The pathophysiology of avascular necrosis remains incompletely elucidated. Here, we report a case that underlines the role for inherited factors in AVN of the femoral heads. Idiopathic AVN of the femoral heads occurred in five members of the same family (a woman, her two paternal aunts, her male paternal cousin and her female paternal cousin) at a mean age of 42.4 years (range, 33-58 years). Standard pelvic radiographs showed Arlet and Ficat stage 4 AVN in three patients and stage 3 in two patients. None of the patients had a history of glucocorticoid therapy, alcohol abuse, or trauma. All five patients underwent investigations for a cause, including blood cell counts, a lipid profile, coagulation tests, testing for antinuclear antibodies, hemoglobin electrophoresis, ultrasonography of the abdomen, and standard radiographs of the long limb bones. The results were normal or negative, ruling out known hereditary causes of AVN such as sickle cell anemia and Gaucher disease. Many cases of familial AVN of the femoral head have been described in patients with sickle cell anemia or Gaucher disease. However, only five families with idiopathic familial AVN of the femoral heads have been reported (three in the US and two in Taiwan). All the patients in these families had isolated bilateral AVN of the femoral heads without AVN at other sites. Copyright © 2012. Published by Elsevier SAS.

Use of total lymphoid irradiation (TLI) in studies of the T cell dependence of autoantibody production in rheumatoid arthritis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tanay, A.; Strober, S.; Logue, G.L.

1984-02-01

The effect of total lymphoid irradiation (TLI) on T cell-dependent and -independent humoral immune responses was studied in patients with intractable rheumatoid arthritis (RA). The serum levels of several autoantibodies and of antibodies to diphtheria (DT) and tetanus (TT) toxoids and to pneumococcal polysaccharide (PPS; 12 antigenic types) were studied before and after TLI. In addition, the patients were given a booster injection of DT and TT and a single injection of pneumococcal vaccine after radiotherapy. Antibody levels to DT and TT decreased about twofold after TLI and did not rise significantly after a booster injection. However, there was nomore » reduction in antibody levels to PPS after TLI, and a significant rise in titers was observed after a single vaccination. The serum levels of rheumatoid factor (RF), anti-nuclear antibody (ANA), and granulocyte associated IgG rose slightly after TLI. Thus, the autoantibodies and antibodies to polysaccharides appear to be relatively independent of helper T cell function, which is markedly reduced after TLI. On the other hand, antibodies to protein antigens such as DT and TT appear to be more closely dependent upon T helper function in man, as has been reported in rodents. The findings suggest that T cell-independent autoantibody responses alone do not maintain the joint disease activity in RA, because improvement in joint disease after TLI has been reported.« less

Epidemiological characteristics of patients with cutaneous lupus erythematosus.

PubMed

Avilés Izquierdo, J A; Cano Martínez, N; Lázaro Ochaita, P

2014-01-01

Lupus erythematosus is a chronic autoimmune inflammatory disease with a wide clinical spectrum and variable clinical course. Few studies have analyzed the characteristics of patients with only cutaneous lupus erythematosus (CLE). The aim of this study was to describe the epidemiological, clinical, and immunological characteristics of a series of patients diagnosed with CLE. An analysis was performed of the data from all patients over 18 years of age with a diagnosis of CLE and seen between January 1, 2007 and December 31, 2011 in a tertiary hospital. One hundred- one patients were included in the study. The mean age at diagnosis was 40 years and 84% were women. Subacute forms of presentation were observed in 94% of patients. The chronic discoid forms were localized to the head and neck in 79% of cases, whereas the subacute forms were on the trunk in 97% of cases. Patients with acute forms were positive for antinuclear, anti-DNA, anti-smooth muscle, and anti-RNP (ribonucleoprotein) antibodies, whereas anti-Ro and anti-La antibodies predominated in patients with subacute forms. Seventeen patients presented more than 1 subtype of CLE. Fifteen (88%) of these patients received immunosuppressor treatment versus 44 (52%) of the other 84 patients with only 1 subtype of CLE. Patients with distinct subtypes of CLE present different clinical and immunological characteristics. Oral immunosuppressants are often needed to control the disease in a large proportion of patients with different subtypes of CLE. Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.

Murine Lupus Susceptibility Locus Sle1a Requires the Expression of two Subloci to Induce Inflammatory T Cells

PubMed Central

Cuda, Carla M.; Zeumer, Leilani; Sobel, Eric S.; Croker, Byron P.; Morel, Laurence

2010-01-01

The NZM2410-derived Sle1a lupus susceptibility locus induces activated autoreactive CD4+ T cells and reduces the number and function of Foxp3+ regulatory T cells. In this study, we first showed that Sle1a contributes to autoimmunity by increasing anti-nuclear antibody production when expressed on either NZB or NZW heterozygous genomes, and by enhancing the chronic graft vs. host disease response indicating an expansion of the autoreactive B cell pool. Screening two non-overlapping recombinants, the Sle1a.1 and Sle1a.2 intervals that cover the entire Sle1a locus, revealed that both Sle1a.1 and Sle1a.2 were necessary for the full Sle1a phenotype. Sle1a.1, and to a lesser extent Sle1a.2, significantly affected CD4+ T cell activation as well as Treg differentiation and function. Sle1a.2 also increased the production of autoreactive B cells. Since the Sle1a.1 and Sle1a.2 intervals contain only one and 15 known genes, respectively, this study considerably reduces the number of candidate genes responsible for the production of autoreactive T cells. These results also demonstrate that the Sle1 locus is an excellent model for the genetic architecture of lupus, in which a major obligate phenotype results from the co-expression of multiple genetic variants with individual weak effects. PMID:20445563

Clinical significance of autoantibodies in autoimmune hepatitis.

PubMed

Liberal, Rodrigo; Mieli-Vergani, Giorgina; Vergani, Diego

2013-10-01

The accurate diagnosis and classification of autoimmune hepatitis (AIH) rely upon the detection of characteristic autoantibodies. Positivity for anti-nuclear (ANA) and/or anti-smooth muscle (SMA) autoantibodies defines AIH type 1 (AIH-1), whereas anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) define AIH type 2 (AIH-2). ANA and SMA, and less commonly anti-LKM1, have also been detected in de-novo autoimmune hepatitis developing after liver transplantation, a condition that may affect patients transplanted for non-autoimmune liver disease. The diagnostic autoantibodies associated with AIH-1 are also detected in the paediatric AIH/sclerosing cholangitis overlap syndrome, referred to as autoimmune sclerosing cholangitis (ASC). ASC, like adult primary sclerosing cholangitis, is often associated with atypical perinuclear anti-neutrophil cytoplasmic autoantibodies (p-ANCA), although p-ANCA are also detected in other autoimmune liver diseases. These associations highlight the necessity for simple and prompt diagnostic autoantibody testing, and the requirement for the accurate interpretation of the results of the tests in the clinical context. Fine-mapping of antigenic autoantibody targets has facilitated the development of rapid molecular assays that have the potential to revolutionise the field if properly standardised and when used in combination with classical immunofluorescence. Despite their diagnostic significance, the pathogenic role of the various autoantibodies and the mechanisms by which they can potentially inflict damage onto the liver cell remain a topic for further research. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of human cytochrome P450s as autoantigens.

PubMed

Manns, M P; Johnson, E F

1991-01-01

Antimicrosomal antibodies in inflammatory liver diseases all seem to be directed against members of the cytochrome P450 family of proteins. These autoantigens seem to be genetically polymorphic, the autoantibodies are inhibitory, and the autoepitopes are generally conserved among species. Anti-P450 autoantibodies share these characteristics with other autoantibodies, for example, antinuclear antibodies in systemic lupus erythematosus. The identification of P450s as human autoantigens is clinically important. Diagnostic tests will be developed on the basis of cloned antigen, facilitating a better diagnosis of drug-induced and idiopathic autoimmune hepatitis. It is unknown what triggers autoantibody production against cytochrome P450 proteins. Furthermore, their pathogenetic role and thus their involvement in tissue destruction is unclear. In this context LKM1 autoantibodies may serve as a model. Although LKM1 antibodies are inhibitory, all LKM1 antibody-positive patients tested so far are extensive metabolizers for drug metabolism mediated by P450IID6 and express this protein in their livers. Thus, the inhibitory LKM1 autoantibody does not sufficiently penetrate through the intact liver cell membrane to inhibit enzyme function in vivo. Presumably, tissue destruction in autoimmune hepatitis is mediated by liver-infiltrating T lymphocytes. T lymphocytes have been cloned from liver tissue that specifically proliferate in the presence of recombinant cytochrome P450IID6. The construction of overlapping cDNA subclones is also valuable to identify immunodominant B cell as well as relevant T cell epitopes.

[Autoimmune hepatitis in a girl with presence of anti-LKM1 antibodies].

PubMed

Larraín, F; Miquel, J F; González, S

1997-06-01

Autoimmune hepatitis is an inflammatory liver disease characterized by dense mononuclear cell infiltrate in the portal tract, and serologically by the presence of non-organ and liver-specific autoantibodies and increased levels of gammaglobulins in the absence of a known etiology. Three subgroups of autoimmune hepatitis have been recognized, depending on the nature of the autoantibody present in the serum: Type 1 autoimmune hepatitis, associated with smooth-muscle (SMA) or antinuclear antibody (ANA) seropositivity; type 2, with anti-liver/kidney microsome antibody (anti-LKM1), and type 3, with the absence of ANA, SMA and anti-LKM1 and presence of other autoantibodies such as anti-soluble liver antigen (SLA). Subtypes of chronic autoimmune hepatitis have clinically different features and prognoses. An 8 year old female patient presented mild jaundice of insidious onset. The liver was tender and enlarged. Serologic markers for A, B, C, E, Epstein Barr and cytomegalovirus were negative. The liver biopsy showed a histological picture consistent with chronic active hepatitis. High titers of anti-liver/kidney-microsome antibody were found by indirect immunofluorescence test, and this finding was confirmed by Western blot against specific liver microsome antigens. Therapy with prednisolone induced a clinical and biochemical remission after four weeks. The suspension of therapy under strict medical control produced a rapid relapse of clinical and biochemical features. The reinitiation of prednisolone was successful, and an alternate-day program was started and maintained until 8 months follow-up.

[Autoimmune hepatitis].

PubMed

Ostojić, Rajko

2003-01-01

Autoimmune hepatitis is an unresolving, hepatocellular inflammation of unknown cause that is characterized by the presence of periportal hepatitis on histologic examination, tissue autoantibodies in serum, and hypergammaglobulinemia. By international consensus, the designation autoimmune hepatitis has replaced alternative terms for the condition. Three types of autoimmune hepatitis have been proposed based on immunoserologic findings. Type 1 autoimmune hepatitis is characterized by the presence of antinuclear antibodies (ANA) or smooth muscle antibodies (SMA) (or both) in serum. Seventy percent of patients with type 1 of autoimmune hepatitis are women. This type is the most common form and accounts for at least 80% of cases. Type 2 is characterized by the presence of antibodies to liver-kidney microsome type 1 (anti-LKM1) in serum. Patients with this type of autoimmune hepatitis are predominantly children. Type 3 autoimmune hepatitis is characterized by the presence of antibodies to soluble liver antigen (anti-SLA) in serum. There are no individual features that are pathognomonic of autoimmune hepatitis, and its diagnosis requires the confident exclusion of other conditions. The large majority of patients show satisfactory response to corticosteroid (usually prednisone or prednisolone) therapy. For the past 30 years it has been customary to add azathioprine as a "steroid sparing" agent to allow lower doses of steroids to be used and remission, once achieved, can be sustained in many patients with azathioprine alone after steroid withdrawal. Patients with autoimmune hepatitis who have decompensated during or after corticosteroid therapy are candidates for liver transplantation.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy.

PubMed

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-07-01

Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy.Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test.Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology.The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment.

Antithyroid Antibodies Are Implicated in Epileptogenesis of Adult Patients With Epilepsy

PubMed Central

Tsai, Meng-Han; Fu, Ting-Ying; Chen, Nai-Ching; Shih, Fu-Yuan; Lu, Yan-Ting; Cheng, Mei-Yun; Chuang, Hung-Yi; Chuang, Yao-Chung

2015-01-01

Abstract Antithyroid antibodies (Abs) are associated with epilepsy in steroid-responsive encephalopathy, but have been rarely studied in unselected epilepsy patients. This study aimed to characterize the prevalence and associated factors of antithyroid Abs and other auto-Abs in adult patients with epilepsy. Epilepsy patients without autoimmune disorders were surveyed for antinuclear antibody (ANA), anti-β2 glycoprotein 1 antibody (aβ2GP1), anticardiolipin IgG Ab, antimicrosomal antibody (AMA), antithyroglobulin antibody (ATA), and thyroid function test. Of 319 patients, 75 (23.5%) were positive for at least 1 Ab. The most common Ab was anticardiolipin antibody (aCL) (30/319, 9.4%), followed by AMA (24/319, 7.5%), ANA (18/319, 5.6%), aβ2GP1 (18/319, 6.5%), and ATA (6/319, 3.25%). Antimicrosomal Abs were significantly more frequent in patients who were female, older at disease onset, older at the time of study, and had unknown seizure etiology. The presence of aCL was significantly associated with more frequent seizures. Most patients with antithyroid Ab were female and had focal seizures with unknown etiology. The association of different auto-Abs with different factors suggests that they may have different roles in adult patients with epilepsy. Recurrent seizures and certain antiepileptic medications may cause the production of aCL. The role of antithyroid Abs in adult focal epilepsy with unknown cause, especially in females, warrants further evaluation because of the potential implications on treatment. PMID:26131823

[What's new in internal medicine?].

