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1

Sarcoidosis presenting as antinuclear antibody positive glomerulonephritis.  

PubMed Central

A 43 year old woman who initially presented with the nephrotic syndrome, glomerulonephritis, and antinuclear antibodies (ANAs) was given the diagnosis of systemic lupus erythematosus (SLE). One year later the patient developed progressive subcutaneous nodules on her forearms, with histopathology of non-caseating granulomas. Further evaluation of the patient showed mediastinal lymphadenopathy and interstitial lung disease with numerous granulomas, establishing the diagnosis of sarcoidosis. The presence of autoimmune antibodies and glomerulonephritis has been reported in sarcoidosis, but this case is believed to be the first in which both glomerulonephritis and ANAs are present in a sarcoid patient.

Soto-Aguilar, M C; Boulware, D W

1988-01-01

2

Hypertrophic pulmonary osteoarthropathy with positive antinuclear antibodies: case report.  

PubMed

A male Afro-descendant patient, 57 years old, complaining of polyarticular involvement and weight loss for 18 months, with a load of 13.5 pack years of smoking. On physical examination there was pain on palpation of the right knee and right leg, with signs of inflammation on the knee. We also observed digital clubbing in all fingers. Antinuclear antibodies (ANA) and anti-Sm antibodies were positive. X-rays of the legs and arm showed cortical thickening of long bones. The computed tomography demonstrated a large mass located in the middle lobe of the right lung. The anatomopathological study revealed a bronchial adenocarcinoma. The history of polyarticular involvement associated with positive anti-Sm and ANA antibodies could lead to an erroneous diagnosis of systemic lupus erythematosus. Considering the bad consequences of delayed diagnosis in this patient, the medical team should be alerted for suspecting and look for a lung cancer under these circumstances. PMID:22740821

Cruz, C; Rocha, M; Andrade, D; Guimarães, F; Silva, V; Souza, S; Moura, C A; Moura, C G

2012-05-01

3

Hypertrophic Pulmonary Osteoarthropathy with Positive Antinuclear Antibodies: Case Report  

PubMed Central

A male Afro-descendant patient, 57 years old, complaining of polyarticular involvement and weight loss for 18 months, with a load of 13.5 pack years of smoking. On physical examination there was pain on palpation of the right knee and right leg, with signs of inflammation on the knee. We also observed digital clubbing in all fingers. Antinuclear antibodies (ANA) and anti-Sm antibodies were positive. X-rays of the legs and arm showed cortical thickening of long bones. The computed tomography demonstrated a large mass located in the middle lobe of the right lung. The anatomopathological study revealed a bronchial adenocarcinoma. The history of polyarticular involvement associated with positive anti-Sm and ANA antibodies could lead to an erroneous diagnosis of systemic lupus erythematosus. Considering the bad consequences of delayed diagnosis in this patient, the medical team should be alerted for suspecting and look for a lung cancer under these circumstances.

Cruz, C.; Rocha, M.; Andrade, D.; Guimaraes, F.; Silva, V.; Souza, S.; Moura, C.A.; Moura, C.G.

2012-01-01

4

Antinuclear antibodies in dogs with leishmaniasis.  

PubMed

An indirect immunofluorescence method using rat liver as material was developed to determine the incidence of antinuclear antibodies in serum from 44 adult dogs naturally infected with leishmaniasis and, for comparative purposes, in a control group of 30 healthy dogs. Animals in both groups were of different breeds with a similar age distribution. Antinuclear antibodies were not detected in the healthy dogs and only 15.9% of the diseased dogs, 12.0% males and 21.1% females, were positive. The results indicate that in contrast to previously reported figures, the incidence of antinuclear antibodies is low in canine leishmaniasis at least when diagnosis is first made. In order to investigate whether antinuclear antibodies may play a role in the development of the renal damage observed in canine leishmaniasis, the concentrations of serum creatinine were related to the presence of antinuclear antibodies. Only 28.5% of the antinuclear antibodies positive infected dogs showed hypercreatininemia as did 32.4% of the antinuclear antibodies negative infected dogs. Thus, antinuclear antibodies are not significantly cause-effect related to the development of the renal lesions seen in canine leishmaniasis. PMID:8767735

Lucena, R; Ginel, P J; Lopez, R; Novales, M; Martin, E; Molleda, J M

1996-06-01

5

Antinuclear antibodies (ANA) in chronic hepatitis C virus infection: correlates of positivity and clinical relevance.  