PubMed

Blétry, O; Sene, T; Kahn, J-E; Ackermann, F; Charles, P; Leport, J; Piette, A-M

2009-12-01

Among diagnostic progress over the last three years in internal medicine, Antisynthetase Syndrome is now more easily recognised with the diffusion of laboratory tests for research of antibodies against tRNA synthetases (Anti JO1, anti PL7, Anti PL12). In two third of cases, these antibodies are found despite absence of antinuclear antibodies. Hence, we have to search them specifically in patients with polyarthritis associated with myositis, cutaneous manifestations (Raynaud phenomenom and "mechanic'hands") and interstitial lung disease. Discovery of asymptomatic mutation in the L ferritin coding sequence help us to better understand the "unexplained" hyperferritinemia. Initially described by japonese gastroenterologists, auto immune pancreatitis in fact a part of a systemic sclerosing disease with a biochemical hallmark: in crease of a subclass of immunoglobulins G (IgG4). A new pediatric disease due to a deficiency of the interleukin1 receptor antagonist (multifocal aseptic osteitis, periostitis, stomatitis, disseminated pustulosis) help us to better understand unexplained auto inflammatory diseases. The therapeutic progress is primarily due to an explosion of biological therapies, particularly four of them very useful for internists (in an off label use) : Interleukin 1 inhibitors (anakinra, Canakinumab) to treat some auto inflammatory diseases (cryopirin associated periodic syndromes and deficency of interleukin 1 receptor antagonist), monoclonal antibody against interleukin 5 (mepolizumab) to treat some hypereosinophilic syndromes and Churg and Strauss angiitis, interleukin 6 inhibitiors to treat multifocal Castleman's disease and adult Still disease, a monoclonal antibody against vascular endothelial growth factor (Bevacizumab) to treat hereditary hemorrhagic telangiectasia. Copyright 2009 Elsevier Masson SAS. All rights reserved.

Association of Discoid Lupus with Clinical Manifestations and Damage Accrual in PROFILE: A Multiethnic Lupus Cohort

PubMed Central

Santiago-Casas, Yesenia; Vilá, Luis M.; McGwin, Gerald; Cantor, Ryan S.; Petri, Michelle; Ramsey-Goldman, Rosalind; Reveille, John D.; Kimberly, Robert P.; Alarcón, Graciela S.; Brown, Elizabeth E.

2013-01-01

Objective To determine the clinical manifestations and disease damage associated with discoid rash in a large multiethnic systemic lupus erythematosus (SLE) cohort. Methods SLE patients (per ACR criteria), age ≥ 16 years, disease duration ≤ 10 years at enrollment, and defined ethnicity (African American, Hispanic or Caucasian), from a longitudinal cohort were studied. Socioeconomic-demographic features, clinical manifestations and disease damage [as per the Systemic Lupus International Collaborating Clinics Damage Index (SDI)] were determined. The association of DLE with clinical manifestations and disease damage was examined using multivariable logistic regression. Results A total of 2,228 SLE patients were studied. The mean (standard deviation, SD) age at diagnosis was 34.3 (12.8) years and the mean (SD) disease duration was 7.9 (6.0) years; 91.8% were women. Discoid lupus was observed in 393 (17.6%) of patients with SLE. In the multivariable analysis, patients with discoid lupus were more likely to be smokers and of African-American ethnicity, and to have malar rash, photosensitivity, oral ulcers, leukopenia and vasculitis. DLE patients were less likely to be of Hispanic (from Texas) ethnicity, and to have arthritis, end-stage renal disease (ESRD), and antinuclear, anti-dsDNA and anti-phospholipid antibodies. Patients with DLE had more damage accrual, particularly chronic seizures, scarring alopecia, scarring of the skin, and skin ulcers. Conclusion In this cohort of SLE patients, discoid lupus was associated with several clinical features including serious manifestations such as vasculitis and chronic seizures. PMID:22190480

Ciclosporin therapy for canine generalized discoid lupus erythematosus refractory to doxycycline and niacinamide.

PubMed

Banovic, Frane; Olivry, Thierry; Linder, Keith E

2014-10-01

Generalized discoid lupus erythematosus (DLE) is an autoimmune skin disease variant rarely reported in dogs. The antimalarial immunomodulator hydroxychloroquine has been suggested as maintenance therapy for generalized DLE in one dog, but several recurrences were noted in the 1 year follow-up of that patient. To describe the effective treatment of generalized DLE with ciclosporin in one dog. A 6-year-old, castrated male crossbred dog was presented with pruritic, well-demarcated annular to polycyclic, hyperpigmented plaques with marginal erythema on the dorsal head, neck, trunk and medial extremities; these had been nonresponsive to treatment with doxycycline and niacinamide. Investigation included complete blood count, serum chemistry profile, urinalysis, serum antinuclear antibody test, histopathological examination and direct immunofluorescence testing of skin biopsies. The presence of lymphocyte-rich interface dermatitis on histology, together with generalized chronic recurrent hyperpigmented plaques, was consistent with the diagnosis of a generalized variant of DLE. The absence of systemic signs and unremarkable laboratory tests excluded concurrent systemic lupus erythematosus. Treatment was initiated with oral dexamethasone and ciclosporin. After 1 month, dexamethasone was discontinued and oral ketoconazole was added to the therapeutic regimen. Four months later, pruritus and erythema resolved, with most skin lesions becoming impalpable. Over the last 6 months, the patient's DLE was maintained in remission with oral ciclosporin and ketoconazole in combination every 3 days. The combination of ciclosporin and ketoconazole appeared effective to induce and maintain lesion remission in this dog with generalized DLE. © 2014 ESVD and ACVD.

Mucocutaneous lupus erythematosus in dogs (21 cases).

PubMed

Olivry, Thierry; Rossi, Michael A; Banovic, Frane; Linder, Keith E

2015-08-01

The diagnosis of dogs with chronic juxtamucosal erosive lesions and histopathology typical of cutaneous lupus erythematosus (CLE) is unclear. We report herein 21 dogs with mucocutaneous erosive lesions and lupus-specific histopathology that we propose to be affected with mucocutaneous lupus erythematosus (MCLE), another variant of chronic CLE. Inclusion criteria were the presence of the following: (i) a >2 month history of chronic or recurrent skin lesions; (ii) erosions or ulcers predominating at mucosae or mucocutaneous junctions; (iii) microscopic lesions of CLE (i.e. a lymphocyte-rich interface dermatitis with basal keratinocyte damage); and (iv) a lack of complete remission following antimicrobials. Clinical questionnaires and skin biopsies were reviewed. Direct immunofluorescence and antinuclear antibody serology were performed whenever possible. More than half of the 21 dogs were German shepherds or their crosses. The disease affected mostly dogs in their mid-adulthood and there was an over-representation of females. Erosions and ulcers predominated at genital/perigenital and anal/perianal areas, with a lower frequency of involvement of periocular, perioral and perinasal regions. In these dogs, there were no clinical signs suggestive of an associated systemic lupus erythematosus. Microscopic lesions were specific for CLE, but they were patchy and often infected with bacteria. The most common immunological finding was focal IgG deposition at the basement membrane zone. Lesions responded to varying interventions, but oral glucocorticoids led to a shorter time to complete remission. Relapses were common upon treatment tapering. These observations support MCLE being another variant of canine CLE. © 2015 ESVD and ACVD.

Immunogenetic background of patients with autoimmune fatigue syndrome.

PubMed

Itoh, Y; Igarashi, T; Tatsuma, N; Imai, T; Yoshida, J; Tsuchiya, M; Murakami, M; Fukunaga, Y

2000-10-01

We have previously reported that approximately 50% of children with chronic nonspecific complaints were positive for antinuclear antibodies (ANA), and that a novel autoantibody to a 62 kD protein (anti-Sa) was found in 40% of these ANA-positive patients. Therefore, we proposed a distinct disease entity termed autoimmune fatigue syndrome (AIFS). We hypothesized that if autoimmune mechanisms did play an important role in the pathogenesis of AIFS, it is possible that it is immunogenetically regulated as observed in other autoimmune disorders. In order to examine the immunogenetic background of AIFS patients, HLA-A, -B, -C, and -DR loci were analyzed serologically in 61 AIFS patients. AIFS was found to be positively associated with the class I antigen HLA-B61 and with the class II antigen HLA-DR9, with odds ratios of 2.77 (p = 0.015, Pcorr = 0.48) and 2.60 (p= 0.012, Pcorr = 0.17), respectively. A negative association was also found between AIFS and HLA-DR2 with odds ratio of 0.25 (p = 0.029, Pcorr = 0.041). When comparing anti-Sa positive AIFS patients with healthy controls, the odds ratios associated with HLA-B61, DR9, and DR2 were 3.42 (p = 0.021, Pcorr = 0.22), 3.96 (p = 0.0011, Pcorr = 0.015), and 0.16 (p = 0.0022, Porr = 0.031), respectively. Thus, the HLA associations observed in this study suggested that immunogenetic background might play a role in AIFS.

[Eosinophilic pustular folliculitis and Ofuji disease. A case report].

PubMed

Rotoli, M; Carlesimo, F; Cavalieri, S

1995-10-01

We describe the case of a young man of Calabrian origin, who came to our observation for the appearance of erythematous pustular, intensely itching, lesions on the arms, trunk and, in a less extent, on the face. The blood count revealed a differential cell count of 16.8% eosinophils. Serum IgE levels were elevated (1000 IU/ml), and T cell subsets showed an increase in CD8+ and a decrease in CD4+ with an inversion of CD4+/CD8+ ratio (= 0.78). The result of the following investigations were either normal or negative: anti-(ds)DNA antibody, anti-nuclear antibody, anti-smooth muscle antibody, anti-striated muscle antibody, serological tests for viral, bacterial, fungal and parasitic diseases and cultural examination of the material from lesion. Histopathological examination of a biopsy specimen from the left arm showed the presence of abundant perivascular inflammatory infiltrate in the dermis and inflammatory infiltrate, with numerous eosinophils, around sebaceous glands. Taken together, all these data suggest the diagnosis of eosinophilic pustular folliculitis, a dermatosis of unknown etiology, with a histopathological picture identical to Ofuji's disease. Eosinophilic pustular folliculitis can be associated with HIV infection or haematological diseases (as non-Hodgkin lymphomas, myeloma, etc.); it was also reported in adult immunocompetent healthy individuals and in children. On the basis of our findings, we propose that this case should be classified as an idiopathic form, as we were not able to demonstrate any associated disease.

Chronic parotitis with multiple calcifications: Clinical and sialendoscopic findings.

PubMed

Jáuregui, Emmanuel; Kiringoda, Ruwan; Ryan, William R; Eisele, David W; Chang, Jolie L

2017-07-01

To characterize clinical, imaging, and sialendoscopy findings in patients with chronic parotitis and multiple parotid calcifications. Retrospective review. Clinical history, radiographic images and reports, lab tests, and operative reports were reviewed for adult patients with chronic parotitis and multiple parotid calcifications who underwent parotid sialendoscopy. Thirteen of 133 (10%) patients undergoing parotid sialendoscopy for chronic sialadenitis had more than one calcification in the region of the parotid gland. Seven patients (54%) were diagnosed with immune-mediated disease from autoimmune parotitis (positive Sjögren's antibodies or antinuclear antibodies) or human immunodeficiency virus (HIV) disease. The six patients (46%) who did not have an immune-mediated disorder had most calcifications located anterior or along the masseter muscle. Eight of 13 patients (61%) had at least one calculus found in the parotid duct on sialendoscopy. Four patients (38%) had multiple punctate calcifications within the parotid gland, all of whom had either autoimmune parotitis or HIV. None of the proximal or punctate parotid calcifications posterior to the masseter were visualized on sialendoscopy. Chronic parotitis in conjunction with multiple parotid calcifications is uncommon and was identified in 10% of our cohort. We contrast two classifications of parotid calcifications: 1) intraductal stones that cause recurrent duct obstruction and are often located within the main parotid duct along or anterior to the masseter and 2) punctate intraparenchymal parotid gland calcifications that are not visualized on sialendoscopy and may represent underlying inflammatory disease. 4 Laryngoscope, 127:1565-1570, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Tolerability and immunogenicity of an inactivated enterovirus 71 vaccine in Chinese healthy adults and children: an open label, phase 1 clinical trial.

PubMed

Meng, Fan-Yue; Li, Jing-Xin; Li, Xiu-Ling; Chu, Kai; Zhang, Yun-Tao; Ji, Hong; Li, Liang; Liang, Zheng-Lun; Zhu, Feng-Cai

2012-05-01

In this open labeled phase 1 clinical trial with enterovirus 71 (EV71) vaccine (ClinicalTrials.gov number: NCT01267903) performed in Donghai County, Jiangsu Province, China, in January 2011. A total of 100 healthy participants, stratified by age (40 adults aged 16-22 y and 60 children aged 6-15 y), were enrolled from volunteers and sequentially received EV71 vaccines of 160U (only for children), 320U, or 640U on day 0 and 28, in a manner of dose escalation. All the participants were followed for 28 d after each shot. During the study period, 37 participants reported at least one injection-site or systemic adverse reaction. No case of grade 3 adverse reaction or serious adverse event (SAE) was observed. Also no dose-related increase in reaction rate was noticed. Pain at injection-site and fever were the most frequently reported local and systematic reaction, respectively. The studied EV71 vaccines demonstrated acceptable tolerability and no anti-nuclear antibody (ANA) seropositive was detected pre or post vaccinations in participants. Also, no clinically significant abnormal change for the liver or kidney function indexes was found. In the according-to-protocol cohort for immunogenicity, it was observed one dose of EV71 vaccine elicited good immune response in the participants, especially for the ones with sero-positive baseline. No obvious dose-response relationship for immunogenicity was found.

Usefulness of antibodies and minor salivary gland biopsy in the study of sicca syndrome in daily clinical practice.

PubMed

Santiago, Maria Lida; Seisdedos, Maria Renata; Garcia Salinas, Rodrigo Nicolás; Catalán Pellet, Antonio; Villalón, Liliana; Secco, Anastasia

2015-01-01

To assess the association between histologic findings in the minor salivary gland biopsy (MSGB) and anti La (La/SS-B)y antiRo antibodies (Ro/SS-A), antinuclear antibodies (ANA) and Rheumatoid Factor (RF),and compare the value of the latter as diagnostic tests with MSGB, considered as the gold standard. Patients with suspected Primary Sjögren Syndrome (PSS) referred for MSGB were included. Antibody measurements were performed. Grade III and IV biopsy results were considered positive. Two hundred and eighteen (218) patients were included, 95% females, with a median age of 54 years and 12 months median duration of sicca symptoms. 36 of the biopsies were positive. 33% of patients had positive anti Ro/SS-A anti La/SS-B antibodies, 62% had positive ANA, and 31% positive RF. A statistically significant association was found between MSGB and anti Ro/SS-A anti La/SS-B, ANA and RF. ANA were the most sensitive antibodies (84%. 95% CI: 75- 92), and the most specific were: Anti Ro/ SS-A and/or anti La/ SS-B (78%. 95% CI: 71-85) and RF (78%. 95% CI: 69-87). On PSS clinical suspicion, anti Ro/ SS-A y anti La/ SS-B antibodies have a great value to achieve the diagnosis, with MSGB useful for diagnosis of seronegative patients. The results also suggest the importance of ANA and RF for PSS classification. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

Bilateral parotid enlargement due to malnutrition under the influence of the media in an adolescent in Lithuania.

PubMed

Mieliauskaite, Diana; Venalis, Algirdas; Graziene, Vida; Kirdaite, Gailute

2007-07-01

The elimination of censorship for the media in post-communist countries in transition has contributed to increases in the prevalence of several medical problems. Children and adolescents are particularly vulnerable to the messages conveyed through the media, which influence their perceptions and behaviour. We describe a case of bilateral parotid enlargement due to malnutrition under the influence of self-prescribed diet in an adolescent. A 15-year-old girl reported to our institution under suspicion of Sjögren's syndrome for medical advice. Two months ago she developed persistent bilateral parotid enlargement and a dry mouth. Her medical history revealed a weight loss due to "self-prescribed" reduce diet. Social questioning clarified high use of the media and influence on the body concept and self image. On extra oral examination, a diffuse parotid enlargement was seen bilaterally. The examination of the mouth showed a low moisture level of the intraoral mucosa. The unstimulated whole salivary flow rate was 2 ml in 15 min. Laboratory findings evidenced anemia (107 g/l). The serum albumin concentration indicated a reduced level (28 g/l). Search for antinuclear antibodies, anti-SSA antibodies, anti-SSB, -Sm, -RNP and anti-double-stranded DNA antibodies was negative. Evaluation for antibodies against hepatitis C, cytomegalovirus and Epstein-Barr virus infection and HIV rendered negative results. A histopathologic examination of labial salivary gland biopsy revealed a picture of sialoadenosis. From the above investigations, a diagnosis of sialoadenosis due to malnutrition was made.

Autoimmune hepatitis triggered by acute hepatitis A.

PubMed

Tanaka, Hiroto; Tujioka, Hiroto; Ueda, Hiroki; Hamagami, Hiroko; Kida, Youhei; Ichinose, Masakazu

2005-10-14

The patient was a 57-year-old woman presenting with jaundice as the chief complaint. She began vomiting on July 10, 2003. Jaundice was noted and admitted to our hospital for thorough testing. Tests on admission indicated severe hepatitis, based on: aspartate aminotransferase (AST), 1 076 IU/L; alanine aminotransferase (ALT), 1 400 IU/L; total bilirubin (TB), 20.9 mg/dL; and prothrombin time rate (PT%), 46.9%. Acute hepatitis A (HA) was diagnosed based on negative hepatitis B surface antigen and hepatitis C virus RNA and positive immunoglobulin (Ig) M HA antibody, but elevation of anti-nuclear antigen (X320) and IgG (3 112 mg/dL) led to suspicion of autoimmune hepatitis (AIH). Plasma exchange was performed for 3 d from July 17, and steroid pulse therapy was performed for 3 d starting on July 18, followed by oral steroid therapy. Liver biopsy was performed on August 5, and the results confirmed acute hepatitis and mild chronic inflammation. Levels of AST and ALT normalized, so dose of oral steroid was markedly reduced. Steroid therapy was terminated after 4 mo, as the patient had glaucoma. Starting 3 mo after cessation of steroid therapy, levels of AST and ALT began to increase again. Another liver biopsy was performed and AIH was diagnosed based on serum data and biopsy specimen. Oral steroid therapy was reinitiated. Levels of AST and ALT again normalized. The present case was thus considered to represent AIH triggered by acute HA.

Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis - a prospective cohort study.

PubMed

Weitoft, Tomas; Rönnelid, Johan; Knight, Ann; Lysholm, Jörgen; Saxne, Tore; Larsson, Anders

2014-06-20

Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA). In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor). During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002). Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse.

Legal and Regulatroy Obstacles to Nuclear Fission Technology in Space

NASA Astrophysics Data System (ADS)

Force, Melissa K.

2013-09-01

In forecasting the prospective use of small nuclear reactors for spacecraft and space-based power stations, the U.S. Air Force describes space as "the ultimate high ground," providing access to every part of the globe. But is it? A report titled "Energy Horizons: United States Air Force Energy Science &Technology Vision 2011-2026," focuses on core Air Force missions in space energy generation, operations and propulsion and recognizes that investments into small modular nuclear fission reactors can be leveraged for space-based systems. However, the report mentions, as an aside, that "potential catastrophic outcomes" are an element to be weighed and provides no insight into the monumental political and legal will required to overcome the mere stigma of nuclear energy, even when referring only to the most benign nuclear power generation systems - RTGs. On the heels of that report, a joint Department of Energy and NASA team published positive results from the demonstration of a uranium- powered fission reactor. The experiment was perhaps most notable for exemplifying just how effective the powerful anti-nuclear lobby has been in the United States: It was the first such demonstration of its kind in nearly fifty years. Space visionaries must anticipate a difficult war, consisting of multiple battles that must be waged in order to obtain a license to fly any but the feeblest of nuclear power sources in space. This paper aims to guide the reader through the obstacles to be overcome before nuclear fission technology can be put to use in space.

Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency

PubMed Central

Stepensky, Polina; Rensing-Ehl, Anne; Gather, Ruth; Revel-Vilk, Shoshana; Fischer, Ute; Nabhani, Schafiq; Beier, Fabian; Brümmendorf, Tim H.; Fuchs, Sebastian; Zenke, Simon; Firat, Elke; Pessach, Vered Molho; Borkhardt, Arndt; Rakhmanov, Mirzokhid; Keller, Bärbel; Warnatz, Klaus; Eibel, Hermann; Niedermann, Gabriele; Elpeleg, Orly

2015-01-01

Autoimmune cytopenia is a frequent manifestation of primary immunodeficiencies. Two siblings presented with Evans syndrome, viral infections, and progressive leukopenia. DNA available from one patient showed a homozygous frameshift mutation in tripeptidyl peptidase II (TPP2) abolishing protein expression. TPP2 is a serine exopeptidase involved in extralysosomal peptide degradation. Its deficiency in mice activates cell death programs and premature senescence. Similar to cells from naïve, uninfected TPP2-deficient mice, patient cells showed increased major histocompatibility complex I expression and most CD8+ T-cells had a senescent CCR7-CD127−CD28−CD57+ phenotype with poor proliferative responses and enhanced staurosporine-induced apoptosis. T-cells showed increased expression of the effector molecules perforin and interferon-γ with high expression of the transcription factor T-bet. Age-associated B-cells with a CD21− CD11c+ phenotype expressing T-bet were increased in humans and mice, combined with antinuclear antibodies. Moreover, markers of senescence were also present in human and murine TPP2-deficient fibroblasts. Telomere lengths were normal in patient fibroblasts and granulocytes, and low normal in lymphocytes, which were compatible with activation of stress-induced rather than replicative senescence programs. TPP2 deficiency is the first primary immunodeficiency linking premature immunosenescence to severe autoimmunity. Determination of senescent lymphocytes should be part of the diagnostic evaluation of children with refractory multilineage cytopenias. PMID:25414442

The phototoxicity of vemurafenib: An investigation of clinical monochromator phototesting and in vitro phototoxicity testing.

PubMed

Woods, J A; Ferguson, J S; Kalra, S; Degabriele, A; Gardner, J; Logan, P; Ferguson, J

2015-10-01

Vemurafenib is a targeted therapy approved for the treatment of patients with metastatic melanoma harbouring the BRAF V600E mutation. Photosensitivity has been reported in over 50% of patients and has been demonstrated to involve at least the broadband UVA spectrum in most patients. Erythrocyte protoporphyrin levels have also been reported as elevated in some patients. We report the results of monochromator phototesting in one patient recorded before and while taking vemurafenib. Analysis of porphyrin levels was also conducted. After one month of vemurafenib therapy the patient demonstrated markedly increased light sensitivity in the UVA spectrum between 335 ± 27 nm, 365 ± 27 nm and 400 ± 27 nm. However responses in the UVB (305 ± 5 nm) and blue light (430 ± 27 nm) regions were normal. There was no abnormal immediate erythemal response. Pre-vemurafenib baseline phototesting was normal, as was repeat testing two months later when the patient was taking high doses of systemic steroid. No abnormal porphyrins were detected and the antinuclear antibody test was normal. In parallel studies, HaCaT keratinocytes incubated with vemurafenib were killed by UVA but not by visible (blue) light and did not show evidence of detectable intracellular porphyrin in the presence of the drug. These data confirm vemurafenib induced UVA photosensitivity with a probable phototoxic mechanism not mediated via enhanced porphyrin. Copyright © 2015 Elsevier B.V. All rights reserved.

Developing Electronic Health Record Algorithms That Accurately Identify Patients With Systemic Lupus Erythematosus.

PubMed

Barnado, April; Casey, Carolyn; Carroll, Robert J; Wheless, Lee; Denny, Joshua C; Crofford, Leslie J

2017-05-01

To study systemic lupus erythematosus (SLE) in the electronic health record (EHR), we must accurately identify patients with SLE. Our objective was to develop and validate novel EHR algorithms that use International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification codes, laboratory testing, and medications to identify SLE patients. We used Vanderbilt's Synthetic Derivative, a de-identified version of the EHR, with 2.5 million subjects. We selected all individuals with at least 1 SLE ICD-9 code (710.0), yielding 5,959 individuals. To create a training set, 200 subjects were randomly selected for chart review. A subject was defined as a case if diagnosed with SLE by a rheumatologist, nephrologist, or dermatologist. Positive predictive values (PPVs) and sensitivity were calculated for combinations of code counts of the SLE ICD-9 code, a positive antinuclear antibody (ANA), ever use of medications, and a keyword of "lupus" in the problem list. The algorithms with the highest PPV were each internally validated using a random set of 100 individuals from the remaining 5,759 subjects. The algorithm with the highest PPV at 95% in the training set and 91% in the validation set was 3 or more counts of the SLE ICD-9 code, ANA positive (≥1:40), and ever use of both disease-modifying antirheumatic drugs and steroids, while excluding individuals with systemic sclerosis and dermatomyositis ICD-9 codes. We developed and validated the first EHR algorithm that incorporates laboratory values and medications with the SLE ICD-9 code to identify patients with SLE accurately. © 2016, American College of Rheumatology.

Clinicopathological review of immunohistochemically defined Kikuchi-Fujimoto disease-including some interesting cases.