PubMed

We examined correlates of antinuclear antibody (ANA) positivity (ANA+) in individuals with chronic hepatitis C virus (HCV) infection and the effect of positivity on clinical outcome of HCV. Pretreatment sera from 645 patients from three centres in Sweden (n = 225), the UK (n = 207) and Italy (n = 213) were evaluated by indirect immunofluorescence on Hep-2 cells for ANA pattern and titre by a single laboratory. Liver biopsies were all scored by one pathologist. A total of 258 patients were subsequently treated with interferon monotherapy. There was a significant difference in the prevalence of ANA (1:40) by geographic location: Lund 4.4%, London 8.7%, Padova 10.3% [odds ratio (OR) = 0.66; 95% CI: 0.46-0.94; P = 0.023]. Duration of HCV infection, age at infection, current age, route of infection, viral genotype, alcohol consumption, fibrosis stage and inflammatory score were not correlated with ANA+ or ANA pattern. Female gender was correlated with ANA+ and this association persisted in multivariable analyses (OR = 3.0; P = 0.002). Increased plasma cells were observed in the liver biopsies of ANA-positive individuals compared with ANA-negative individuals, while a trend towards decreased lymphoid aggregates was observed [hazard ratio (HR) = 9.0, P = 0.037; HR = 0.291, P = 0.118, respectively]. No correlations were observed between ANA positivity and nonresponse to therapy (OR = 1.4; P = 0.513), although ANA+ was correlated with faster rates of liver fibrosis, this was not statistically significant (OR = 1.8; P = 0.1452). Low titre ANA+ should not be a contraindication for interferon treatment. Our observation of increased plasma cells in ANA+ biopsies might suggest B-cell polyclonal activity with a secondary clinical manifestation of increased serum immunoglobulins. PMID:15357653

Yee, L J; Kelleher, P; Goldin, R D; Marshall, S; Thomas, H C; Alberti, A; Chiaramonte, M; Braconier, J-H; Hall, A J; Thursz, M R

2004-09-01

6

Antinuclear Antibodies (ANA)  

MedlinePLUS

... itself which can lead to autoimmune diseases, including lupus , scleroderma , Sjögren's syndrome , polymyositis/ dermatomyositis, mixed connective tissue disease, drug-induced lupus, and autoimmune hepatitis. A positive ANA can also ...

7

Clinical and Serological Features of Patients Referred through a Rheumatology Triage System because of Positive Antinuclear Antibodies  

PubMed Central

Background The referral of patients with positive anti-nuclear antibody (ANA) tests has been criticized as an inappropriate use of medical resources. The utility of a positive ANA test in a central triage (CT) system was studied by determining the autoantibody profiles and clinical diagnoses of patients referred to rheumatologists through a CT system because of a positive ANA test. Methods Patients that met three criteria were included: (1) referred to Rheumatology CT over a three year interval; (2) reason for referral was a “positive ANA”; (3) were evaluated by a certified rheumatologist. The CT clinical database was used to obtain demographic and clinical information and a serological database was used to retrieve specific ANA and/or extractable nuclear antigen (ENA) test results. Clinical information was extracted from the consulting rheumatologist's report. Results 15,357 patients were referred through the CT system; 643 (4.1%) of these because of a positive ANA and of these 263 (40.9%) were evaluated by a certified rheumatologist. In 63/263 (24%) of ANA positive patients, the specialist provided a diagnosis of an ANA associated rheumatic disease (AARD) while 69 (26.2%) had no evidence of any disease; 102 (38.8%) had other rheumatologic diagnoses and 29 (11%) had conditions that did not meet AARD classification criteria. Of ANA positive archived sera, 15.1% were anti-DFS70 positive and 91.2% of these did not have an AARD. Conclusions This is the first study to evaluate the serological and clinical features of patients referred through a CT system because of a positive ANA. The spectrum of autoantibody specificities was wide with anti-Ro52/TRIM21 being the most common autoantibody detected. Approximately 15% of referrals had only antibodies to DFS70, the vast majority of which did not have clinical evidence for an AARD. These findings provide insight into the utility of autoantibody testing in a CT system.