PubMed

Seong, Gil Myeong; Kim, Jo-Heon; Lim, Gil Chai; Kim, Jinseok

2012-10-01

Kikuchi-Fujimoto Disease (KFD) is a benign, self-limited disease characterized by tender regional lymphadenopathy with fever. KFD remains a poorly defined disease, and no clear diagnostic criteria are available. Here, we assess the clinical, laboratory, and histopathologic findings of KFD cases and report two unusual cases. Forty KFD patients that underwent lymph node (LN) biopsy and diagnosed by immunohistochemical staining, from January 2003 to November 2010, were enrolled in this retrospective study. The patients had a mean age of 29.3 years, and 29 (72.5 %) were women. Affected LNs were mainly located unilaterally in the cervical area. Mean LN size was 15.3 mm. Twenty-eight (70 %) patients had LN tenderness, and 25 (62.5 %) patients had fever. Leukopenia was observed in 18 of 35 evaluable patients. C-reactive protein and erythrocyte sedimentation rate were elevated in most patients. Anti-nuclear antibody was positive in four of 19 evaluable patients, but all had been diagnosed with concurrent systemic lupus erythematosus. Histologically, the 40 cases were classified into three types, that is, as proliferative (37.5 %), necrotizing (55.0 %), or xanthomatous (7.5 %). Interesting cases: Case 1 was a 35-year-old female with KFD and uveitis, retinal vasculitis, and superior sagittal sinus thrombosis. Case 2 was a 47-year-old male with KFD and bone marrow involvement and presented with severe bicytopenia. Although KFD is an uncommon self-limited benign disorder, it must be included in the differential diagnosis of lymphadenopathy with fever and cytopenia. It is important that the clinical features of KFD be understood to reach a correct diagnosis.

Nuclear fluorescence serum reactivity on monkey oesophagus: a new antibody for the follow-up of coeliac disease?

PubMed Central

Picarelli, A; Sabbatella, L; Di Tola, M; Silano, M; Nicolussi, A; D'Inzeo, S; Coppa, A

2010-01-01

We have identified previously a nuclear fluorescence reactivity (NFR) pattern on monkey oesophagus sections exposed to coeliac disease (CD) patients' sera positive for anti-endomysium antibodies (EMA). The aim of the present work was to characterize the NFR, study the time–course of NFR-positive results in relation to gluten withdrawal and evaluate the potential role of NFR in the follow-up of CD. Twenty untreated, 87 treated CD patients and 15 healthy controls were recruited and followed for 12 months. Their sera were incubated on monkey oesophagus sections to evaluate the presence of NFR by indirect immunofluorescence analysis. Duodenal mucosa samples from treated CD patients were challenged with gliadin peptides, and thus the occurrence of NFR in culture supernatants was assessed. The NFR immunoglobulins (Igs) reactivity with the nuclear extract of a human intestinal cell line was investigated. Serum NFR was present in all untreated CD patients, persisted up to 151 ± 37 days from gluten withdrawal and reappeared in treated CD patients under dietary transgressions. Serum NFR was also detected in two healthy controls. In culture supernatants of coeliac intestinal mucosa challenged with gliadin peptides, NFR appeared before EMA. The Igs responsible for NFR were identified as belonging to the IgA2 subclass. The NFR resulted differently from EMA and anti-nuclear antibodies, but reacted with two nuclear antigens of 65 and 49 kDa. A new autoantibody, named NFR related to CD, was described. Furthermore, NFR detection might become a valuable tool in monitoring adherence to a gluten-free diet and identifying slight dietary transgressions. PMID:20529089

[A case of Poncet's disease (tuberculous rheumatism) in a patient with chronic renal failure undergoing hemodialysis therapy].

PubMed

Miki, Yusuke; Fujita, Yoshiro; Kawai, Ryosuke; Danbara, Atsushi; Ueno, Yukio; Ito, Yasuhiko

2003-10-01

A 78-year-old man who was undergoing hemodialysis therapy was admitted to our hospital because of sore throat, remittent cervical lymphadenopathy, and polyarthritis over the preceding 4 weeks. On admission, he had bilateral cervical lymphadenopathy. He complained of arthralgia associated with tenderness, warmth and swelling of both elbows, left side wrist and left shoulder joint. The C-reactive protein level on admission was 15.3 mg/dl. Rheumatoid factor, antinuclear antibodies, tuberculin skin test and blood culture were negative. Joint fluid was not aspirated. Radiographs of the joints did not reveal any abnormalities. Acid-fast bacilli were demonstrated in the smear of the cervical lymph node with a fluorochrome rhodamine-auramine stain. Mycobacterium tuberculosis DNA was identified by polymerase chain reaction. We found the presence of caseating granuloma on the biopsy specimens and M.tuberculosis was detected from culture. At that point, we diagnosed this patient as having tuberculous lymphadenitis. His general symptoms resolved rapidly after starting with a three-drug regimen consisting of isoniazid, rifampin and pyrazinamide. His polyarthritis also improved dramatically. Finally we considered that his polyarthritis was tuberculous rheumatism, also called Poncet's disease. Poncet's disease is characterized by sterile polyarthritis during active tuberculosis infection. It is considered a reactive arthritis, which is a different entity from tuberculous arthritis. Although this is a rare disease, we should be aware of it in hemodialysis patient clinics, because the incidence of tuberculosis infection has been reported to be increasing in patients with end-stage renal failure.

Female Infertility and Serum Auto-antibodies: a Systematic Review.

PubMed

Deroux, Alban; Dumestre-Perard, Chantal; Dunand-Faure, Camille; Bouillet, Laurence; Hoffmann, Pascale

2017-08-01

On average, 10 % of infertile couples have unexplained infertility. Auto-immune disease (systemic lupus erythematosus, anti-phospholipid syndrome) accounts for a part of these cases. In the last 20 years, aspecific auto-immunity, defined as positivity of auto-antibodies in blood sample without clinical or biological criteria for defined diseases, has been evoked in a subpopulation of infertile women. A systematic review was performed (PUBMED) using the MESH search terms "infertility" and "auto-immunity" or "reproductive technique" or "assisted reproduction" or "in vitro fertilization" and "auto-immunity." We retained clinical and physiopathological studies that were applicable to the clinician in assuming joint management of both infertility associated with serum auto-antibodies in women. Thyroid auto-immunity which affects thyroid function could be a cause of infertility; even in euthyroidia, the presence of anti-thyroperoxydase antibodies and/or thyroglobulin are related to infertility. The presence of anti-phospholipid (APL) and/or anti-nuclear (ANA) antibodies seems to be more frequent in the population of infertile women; serum auto-antibodies are associated with early ovarian failure, itself responsible for fertility disorders. However, there exist few publications on this topic. The methods of dosage, as well as the clinical criteria of unexplained infertility deserve to be standardized to allow a precise response to the question of the role of serum auto-antibodies in these women. The direct pathogenesis of this auto-immunity is unknown, but therapeutic immunomodulators, prescribed on a case-by-case basis, could favor pregnancy even in cases of unexplained primary or secondary infertility.

Autoimmune hepatitis.

PubMed

Vergani, D; Mieli-Vergani, G

1996-01-01

Autoimmune hepatitis is an inflammatory liver disease in which the immune system is believed to orchestrate an immune attack onto the liver cell. Current knowledge suggests that both T helper 1 (TH1) and TH2 programmes are involved in the generation of the liver damage. Release of TH2 cytokines leads to the production of autoantibodies to the hepatocyte membrane that recruit killer cells. TH1 cytokines induce macrophage activation which contributes to hepatocyte destruction. Patients commonly possess the "autoimmune" HLA A1/B8/DR3 haplotype and a silent gene at the C4A locus with consequent partial deficiency of the complement component C4. Two main types of autoimmune hepatitis are recognised according to the presence of circulating non-organ specific autoantibodies. Patients with smooth muscle antibody and/or antinuclear antibody may be adults or children, while patients with antiliver kidney microsomal type 1 (LKM1) antibody are usually children or very young adults. In both types there is a preponderance of females. LKM1 antibody is also present in a proportion of adult patients, mainly male, with chronic hepatitis C virus infection. This observation originally led to the suggestion that hepatitis C virus may be the cause of this form of autoimmune hepatitis, but several studies have shown that the epitopes target of the LKM1 antibody in autoimmune hepatitis and chronic hepatitis C virus infection differ. Although autoimmune hepatitis responds satisfactorily to immunosuppression in the short term, progression to cirrhosis is frequent. It is hoped that ongoing research will provide a better understanding of the pathogenic mechanisms of liver damage leading to a more effective and specific mode of treatment.

The Importance of Minor Salivary Gland Biopsy in Sjögren Syndrome Diagnosis and the Clinicopathological Correlation.

PubMed

Serin, Gürdeniz; Karabulut, Gonca; Kabasakal, Yasemin; Kandiloğlu, Gülşen; Akalin, Taner

2016-01-01

Minor salivary gland biopsy is one of the objective tests used in the diagnosis of Sjögren syndrome. The aim of our study was to compare the clinical and laboratory data of primary and secondary Sjögren syndrome cases with a lymphocyte score 3 and 4 in the minor salivary gland biopsy. Data from a total of 2346 consecutive minor salivary gland biopsies were retrospectively evaluated in this study. Clinical and autoantibody characteristics of 367 cases with lymphocyte score 3 or 4 and diagnosed with primary or secondary Sjögren syndrome were compared. There was no difference between lymphocyte score 3 and 4 primary Sjögren syndrome patients in terms of dry mouth, dry eye symptoms and Schirmer test results but Anti-Ro and Antinuclear Antibody positivity was statistically significantly higher in cases with lymphocyte score 4 (p= 0.025, p= 0.001). Anti-Ro test results were also found to be statistically significantly higher in secondary Sjögren syndrome patients with lymphocyte score 4 (p= 0.048). In this study, the high proportion of cases with negative autoantibody but positive lymphocyte score is significant in terms of showing the contribution of minor salivary gland biopsy to Sjögren syndrome diagnosis. Lymphocyte score 3 and 4 cases were found to have similar clinical findings but a difference regarding antibody positivity in primary Sjögren syndrome. We believe that cases with lymphocyte score 4 may be Sjögren syndrome cases whose clinical manifestations are relatively established and higher autoantibody levels are therefore found.

Evolving concepts of diagnosis, pathogenesis, and therapy of Sjögren's syndrome.

PubMed

Fox, R I; Törnwall, J; Maruyama, T; Stern, M

1998-09-01

Differences in diagnostic criteria for Sjögren's Syndrome (SS) have led to confusion in the research literature and in clinical practice. A particular challenge is the clinical diagnosis of the patients with sicca symptoms, fibromyalgia, chronic fatigue, vague cognitive defects, and a low titer antinuclear antibody. Until recently, many of these patients would have been classified as primary SS using the European criteria. A suggested revision of the European criteria will require inclusion of anti SS-A antibody or characteristic minor salivary gland biopsy, leading to greater agreement between European and San Diego criteria. Recent studies have emphasized that lacrimal and salivary gland flow involves an entire "functional" unit that includes the mucosal surface (the site of inflammation), efferent nerve signals sent to the midbrain (lacrimatory and salvatory nucleus), efferent neural signals from the brain, and acinal/ductal structures in the gland. Thus, symptoms of dryness or pain can result from interferences with any part of this functional unit. The initiating antigens in SS remain unknown, but immune reactivity against SS-A, SS-B, fodrin, alpha- amylase, and carbonic anhydrase have been demonstrated in patients with established disease. The inflammatory process in the gland releases metalloproteinases that alter the relationship of epithelial cells to their matrix, an interaction that is necessary for glandular function and survival. Therapies for SS remain inadequate. In SS patients with immune-mediated extraglandular manifestation (ie, lung, kidney, skin, nerve), the therapeutic approach is similar to systemic lupus erythematosus, although these therapies have relatively little effect on tear or saliva flow.

Novel method for quantitative ANA measurement using near-infrared imaging.

PubMed

Peterson, Lisa K; Wells, Daniel; Shaw, Laura; Velez, Maria-Gabriela; Harbeck, Ronald; Dragone, Leonard L

2009-09-30

Antinuclear antibodies (ANA) have been detected in patients with systemic rheumatic diseases and are used in the screening and/or diagnosis of autoimmunity in patients as well as mouse models of systemic autoimmunity. Indirect immunofluorescence (IIF) on HEp-2 cells is the gold standard for ANA screening. However, its usefulness is limited in diagnosis, prognosis and monitoring of disease activity due to the lack of standardization in performing the technique, subjectivity in interpreting the results and the fact that it is only semi-quantitative. Various immunological techniques have been developed in an attempt to improve upon the method to quantify ANA, including enzyme-linked immunosorbent assays (ELISAs), line immunoassays (LIAs), multiplexed bead immunoassays and IIF on substrates other than HEp-2 cells. Yet IIF on HEp-2 cells remains the most common screening method for ANA. In this study, we describe a simple quantitative method to detect ANA which combines IIF on HEp-2 coated slides with analysis using a near-infrared imaging (NII) system. Using NII to determine ANA titer, 86.5% (32 of 37) of the titers for human patient samples were within 2 dilutions of those determined by IIF, which is the acceptable range for proficiency testing. Combining an initial screening for nuclear staining using microscopy with titration by NII resulted in 97.3% (36 of 37) of the titers detected to be within two dilutions of those determined by IIF. The NII method for quantitative ANA measurements using serum from both patients and mice with autoimmunity provides a fast, relatively simple, objective, sensitive and reproducible assay, which could easily be standardized for comparison between laboratories.

Clinical and microscopic features of generalized discoid lupus erythematosus in dogs (10 cases).

PubMed

Banovic, Frane; Linder, Keith E; Uri, Maarja; Rossi, Michael A; Olivry, Thierry

2016-12-01

Generalized discoid lupus erythematosus (GDLE) is a newly recognized canine variant of chronic cutaneous lupus erythematosus (CLE) that is not well characterized. We report herein the signalment, clinical signs, treatment outcome, histopathology and immunological findings of 10 dogs with GDLE. Inclusion criteria were: (i) a >3 month history of generalized skin lesions indicating a chronic or recurrent nature; (ii) skin lesions resembling those of human GDLE; (iii) histopathology of CLE (lymphocyte-rich interface dermatitis). Direct immunofluorescence (IF) and antinuclear antibody serology were investigated whenever possible. Various breeds were affected in their mid- to late adulthood. Selection criteria of generalized multifocal, annular ("discoid") to polycyclic plaques with pigment changes, erythematous margin, adherent scaling, follicular plugging and central alopecia were shown in all dogs. In nine dogs, plaques contained mild to moderate central scarring with depigmentation and/or hyperpigmentation. There were no dogs in which the disease progressed to systemic lupus erythematosus within a median follow-up of 2.5 years. Per inclusion criteria, interface dermatitis occurred with basement membrane zone (BMZ) thickening, suprabasal apoptosis and/or dermal fibrosis in some dogs. Infundibular interface folliculitis was common; it sometimes transitioned to mural folliculitis in lower follicle segments, and occurred with follicular and sebaceous gland atrophy. The direct IF revealed patchy deposition of immunoglobulin IgG and IgM at the BMZ. Lesions responded to a variety of treatments, including ciclosporin, hydroxychloroquine, topical tacrolimus and tetracycline/niacinamide. Relapses were common after medications were tapered. These observations support the existence of a canine homologue of human GDLE. © 2016 ESVD and ACVD.

Clinical features and histological patterns of lupus nephritis in a single center of South India.

PubMed

Devadass, Clement Wilfred; Mysorekar, Vijaya Viswanath; Eshwarappa, Mahesh; Mekala, Lakshminarayanan; Siddaiah, M Gireesh; Channabasappa, K Gurudev

2016-01-01

Renal involvement occurs in up to 60% of patients with systemic lupus erythematosus (SLE) and signifies a poor prognosis. The class of lupus nephritis (LN), determined on renal biopsy evaluation, guides the therapeutic management and has prognostic connotations. Our aim is to determine the clinicolaboratory features and histopathological patterns of LN at presentation in our local (South Indian) population. The study was conducted in a tertiary care hospital in South India between 2009 and 2014 on SLE patients with clinical evidence of LN. The renal biopsies were examined by light and immunofluorescence microscopy and were classified according to the International Society of Nephrology/Renal Pathology Society Classification of LN. A total of 46 patients were included, with age range of 12-60 years and a female to male ratio of 8.2:1. Arthritis, dermatological manifestations, and fever occurred, respectively, in 43.5%, 39.1%, and 30.4% of the cases. Class IV LN was present in 17 (37.1%), Class III LN in ten (21.7%), Class II LN in nine (19.5%), Class V LN in eight (17.4%), Class I LN in one (2.2%), and Class VI LN in one (2.2%) patients. Antinuclear antibody (ANA) and dsDNA positivity were present, respectively, in 82.6% and 65.2% of the patients. The most common pattern of LN was Class IV LN followed by Class III LN. Relatively higher proportions of ANA and anti-dsDNA positivity were present in proliferative LN, and there was a high frequency of arthritis at presentation in our LN patients.

Abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome.

PubMed

Montaño-Loza, Aldo J; Crispín-Acuña, José Carlos; Remes-Troche, José María; Uribe, Misael

2007-01-01

Patients with primary Sjögren's syndrome may present liver involvement. Our goals were to establish the prevalence of abnormal hepatic biochemistries and clinical liver disease in patients with primary Sjögren's syndrome and correlate their presence with other clinical and laboratory features. Ninety-five patients with diagnosis of primary Sjögren's syndrome were studied. Data on gender, age, clinical features, liver biochemistries, tests of inflammation and autoimmunity, and concomitant diseases were collected. Forty-two patients (44%) had abnormal hepatic biochemistries, and of these 19 patients (20%) had clinical liver disease. Patients with abnormal hepatic biochemistries had higher frequency of autoimmune hypotiroidism, arthritis, vasculitis, Raynaud's phenomenon, higher sedimentation rate,and higher frequency of antinuclear and antimitochondrial antibodies than patients with normal liver biochemistries (P < 0.05 for each). Patients with clinical liver disease had higher frequency of arthritis, vasculitis, and higher frequency of antimitochondrial antibodies than patients without clinical liver disease (P < 0.05 for each). Twenty-one patients had diagnosis of a specific liver disease, such as hepatitis C virus infection (n = 11), autoimmune hepatitis (n = 2), primary biliary cirrhosis (n =5),nonalcoholic fatty liver disease (n = 2), and hepatitis B virus infection (n = 1). In half of patients with liver involvement a definitive cause could not be identified. Liver involvement is frequently found in patients with primary Sjögren's syndrome, and its presence is associated with clinical features of systemic disease, and markers of autoimmunity and inflammation. There may be a subgroup of patients with liver involvement secondary to primary Sjögren's syndrome.

Hematoxylin Bodies in Pediatric Bone Marrow Aspirates and Their Utility in the Diagnosis of Systemic Lupus Erythematosus.

PubMed

Xu, Min; Chisholm, Karen M; Fan, Guang; Stevens, Anne M; Rutledge, Joe C

2017-01-01

In our recent case report, the finding of lupus erythematosus (LE) cells in a bone marrow aspirate led to the diagnosis of systemic lupus erythematosus (SLE) and appropriate treatment, although the patient was not clinically suspected to have SLE. To determine whether LE cells are present in the bone marrow aspirates of SLE patients, but overlooked in routine bone marrow morphology review, bone marrow aspirates from 30 pediatric patients (15 with SLE and 15 with other diagnoses) evaluated by rheumatologists were reviewed. LE cells were found in the bone marrow aspirates of only 1 SLE patient and none in non-SLE patients. However, hematoxylin bodies were identified in 53% (8/15) of SLE patients. Neither hematoxylin bodies nor LE cells were found in the aspirates from patients with other disorders. Three additional pediatric patients identified prospectively were found to have hematoxylin bodies in the bone marrow aspirates. Although the diagnosis was not initially suspected, 2 of the 3 patients were subsequently diagnosed with SLE. All patients with hematoxylin bodies and SLE had antinuclear antibody titers ≥1:640 with a homogeneous staining pattern. In addition, bone marrow aspirates of 9 adult patients were reviewed, and neither LE cells nor hematoxylin bodies were identified. In summary, hematoxylin bodies were present in the bone marrow aspirates of many pediatric SLE patients, while LE cells were rare. The finding of hematoxylin bodies in pediatric bone marrow aspirates is a helpful and specific diagnostic clue that may lead to the diagnosis of SLE when other clinical features are nonspecific.

Japan's anti-nuclear weapons policy misses its target, even in the war on terrorism.

PubMed

DiFilippo, Anthony

2003-01-01

While actively working to promote the abolition of all nuclear weapons from the world since the end of the cold war, Japan's disarmament policies are not without problems. Promoting the elimination of nuclear weapons as Japan remains under the US nuclear umbrella creates a major credibility problem for Tokyo, since this decision maintains a Japanese deterrence policy at the same time that officials push for disarmament. Tokyo also advocates a gradual approach to the abolition of nuclear weapons, a decision that has had no effect on those countries that have been conducting sub-critical nuclear testing, nor stopped India and Pakistan from carrying out nuclear tests. Consistent with Article 9 of the Constitution, the Japanese war-renouncing constitutional clause, Tokyo toughened Japan's sizeable Official Development Assistance (ODA) programme in the early 1990s. Because of the anti-military guidelines included in Japan's ODA programme, Tokyo stopped new grant and loan aid to India and Pakistan in 1998 after these countries conducted nuclear tests. However, because of the criticism Japan faced from its failure to participate in the 1991 Gulf War, Tokyo has been seeking a new Japanese role in international security during the post-cold war period. Deepening its commitment to the security alliance with the US, Tokyo has become increasingly influenced by Washington's global polices, including the American war on terrorism. After Washington decided that Pakistan would be a key player in the US war on terrorism, Tokyo restored grant and loan aid to both Islamabad and New Delhi, despite the unequivocal restrictions of Japan's ODA programme.

[Dermatomyositis associated with anti-MDA5 antibodies and pneumocystis pneumonia: Two lethal cases].

PubMed

Aymonier, M; Abed, S; Boyé, T; Barazzutti, H; Fournier, B; Morand, J-J

2017-04-01

Dermatomyositis associated with anti-MDA-5 autoantibodies is a recently-described clinical entity. Herein we report two lethal cases involving pneumocystis pneumonia. Case n o  1. A 56-year-old male patient developed cutaneous symptoms consistent with dermatomyositis without muscular involvement. Antinuclear antibodies were present and anti-MDA5 auto-antibodies were identified. The scan showed interstitial lung disease without infection. Significant improvement was obtained with corticosteroids. One month later, the patient presented acute respiratory illness (hypoxemia: PaO 2 60mmHg, exacerbation of lung disease evidenced by a scan, and diagnosis of pneumocystis pneumonia on bronchoalveolar lavage). He died despite appropriate antibiotic therapy and immunosuppressant therapy. Case n o  2. The second case concerned a 52-year-old Vietnamese man who developed more atypical cutaneous symptoms of dermatomyositis without muscular involvement. ANAb responses were positive (1/400) and MDA5 was present. The patient was treated with corticosteroids (40mg/d), hydroxychloroquine, and intravenous immunoglobulin. After significant improvement, the patient developed an acute respiratory illness due to superinfection with pneumocystis and he died despite specific treatment and cyclophosphamide bolus. In dermatomyositis, anti-MDA5 antibody screening is essential for the prognosis since the disease carries a risk of complication with severe lung disease. Bronchial fibroscopy with bronchoalveolar lavage should be considered at the time of diagnosis. Our two cases suggest the need for early screening for pneumocystis pneumonia in the event of respiratory distress and possibly for prophylactic treatment at the start of immunosuppressant therapy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Prediction of Methotrexate Clinical Response in Portuguese Rheumatoid Arthritis Patients: Implication of MTHFR rs1801133 and ATIC rs4673993 Polymorphisms

PubMed Central

Lima, Aurea; Monteiro, Joaquim; Bernardes, Miguel; Sousa, Hugo; Azevedo, Rita; Seabra, Vitor; Medeiros, Rui

2014-01-01

Objective. Methotrexate (MTX), the most used drug in rheumatoid arthritis (RA) treatment, showing variability in clinical response, is often associated with genetic polymorphisms. This study aimed to elucidate the role of methylenetetrahydrofolate reductase (MTHFR) C677T and aminoimidazole carboxamide adenosine ribonucleotide transformylase (ATIC) T675C polymorphisms and clinicopathological variables in clinical response to MTX in Portuguese RA patients. Methods. Study included 233 RA patients treated with MTX for at least six months. MTHFR C677T and ATIC T675C polymorphisms were genotyped and clinicopathological variables were collected. Statistical analyses were performed and binary logistic regression method adjusted to possible confounding variables. Results. Multivariate analyses demonstrated that MTHFR 677TT (OR = 4.63; P = 0.013) and ATIC 675T carriers (OR = 5.16; P = 0.013) were associated with over 4-fold increased risk for nonresponse. For clinicopathological variables, noncurrent smokers (OR = 7.98; P = 0.001), patients positive to anti-cyclic citrullinated peptide (OR = 3.53; P = 0.004) and antinuclear antibodies (OR = 2.28; P = 0.045), with higher health assessment questionnaire score (OR = 2.42; P = 0.007), and nonsteroidal anti-inflammatory drug users (OR = 2.77; P = 0.018) were also associated with nonresponse. Contrarily, subcutaneous administration route (OR = 0.11; P < 0.001) was associated with response. Conclusion. Our study suggests that MTHFR C677T and ATIC T675C genotyping combined with clinicopathological data may help to identify patients whom will not benefit from MTX treatment and, therefore, assist clinicians in personalizing RA treatment. PMID:24967362

Protein adducts of malondialdehyde and 4-hydroxynonenal contribute to trichloroethene-mediated autoimmunity via activating Th17 cells: Dose- and time-response studies in female MRL+/+ mice

PubMed Central

Wang, Gangduo; Wang, Jianling; Fan, Xiuzhen; Ansari, G. A. S.; Khan, M. Firoze

2011-01-01

Trichloroethene (TCE), a common occupational and environmental toxicant, is known to induce autoimmunity. Previous studies in our laboratory showed increased oxidative stress in TCE-mediated autoimmunity. To further establish the role of oxidative stress and to investigate the mechanisms of TCE-mediated autoimmunity, dose- and time- response studies were conducted in MRL+/+ mice by treating them with TCE via drinking water at doses of 0.5, 1.0 or 2.0 mg/ml for 12, 24 or 36 weeks. TCE exposure led to dose-related increases in malondialdehyde (MDA)-/hydroxynonenal (HNE)-protein adducts and their corresponding antibodies in the sera and decreases in GSH and GSH/GSSG ratio in the kidneys at 24 and 36 weeks, with greater changes at 36 weeks. The increases in these protein adducts and decreases in GSH/GSSG ratio were associated with significant elevation in serum anti-nuclear- and anti-ssDNA-antibodies, suggesting an association between TCE-induced oxidative stress and autoimmune response. Interestingly, splenocytes from mice treated with TCE for 24 weeks secreted significantly higher levels of IL-17 and IL-21 than did splenocytes from controls after stimulation with MDA-mouse serum albumin (MSA) or HNE-MSA adducts. The increased release of these cytokines showed a dose-related response and was more pronounced in mice treated with TCE for 36 weeks. These studies provide evidence that MDA- and or HNE-protein adducts contribute to TCE-mediated autoimmunity, which may be via activation of Th17 cells. PMID:22178267

Outcome predictors of intra-articular glucocorticoid treatment for knee synovitis in patients with rheumatoid arthritis – a prospective cohort study

PubMed Central

2014-01-01

Introduction Intra-articular glucocorticoid treatment (IAGC) is widely used for symptom relief in arthritis. However, knowledge of factors predicting treatment outcome is limited. The aim of the present study was to identify response predictors of IAGC for knee synovitis in patients with rheumatoid arthritis (RA). Methods In this study 121 RA patients with synovitis of the knee were treated with intra-articular injections of 20 mg triamcinolone hexacetonide. They were followed for six months and the rate of clinical relapse was studied. Non-responders (relapse within 6 months) and responders were compared regarding patient characteristics and knee joint damage as determined by the Larsen-Dale index. In addition, matched samples of serum and synovial fluid were analysed for factors reflecting the inflammatory process (C-reactive protein, interleukin 6, tumour necrosis factor alpha, vascular endothelial growth factor), joint tissue turnover (cartilage oligomeric matrix protein, metalloproteinase 3), and autoimmunity (antinuclear antibodies, antibodies against citrullinated peptides, rheumatoid factor). Results During the observation period, 48 knees relapsed (40%). Non-responders had more radiographic joint damage than responders (P = 0.002) and the pre-treatment vascular endothelial growth factor (VEGF) level in synovial fluid was significantly higher in non-responders (P = 0.002). Conclusions Joint destruction is associated with poor outcome of IAGC for knee synovitis in RA. In addition, higher levels of VEGF in synovial fluid are found in non-responders, suggesting that locally produced VEGF is a biomarker for recurrence of synovial hyperplasia and the risk for arthritis relapse. PMID:24950951

New side effect of TNF-alpha inhibitors: morphea.

PubMed

Stewart, Faith A; Gavino, Alde Carlo P; Elewski, Boni E

2013-01-01

An otherwise healthy 45-year-old man with a 3-year history of poorly controlled psoriasis (no arthritis) was treated with etanercept 50-mg subcutaneous injections twice weekly for 3 months and then once weekly. Alternative treatment options were either unavailable (long commute for phototherapy) or contraindicated (history of alcohol abuse). The patient initially tolerated etanercept well with significant clinical improvement and had an uneventful course; however, approximately 18 months after initiating therapy, he abruptly developed dusky, indurated, and tender plaques on his abdomen and thighs at the sites of etanercept injections (Figure 1). There was also diffuse woody induration involving his flanks and back where injections had not been performed. His only recent prior exposure to an injectable medication was rabies vaccination in his arm 1 year earlier. The patient denied any systemic symptoms. Upon noting these findings, etanercept was immediately discontinued. Biopsy of an indurated plaque on his right lower abdomen revealed a superficial and deep perivascular lymphoplasmacytic inflammatory infiltrate in a background of thickened and hyalinized collagen fibers with notable loss of perieccrine fat (Figure 2). These features were most consistent with the inflammatory stage of morphea. Further work-up revealed a negative antinuclear antibody, anti-double-stranded DNA, anti-Scl-70, and anti-centromere. Borrelia titers were not obtained. The differential diagnosis included scleredema and scleromyxedema; serum and urine protein electrophoresis were within normal limits. The sites were treated with intralesional corticosteroids. During the next 3 months, there was minimal progression of disease although the plaques of morphea had not yet resolved.

IRF4 Deficiency Abrogates Lupus Nephritis Despite Enhancing Systemic Cytokine Production

PubMed Central

Lech, Maciej; Weidenbusch, Marc; Kulkarni, Onkar P.; Ryu, Mi; Darisipudi, Murthy Narayana; Susanti, Heni Eka; Mittruecker, Hans-Willi; Mak, Tak W.

2011-01-01

The IFN-regulatory factors IRF1, IRF3, IRF5, and IRF7 modulate processes involved in the pathogenesis of systemic lupus and lupus nephritis, but the contribution of IRF4, which has multiple roles in innate and adaptive immunity, is unknown. To determine a putative pathogenic role of IRF4 in lupus, we crossed Irf4-deficient mice with autoimmune C57BL/6-(Fas)lpr mice. IRF4 deficiency associated with increased activation of antigen-presenting cells in C57BL/6-(Fas)lpr mice, resulting in a massive increase in plasma levels of TNF and IL-12p40, suggesting that IRF4 suppresses cytokine release in these mice. Nevertheless, IRF4 deficiency completely protected these mice from glomerulonephritis and lung disease. The mice were hypogammaglobulinemic and lacked antinuclear and anti-dsDNA autoantibodies, revealing the requirement of IRF4 for the maturation of plasma cells. As a consequence, Irf4-deficient C57BL/6-(Fas)lpr mice neither developed immune complex disease nor glomerular activation of complement. In addition, lack of IRF4 impaired the maturation of Th17 effector T cells and reduced plasma levels of IL-17 and IL-21, which are cytokines known to contribute to autoimmune tissue injury. In summary, IRF4 deficiency enhances systemic inflammation and the activation of antigen-presenting cells but also prevents the maturation of plasma cells and effector T cells. Because these adaptive immune effectors are essential for the evolution of lupus nephritis, we conclude that IRF4 promotes the development of lupus nephritis despite suppressing antigen-presenting cells. PMID:21742731

Biomechanics, diagnosis, and treatment outcome in inflammatory myopathy presenting as oropharyngeal dysphagia

PubMed Central

Williams, R B; Grehan, M J; Hersch, M; Andre, J; Cook, I J

2003-01-01

Aims: In patients with inflammatory myopathy and dysphagia, our aims were to determine: (1) the diagnostic utility of clinical and laboratory indicators; (2) the biomechanical properties of the pharyngo-oesophageal segment; (3) the usefulness of pharyngeal videomanometry in distinguishing neuropathic from myopathic dysphagia; and (4) clinical outcome. Methods: Clinical, laboratory, and videomanometric assessment was performed in 13 patients with myositis and dysphagia, in 17 disease controls with dysphagia (due to proven CNS disease), and in 22 healthy age matched controls. The diagnostic accuracy of creatine kinase (CPK), erythrocyte sedimentation rate, antinuclear antibody, and electromyography (EMG) were compared with the gold standard muscle biopsy. The biomechanical properties of the pharyngo-oesophageal segment were assessed by videomanometry. Results: Mean time from dysphagia onset to the diagnosis of myositis was 55 months (range 1–180). One third had no extrapharyngeal muscle weakness; 25% had normal CPK, and EMG was unhelpful in 28%. Compared with neurogenic controls, myositis patients had more prevalent cricopharyngeal restrictive disorders (69% v 14%; p=0.0003), reduced upper oesophageal sphincter (UOS) opening (p=0.01), and elevated hypopharyngeal intrabolus pressures (p=0.001). Videomanometric features favouring a myopathic over a neuropathic aetiology were: preserved pharyngeal swallow response, complete UOS relaxation, and normal swallow coordination. The 12 month mortality was 31%. Conclusions: The notable lack of supportive clinical signs and significant false negative rates for laboratory tests contribute to the marked delay in diagnosis. The myopathic process is strongly associated with restricted sphincter opening suggesting that cricopharyngeal disruption is a useful adjunct to immunosuppressive therapy. The condition has a poor prognosis. PMID:12631653

Lamotrigine-induced tubulointerstitial nephritis and uveitis-atypical Cogan syndrome.

PubMed

Kolomeyer, Anton M; Kodati, Shyam

2015-12-01

To report a case of lamotrigine-induced tubulointerstitial nephritis and uveitis (TINU)-atypical Cogan syndrome. Case report. A 16-year-old boy with traumatic brain injury and seizures presented to the emergency department with facial swelling, rash, and back pain several days after increasing lamotrigine dose secondary to a breakthrough seizure. Creatinine, urine β2 microglobulin, and eosinophils were elevated. Antinuclear antibodies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme, and complement were normal. Renal biopsy showed acute granulomatous tubulointerstitial nephritis. Lamotrigine was discontinued, intravenous steroids were initiated, and the patient was discharged on Ativan and prednisone. Subsequently, he was diagnosed with bilateral anterior uveitis (vision 20/30 bilaterally) and started on prednisolone and cyclopentolate. Two months later, he developed a branch retinal artery occlusion in the right eye (vision 20/70) and bilateral ocular hypertension for which timolol-brimonidine and dorzolamide were added. Neuroimaging and hypercoagulability workup was unremarkable. Vision and intraocular pressure improved, while uveitis remained recalcitrant. Several months later, the patient developed central serous retinopathy in the right eye (vision 20/30). Prednisone was stopped but restarted due to methotrexate intolerance. A month later, he reported dizziness and was diagnosed with severe bilateral sensorineural hearing loss. Brain magnetic resonance imaging showed foci of perivascular, subcortical, and cochlear enhancement. Transtympanic Decadron injections and infliximab infusions were initiated. At the final visit, vision remained at 20/30 with trace anterior chamber reaction bilaterally while on timolol-brimonidine, dorzolamide, and prednisolone. An idiosyncratic drug reaction should be considered in the differential diagnosis of TINU-atypical Cogan syndrome.

[Non-identified antinuclear antibodies in systemic sclerosis].

PubMed

Margot, A; Smet, J; Soyfoo, S

Systemic sclerosis is a rare auto immune disease characterized by a local or diffuse skin condition and a variable visceral impairment. Anti nuclear antibodies (ANA) can be found in 95 % of patients. The most frequent are the anti topoisomerase 1 or anti Scl 70 and the anti-centromeres. Other antibodies have been reported but they are not conventionally sought in clinical practice. They are referred to as " non identified " ANA. To seek the " non identified " antibodies in patients with scleroderma at Erasme Hospital, to assess their prevalence in this cohort and to correlate their presence with the clinical characteristics. 89 patients out of the cohort of Erasme hospital patients with scleroderma have been looked at. Their clinical and biological data have been identified and a detection of antibodies have been performed by first an immonudot technique and second an EliA technique. 17 out of the 89 patients of our cohort had " non identified " ANA. Among them, antibodies in 11 patients have been identified by the immunodot, among which 7 anti-PmScl 75 and/or 100,3 RNA polymerase III and 1 antifibrillarin. The EliA technique identif ied antibodies in 10 patients among which 5 anti- PmScl, 2 anti RNA polymerase, 2 anti-fibrillarin and 1 anti-centromere. Auto antibodies other than the antitopoisomerase and anti-centromere have been found in patients with scleroderma in our cohort. Certain links exist between the presence of a given antibody and clinical features. We still have to define whether there exist other auto antibodies of which we still are unaware since in some patient no antibodies were detected.

Next-Generation Autoantibody Testing by Combination of Screening and Confirmation-the CytoBead® Technology.

PubMed

Sowa, Mandy; Hiemann, Rico; Schierack, Peter; Reinhold, Dirk; Conrad, Karsten; Roggenbuck, Dirk

2017-08-01

Occurrence of autoantibodies (autoAbs) is a hallmark of autoimmune diseases, and the analysis thereof is an essential part in the diagnosis of organ-specific autoimmune and systemic autoimmune rheumatic diseases (SARD), especially connective tissue diseases (CTDs). Due to the appearance of autoAb profiles in SARD patients and the complexity of the corresponding serological diagnosis, different diagnostic strategies have been suggested for appropriate autoAb testing. Thus, evolving assay techniques and the continuous discovery of novel autoantigens have greatly influenced the development of these strategies. Antinuclear antibody (ANA) analysis by indirect immunofluorescence (IIF) on tissue and later cellular substrates was one of the first tests introduced into clinical routine and is still an indispensable tool for CTD serology. Thus, screening for ANA by IIF is recommended to be followed by confirmatory testing of positive findings employing different assay techniques. Given the continuous growth in the demand for autoAb testing, IIF has been challenged as the standard method for ANA and other autoAb analyses due to lacking automation, standardization, modern data management, and human bias in IIF pattern interpretation. To address these limitations of autoAb testing, the CytoBead® technique has been introduced recently which enables automated interpretation of cell-based IIF and quantitative autoAb multiplexing by addressable microbead immunoassays in one reaction environment. Thus, autoAb screening and confirmatory testing can be combined for the first time. The present review discusses the history of autoAb assay techniques in this context and gives an overview and outlook of the recent progress in emerging technologies.

The Place of Nailfold Capillaroscopy Among Instrumental Methods for Assessment of Some Peripheral Ischaemic Syndromes in Rheumatology.

PubMed

Lambova, Sevdalina N

2016-01-01

Micro- and macrovascular pathology is a frequent finding in a number of common rheumatic diseases. Secondary Raynaud's phenomenon (RP) is among the most common symptoms in systemic sclerosis and several other systemic autoimmune diseases including a broad differential diagnosis. It should be also differential from other peripheral vascular syndromes such as embolism, thrombosis, etc., some of which lead to clinical manifestation of the blue toe syndrome. The current review discusses the instrumental methods for vascular assessments. Nailfold capillaroscopy is the only method among the imaging techniques that can be used for morphological assessment of the nutritive capillaries in the nailfold area. Laser-Doppler flowmetry and laser-Doppler imaging are methods for functional assessment of microcirculation, while thermography and plethysmography reflect both blood flow in peripheral arteries and microcirculation. Doppler ultrasound and angiography visualize peripheral arteries. The choice of the appropriate instrumental method is guided by the clinical presentation. The main role of capillaroscopy is to provide differential diagnosis between primary and secondary RP. In rheumatology, capillaroscopic changes in systemic sclerosis have been recently defined as diagnostic. The appearance of abnormal capillaroscopic pattern inherits high positive predictive value for the development of a connective tissue disease that is higher than the predictive value of antinuclear antibodies. In cases of abrupt onset of peripheral ischaemia, clinical signs of critical ischaemia, unilateral or lower limb involvement, Doppler ultrasound and angiography are indicated. The most common causes for such clinical picture that may be referred to rheumatologic consultation are the antiphospholipid syndrome, mimickers of vasculitides such as atherosclerosis with cholesterol emboli, and neoplasms.

Juvenile onset systemic sclerosis: a single center experience of 23 cases from Asia.

PubMed

Misra, Ramnath; Singh, Gurmeet; Aggarwal, Parshant; Aggarwal, Amita

2007-08-01

The aim of this paper was to study the spectrum of juvenile scleroderma (JSSc) seen at a tertiary care referral center in Asia. Retrospective analysis of case records of patients with systemic sclerosis, having age of onset less than 16 years and seen at our hospital from 1988 to 2004, was done. Patients with linear scleroderma and morphea were excluded. There were 23 patients (19 girls, 4 boys) with median age of onset of 12 years (range 5-16 years). The median age at presentation was 17 years (range 10-34 years). The median time from first symptoms to presentation was 4 years (range 0.2-26 years). Among these, 14 had diffuse systemic sclerosis (DSSc), while 9 had limited scleroderma (LSSc). The clinical features seen at presentation in patients were: Raynaud's phenomenon in 19, digital ulcers in 14, loss of finger tip pulp in 12, reflux in 8, dysphagia in 7, arthritis in 8, digital gangrene in 2, and pulmonary artery hypertension in 1. Antinuclear antibody was positive in 15 out of 18 patients tested. Interstitial lung disease was seen in 15 patients, 6 of whom had diffuse disease. The median skin score was 22 (range 7-48) . One patient died of primary pulmonary hypertension within 1 year of onset of symptoms. At a mean follow-up of 34 months, 14 patients were stable or had improvement in skin score or dyspnea on exertion. DSSc and LSSc in childhood have a clinical presentation similar to adult patients, with cardiopulmonary involvement being the major predictor of outcome. The short-term prognosis of JSSc is good.

[A case of systemic lupus erythematosus with pulmonary hypertension].

PubMed

Nakano, K; Tanaka, Y; Aso, M; Saito, K; Fujii, K; Takazawa, A; Ota, T

2000-06-01

A 15 year-old girl was admitted to the hospital because of fever, polyarthlargia, dry cough, dyspnea, butterfly rash and multiple oral aphthas. The diagnosis of systemic lupus erythematosus (SLE) was made based on renal disorders, pancytopenia, positive antinuclear antibody and positive for antibodies to double-stranded DNA. On admission, she developed progressive dyspnea with highly active SLE. The patient was complicated with both pulmonary hypertension (PH) and interstitial pneumonitis (IP), judging from increased pulmonary sound by an auscultation, interstitial shadows especially at bilateral lower lung and enlarged shadow of right atrium in a chest rentgenogram, ground glass pattern of bilateral middle to lower lung in a chest computed tomographic scan, increased pulmonary artery pressure, 53 mmHg, by an ultrasound cardiograph (UCG). Combination of methylprednisolone pulse therapy, cyclosporin A and plasma exchanges was effectively administered, which resulted in improvement of disease activity of SLE, IP and PH. However, two months later, although disease activity of SLE was completely reduced, recurrence of PH by UCG and multiple pulmonary embolism (PE) which was observed by a chest rentgenogram and a pulmonary blood flow scintigraphy was further complicated. Administration of cyclophosphamide pulse therapy and warfarin therapy improved both PE and PH. The patient had PH at the different clinical course of SLE; 1) PH maybe induced by severe IP at the active phase of SLE and 2) PH brought about from multiple PE at the inactive phase of SLE. Thus, the case is thought to be suggestive of elucidating the pathogenesis of PH of several systemic autoimmune diseases including SLE.

A case of radiation-induced generalized morphea with prominent mucin deposition and tenderness.

PubMed

Yanaba, Koichi; Umezawa, Yoshinori; Nakagawa, Hidemi

2015-05-10

Radiation-induced morphea is a rare complication of radiation therapy. The affected areas are generally restricted to the radiation field or to the nearby surrounding area. A 67-year-old Japanese woman with a history of right breast cancer followed by adjuvant radiotherapy was referred our hospital because of 7-year history of symmetrical indurated erythematous plaques on her trunk. Three months after completion of irradiation, erythematous plaques developed on her right chest and gradually spread accompanied tenderness. She did not have a history of trauma to her right chest. Laboratory testing was positive for antinuclear antibody test at 1: 640 but negative for anti-SS-A/B, anti-U1-RNP, anti-DNA, anti-Sm, anticentromere, anti-topoisomerase I antibodies, and Borrelia and cytomegalovirus infection. She had no Raynaud's phenomenon, sclerodactyly, or nail-fold bleeding. She did not have interstitial lung disease or other internal organ involvement. A biopsy specimen revealed reticular dermal fibrosis with thickened collagen bundles with superficial and deep perivascular infiltration of mononuclear cells. These findings were consistent with morphea. Furthermore, mucin deposition was present in the papillary dermis upon Alcian blue staining, which has been reported to be observed in generalized morphea. Consequently, a diagnosis of generalized morphea induced by radiotherapy was made. She had been treated with oral hydroxychloroquine sulfate, resulting in the resolution of tenderness but the erythematous plaques remained. To the best of our knowledge, this is the first report of radiation-induced generalized morphea with prominent mucin deposition. Hydroxychloroquine sulfate may be efficacious for radiation-induced morphea-associated tenderness.

Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

PubMed

Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

2014-12-01

The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. Copyright © 2014 Elsevier B.V. All rights reserved.

Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systematic literature review.

PubMed

Santana, Iuri Usêda; Dias, Blenda; Nunes, Eduardo Araújo Santana; Rocha, Francisco Airton Castro da; Silva, Francisco Saraiva; Santiago, Mittermayer Barreto

2015-06-01

Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection. To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles. The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test. In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin. Copyright © 2015 Elsevier Inc. All rights reserved.

Cognitive impairment in systemic lupus erythematosus women with elevated autoantibodies and normal single photon emission computerized tomography.

PubMed

Peretti, Charles-Siegfried; Peretti, Charles Roger; Kozora, Elizabeth; Papathanassiou, Dimitri; Chouinard, Virginie-Anne; Chouinard, Guy

2012-01-01

Systemic lupus erythematosus (SLE) is known to induce psychiatric disorders, from psychoses to maladaptive coping. Brain autoantibodies were proposed to explain SLE neuropsychiatric disorders and found to be elevated before the onset of clinical symptoms. We assessed cognition in Caucasian SLE women with elevated autoantibodies without overt neuropsychiatric syndromes, in conjunction with single photon emission computerized tomography (SPECT). 31 women meeting SLE criteria of the American College of Rheumatology (ACR) were included. Patients who met the ACR neuropsychiatric definition were excluded. Matched controls were 23 healthy women from the Champagne-Ardenne region, France. Participants completed neuropsychological and autoantibodies measurements, and 19 completed SPECT. 61% (19/31) of women with SLE and 53% (9/17) of those with normal SPECT had significant global cognitive impairment defined as 4 T-scores <40 in cognitive tests, compared to 0% (0/23) of controls. SLE women also had significantly greater cognitive dysfunction (mean T-score) on the Wechsler Adult Intelligence Scale (WAIS) visual backspan, Trail Making Test A and B, WAIS Digit Symbol Substitution Test and Stroop Interference, compared to controls. Elevated antinuclear antibody correlated with impairment in the WAIS visual span, WAIS visual backspan, and cancellation task; elevated anti-double-stranded DNA antibody and anticardiolipin correlated respectively with impairment in the Trail Making Test A and WAIS auditive backspan. Two SLE women had abnormal SPECT. A high prevalence of cognitive deficits was found in Caucasian SLE women compared to normal women, which included impairment in cognitive domains important for daily activities. Elevated autoantibodies tended to correlate with cognitive dysfunction. Copyright © 2012 S. Karger AG, Basel.

Low diagnostic and predictive value of anti-dsDNA antibodies in unselected patients with recent onset of rheumatic symptoms: results from a long-term follow-up Scandinavian multicentre study.

PubMed

Compagno, M; Jacobsen, S; Rekvig, O P; Truedsson, L; Heegaard, N H; Nossent, J; Jönsen, A; Jacobsen, R S; Eilertsen, G Ø; Sturfelt, G; Bengtsson, A A

2013-01-01

To verify the diagnostic accuracy of anti-double-stranded DNA (anti-dsDNA) antibodies detected by the Crithidia luciliae immunofluorescence test (CLIFT) in a cohort of unselected patients, referred to a rheumatologist due to recent onset of rheumatic symptoms. A total of 1073 consecutive patients were screened for anti-nuclear antibodies (ANAs). Serum samples from 292 ANA-positive and 292 matching ANA-negative patients were tested three times for anti-dsDNA antibodies, using two different CLIFT kits (ImmunoConcepts(®) and Euroimmun(®)). An initial clinical diagnosis was made by rheumatologists unaware of the results. The diagnoses were updated after a median follow-up of 4.8 years. CLIFT was positive at least once in 60 patients but only 23 patients were CLIFT positive in all of the assays. Diagnosis of systemic lupus erythematosus (SLE) was made initially in 65 patients, of whom 24 (37%) were CLIFT positive. Many other diagnoses were observed among the CLIFT-positive patients. Overall, 16 (5.5%) ANA-negative patients were CLIFT positive. After approximately 5 years, the diagnosis of SLE remained unchanged in 63 patients (23 CLIFT positive) and altered in only two (one CLIFT positive). Among the 36 CLIFT-positive patients who were not diagnosed with SLE at study entry, only one developed SLE during the follow-up period. CLIFT was not reliable as a diagnostic tool in unselected patients with rheumatic symptoms. ANAs were of little value as a screening test before the CLIFT analysis. CLIFT had surprisingly low positive predictive value (PPV) for the diagnosis of SLE despite its high specificity. For non-SLE patients, being CLIFT positive poses little risk of developing SLE within 5 years.

B cell autophagy mediates TLR7-dependent autoimmunity and inflammation.

PubMed

Weindel, Chi G; Richey, Lauren J; Bolland, Silvia; Mehta, Abhiruchi J; Kearney, John F; Huber, Brigitte T

2015-01-01

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease, defined by loss of B cell self-tolerance that results in production of antinuclear antibodies (ANA) and chronic inflammation. While the initiating events in lupus development are not well defined, overexpression of the RNA-recognizing toll-like receptor (TLR)7 has been linked to SLE in humans and mice. We postulated that autophagy plays an essential role in TLR7 activation of B cells for the induction of SLE by delivering RNA ligands to the endosomes, where this innate immune receptor resides. To test this hypothesis, we compared SLE development in Tlr7 transgenic (Tg) mice with or without B cell-specific ablation of autophagy (Cd19-Cre Atg5(f/f)). We observed that in the absence of B cell autophagy the 2 hallmarks of SLE, ANA and inflammation, were eliminated, thus curing these mice of lupus. This was also evident in the significantly extended survival of the autophagy-deficient mice compared to Tlr7.1 Tg mice. Furthermore, glomerulonephritis was ameliorated, and the serum levels of inflammatory cytokines in the knockout (KO) mice were indistinguishable from those of control mice. These data provide direct evidence that B cells require TLR7-dependent priming through an autophagy-dependent mechanism before autoimmunity is induced, thereafter involving many cell types. Surprisingly, hyper-IgM production persisted in Tlr7.1 Tg mice in the absence of autophagy, likely involving a different activation pathway than the production of autoantibodies. Furthermore, these mice still presented with anemia, but responded with a striking increase in extramedullary hematopoiesis (EMH), possibly due to the absence of pro-inflammatory cytokines.

New directions in the treatment of systemic lupus erythematosus.

PubMed

Kalunian, Kenneth; Merrill, Joan T

2009-06-01

The aim of this review is to provide an up-to-date overview of treatment approaches for systemic lupus erythematosus (SLE), highlighting the multiplicity and heterogeneity of clinical symptoms that underlie therapeutic decisions. Discussion will focus on the spectrum of currently available therapies, their mechanisms and associated side-effects. Finally, recent developments with biologic treatments including rituximab, epratuzumab, tumor necrosis factor (TNF) inhibitors, and belimumab, will be discussed. A MEDLINE literature search for 'systemic lupus erythematosus' and 'damage' and 'treatment' was undertaken for 1996-2008. Secondary citations were obtained from selected manuscripts. Individual case studies were excluded. SLE is an autoimmune disease involving multiple organ systems, a clinical pattern of flares and remissions, and the presence of anti-nuclear autoantibodies. Whereas early symptoms most frequently involve the skin and joints, disease morbidity and mortality are usually associated with cardiovascular events and damage to major organs, particularly the kidneys. Many of the current therapeutic options are considered to be inadequate because of toxicities, accrual of organ damage, and insufficient control of the underlying disease pathology. Improved understanding of SLE pathogenesis and immunology has led to the identification of new treatment targets. Current interest is mainly focused on the targeted immunosuppressive actions provided by biologic therapy. Although the potential long-term beneficial or harmful effects of the new molecular treatments are unclear, their precise molecular targeting may reveal key relationships within the immune system and advance the cause of individualized molecular medicine. Biologic compounds that target specific immunologic mechanisms offer a new paradigm in the treatment of SLE, one that may, at best, reverse the course of the disease and, at the very least, might provide some new alternatives to reduce symptoms and limit tissue damage without undue contribution to overall morbidity and mortality.

Nuclear fluorescence serum reactivity on monkey oesophagus: a new antibody for the follow-up of coeliac disease?

PubMed

Picarelli, A; Sabbatella, L; Di Tola, M; Silano, M; Nicolussi, A; D'Inzeo, S; Coppa, A

2010-09-01

We have identified previously a nuclear fluorescence reactivity (NFR) pattern on monkey oesophagus sections exposed to coeliac disease (CD) patients' sera positive for anti-endomysium antibodies (EMA). The aim of the present work was to characterize the NFR, study the time-course of NFR-positive results in relation to gluten withdrawal and evaluate the potential role of NFR in the follow-up of CD. Twenty untreated, 87 treated CD patients and 15 healthy controls were recruited and followed for 12 months. Their sera were incubated on monkey oesophagus sections to evaluate the presence of NFR by indirect immunofluorescence analysis. Duodenal mucosa samples from treated CD patients were challenged with gliadin peptides, and thus the occurrence of NFR in culture supernatants was assessed. The NFR immunoglobulins (Igs) reactivity with the nuclear extract of a human intestinal cell line was investigated. Serum NFR was present in all untreated CD patients, persisted up to 151 ± 37 days from gluten withdrawal and reappeared in treated CD patients under dietary transgressions. Serum NFR was also detected in two healthy controls. In culture supernatants of coeliac intestinal mucosa challenged with gliadin peptides, NFR appeared before EMA. The Igs responsible for NFR were identified as belonging to the IgA2 subclass. The NFR resulted differently from EMA and anti-nuclear antibodies, but reacted with two nuclear antigens of 65 and 49 kDa. A new autoantibody, named NFR related to CD, was described. Furthermore, NFR detection might become a valuable tool in monitoring adherence to a gluten-free diet and identifying slight dietary transgressions. © 2010 British Society for Immunology.

Neurological autoantibodies in drug-resistant epilepsy of unknown cause.

PubMed

Tecellioglu, Mehmet; Kamisli, Ozden; Kamisli, Suat; Yucel, Fatma Ebru; Ozcan, Cemal

2018-03-09

Autoimmune epilepsy is a rarely diagnosed condition. Recognition of the underlying autoimmune condition is important, as these patients can be resistant to antiepileptic drugs. To determine the autoimmune and oncological antibodies in adult drug-resistant epilepsy of unknown cause and identify the clinical, radiological, and EEG findings associated with these antibodies according to data in the literature. Eighty-two patients with drug-resistant epilepsy of unknown cause were prospectively identified. Clinical features were recorded. The levels of anti-voltage-gated potassium channel complex (anti-VGKCc), anti-thyroid peroxidase (anti-TPO), anti-nuclear antibody (ANA), anti-glutamic acid decarboxylase (anti-GAD), anti-phospholipid IgG and IgM, anti-cardiolipin IgG and IgM, and onconeural antibodies were determined. Serum antibody positivity suggesting the potential role of autoimmunity in the aetiology was present in 17 patients with resistant epilepsy (22.0%). Multiple antibodies were found in two patients (2.6%). One of these patients (1.3%) had anti-VGKCc and ANA, whereas another (1.3%) had anti-VGKCc and anti-TPO. A single antibody was present in 15 patients (19.5%). Of the 77 patients finally included in the study, 4 had anti-TPO (5.2%), 1 had anti-GAD (1.3%), 4 had anti-VGKCc (5.2%) 8 had ANA (10.3%), and 2 had onconeural antibodies (2.6%) (1 patient had anti-Yo and 1 had anti-MA2/TA). The other antibodies investigated were not detected. EEG abnormality (focal), focal seizure incidence, and frequent seizures were more common in antibody-positive patients. Autoimmune factors may be aetiologically relevant in patients with drug-resistant epilepsy of unknown cause, especially if focal seizures are present together with focal EEG abnormality and frequent seizures.

Prevalence of anti-DFS70 antibodies in patients with and without systemic autoimmune rheumatic diseases.

PubMed

Shovman, Ora; Gilburd, Boris; Chayat, Chen; Amital, Howard; Langevitz, Pnina; Watad, Abdulla; Guy, Adi; Perez, Dolores; Azoulay, Danielle; Blank, Miri; Segal, Yael; Bentow, Chelsea; Mahler, Michael; Shoenfeld, Yehuda

2018-01-01

Autoantibodies to the dense fine speckled 70 (DFS70) antigen are common among antinuclear antibodies (ANA) positive healthy individuals (HI). We assessed the prevalence of anti-DFS70 antibodies in patients with and without ANA-associated rheumatic diseases (AARDs) by two methods: chemiluminescent immunoassay (CIA) and an indirect immunofluorescence (IIF) assay based on immunoadsorption for DFS70. Fifty-one ANA-positive sera samples from patients with confirmed clinical diagnosis of AARD, 92 samples from HI and 85 samples submitted to a reference laboratory for routine ANA testing were evaluated for the presence of anti-DFS70 antibodies. The samples were evaluated by QUANTA Flash DFS70 CIA using BIO-FLASH instrument and by NOVA Lite selected HEp-2 kit on NOVA View - an automated IIF system. Sera with DFS positive pattern were pre-absorbed with highly purified human DFS70 antigen, and then tested again. Twenty-four samples (10.5%) tested by QUANTA Flash DFS70 CIA were positive for anti-DFS70 antibodies. The prevalence of monospecific anti-DFS70 antibodies was significantly higher in healthy subjects than in patients with AARDs (10.9% vs. 1.9%, p=0.02). The frequency of anti-DFS70 antibodies in samples submitted for routine ANA testing was 15.2%. A very good agreement was found between CIA and the DFS pattern identified by the automated HEp-2 IIF (kappa=0.97). In 80% of the samples obtained from patients without AARDs, immunoadsorption effectively inhibited the anti-DFS70 antibodies. The data confirm that mono-specific anti-DFS70 antibodies are a strong discriminator between ANA positive HI and AARD patients, and their evaluation should be included in ANA testing algorithms.

IgG4-Related Sclerosing Disease, an Emerging Entity: A Review of a Multi-System Disease

PubMed Central

Divatia, Mukul; Kim, Sun A

2012-01-01

Immunoglobulin G4-related systemic disease (IgG4-RSD) is a recently defined emerging entity characterized by a diffuse or mass forming inflammatory reaction rich in IgG4-positive plasma cells associated with fibrosclerosis and obliterative phlebitis. IgG4-RSD usually affects middle aged and elderly patients, with a male predominance. It is associated with an elevated serum titer of IgG4, which acts as a marker for this recently characterized entity. The prototype is IgG4-related sclerosing pancreatitis or autoimmune pancreatitis (AIP). Other common sites of involvement are the hepatobiliary tract, salivary gland, orbit, and lymph node, however practically any organ can be involved, including upper aerodigestive tract, lung, aorta, mediastinum, retroperitoneum, soft tissue, skin, central nervous system, breast, kidney, and prostate. Fever or constitutional symptoms usually do not comprise part of the clinical picture. Laboratory findings detected include raised serum globulin, IgG and IgG4. An association with autoantibody detection (such as antinuclear antibodies and rheumatoid factor) is seen in some cases. Steroid therapy comprises the mainstay of treatment. Disease progression with involvement of multiple organ-sites may be encountered in a subset of cases and may follow a relapsing-remitting course. The principal histopathologic findings in several extranodal sites include lymphoplasmacytic infiltration, lymphoid follicle formation, sclerosis and obliterative phlebitis, along with atrophy and destruction of tissues. Immunohistochemical staining shows increased IgG4+ cells in the involved tissues (>50 per high-power field, with IgG4/IgG ratio >40%). IgG4-RSD may potentially be rarely associated with the development of lymphoma and carcinoma. However, the nature and pathogenesis of IgG4-RSD are yet to be fully elucidated and provide immense scope for further studies. PMID:22187229

Clinical Profile of Levamisole-Adulterated Cocaine-Induced Vasculitis/Vasculopathy: A 30-Case Series.

PubMed

Muñoz-Vahos, Carlos Horacio; Herrera-Uribe, Sebastián; Arbeláez-Cortés, Álvaro; Jaramillo-Arroyave, Daniel; González-Naranjo, Luis Alonso; Vásquez-Duque, Gloria; Restrepo-Escobar, Mauricio; Correa-Londoño, Luis Alfonso; Arias-Restrepo, Luis Fernando; Vanegas-García, Adriana Lucía

2018-05-19

The aims of this study were to describe clinical and laboratory manifestations of patients with levamisole-adulterated cocaine-induced vasculitis/vasculopathy and to propose a skin classification according to the distribution and severity of lesions. We report the characteristics of 30 patients admitted with levamisole-adulterated cocaine-induced vasculitis/vasculopathy in 4 high-complexity institutions in Colombia, from December 2010 to May 2017. We compare our findings with the principal published series. Median age was 31 years (interquartile range, 27-38 years) with a male-to-female ratio of 5:1. Eighty-three percent of the patients had retiform purpura affecting the limbs, buttocks, face, or abdomen; 73% had ear necrosis, 50% cutaneous ulcers, 17% genital necrosis, 13% oral ulcers, and 10% digital necrosis. Cutaneous involvement was classified according to the frequency of the compromised corporal area, and purpuric lesions were stratified in 4 grades of severity. Anti-neutrophil cytoplasmic autoantibodies were positive in 85% of the cases, lupus anticoagulant in 73%, and antinuclear autoantibodies in 57%, and rheumatoid factor was negative in all cases. We found nephritis in 17 cases (57%). Prednisolone was used in most of the patients (70%), with other immunosuppressive agents being used in a lower percentage. Improvement was observed in 93% of the patients, but symptoms recurred in 40%, attributed to relapses in consumption. End-stage chronic renal disease developed in 10% of the cases, and 1 patient died. Because of rising cocaine consumption and levamisole adulteration frequency, levamisole-adulterated cocaine-induced vasculitis/vasculopathy is becoming more common. Detailed characterization of skin involvement coupled with multiple antibody positivity is essential for a diagnosis. Renal involvement is frequent, clinically and histologically heterogeneous, and potentially serious.

Clinical and immunological manifestations in 151 SLE patients living in Dubai.

PubMed

AlSaleh, J; Jassim, V; ElSayed, M; Saleh, N; Harb, D

2008-01-01

To gain better understanding of systemic lupus erythematosus (SLE) in Dubai we studied the clinical and immunological manifestations in a cohort of 151 patients attended Rheumatology Clinic in Dubai Hospital between January 2002 and January 2007. We found that the female to male ratio was 20.5:1, with a mean age of 35.5 years (0.9). The mean age at disease onset was 28.9 years (0.8) and mean disease duration 6.7 years (0.4). Five-year survival rate in our cohort was 94%. The commonest clinical manifestations in this cohort were arthritis (88%), haematological abnormalities (61.6%), and malar rash (60.3%). Leucopenia, fever, hair loss and proteinuria were observed in approximately half of the patients. Anaemia was found in 44.3% but only 9.9% had haemolytic anaemia. Photosensitive rash was seen in 43% of patients. Approximately one-third of the patients had serositis and mouth ulcers, 30.5 and 27.2% respectively. Vasculitis was observed in 19.2% of patients. Neuropsychiatric manifestations (15.9%), discoid lupus lesions (12.6%), and brain infarcts (13.2%) were infrequent. Subacute cutaneous lupus (6%) was also uncommon. Anti-nuclear antibodies were detected in 98%, anti-double stranded DNA antibodies in 88.7%, anti-Sm antibodies in 19.7%, anti-RNP in 40.4%, anti-Ro antibodies in 52.3% and anti-La antibodies in 19.8%. Anti-cardiolipin IgM and IgG were detected in 25.3 and 22.4%, respectively. This study suggests that Arabs with SLE residing in Dubai have comparable clinical features to their counterparts in other Arab countries and Western countries. The high prevalence of positive anti-Ro antibodies among our Arab patients probably reflects a character, that is, commonly seen in SLE patients of Middle East origin.