Fitch-Rogalsky, Christie; Steber, Whitney; Mahler, Michael; Lupton, Terri; Martin, Liam; Barr, Susan G.; Mosher, Dianne P.; Wick, James; Fritzler, Marvin J.

2014-01-01

8

Hydroxychloroquine is a good second-line treatment for adults with immune thrombocytopenia and positive antinuclear antibodies.  

PubMed

Treatment of patients with lupus-associated thrombocytopenia (SLE-ITP) is not standardized. We report data on efficacy and safety of hydroxychloroquine (HCQ) in this setting and in ITP patients with positive antinuclear antibodies (ANA) without definite SLE. Inclusion criteria were: definite diagnosis of ITP with a platelet count (PLT) <50 × 10(9) /L, ANA ? 1/160 on Hep2 cells with or without a definite diagnosis of SLE, and no sustained response to at least one previous treatment-line and treatment with HCQ. Response criteria were Complete Response (CR) for PLT ? 100 × 10(9) /L and Response (R) for PLT ?30 × 10(9) /L and at least twice the initial value. Forty patients (32 females) with a mean age of 35 ± 17 years and PLT at ITP diagnosis of 14 ± 13 × 10(9) /L were analyzed. Twelve (30%) patients had a SLE-ITP, 28 patients had only positive ANA. All the patients failed to respond to oral prednisone with a median of two treatment-lines (1-5) before HCQ which was initially given in combination with another ITP treatment in 36 patients. Overall response rate was 60% (24/40) including 18 lasting CR and six lasting R maintained with a median follow-up of 64 months (6-146), in ¾ of cases with only HCQ and no concomitant ITP treatment. The response rate (CR+R) was higher in the SLE group vs ANA-positive group (83% vs 50%, P < 0.05). No patient stopped HCQ because of a side-effect. HCQ appears to be a safe and effective second line treatment for patients with SLE-ITP or ITP and high titer of ANA. This trial was registered at www.clinicaltrials.gov as # NCT01549184. PMID:24254965

Khellaf, Mehdi; Chabrol, Amèlie; Mahevas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

2014-02-01

9

Anti-nuclear antibodies positive serum from systemic lupus erythematosus patients promotes cardiovascular manifestations and the presence of human antibody in the brain  

PubMed Central

Background: Systemic lupus erythematosus (SLE) is characterized by the presence of anti-nuclear antibodies (ANAs) in the serum of patients. These antibodies may cross over into the brain resulting in the development of neuropsychiatric symptoms and result in abnormal pathology in other organs such as the heart and kidneys. Objective: The objective of this study was to determine if SLE pathology could be detected in the hearts and brains of rats injected with positive human ANA serum. Materials and Methods: Lewis rats (n = 31) were selected for this study due to documented research already performed with this strain in the investigation of serum sickness, encephalitis and autoimmune related carditis. Rats were injected once a week with either ANA positive or negative control serum or saline. Hearts were examined for initial signs of heart disease including the presence of lipid deposits, vegetation, increased ventricular thickness and a change in heart weight. Brains were examined for the presence of human antibody and necrotic lesions. Animals were observed for outward signs of neuropathy as well. Blood samples were taken in order to determine final circulating concentrations of IgG and monitor histamine levels. Results: Animals injected with ANA were significantly higher for lipid deposits in the heart and an increased ventricular thickness was noted. One animal even displayed Libman-Sacks endocarditis. Brains were positive for the presence of human IgG and diffuse internal lesions occurred in 80% of the ANA positive serum injected animals examined. Blood histamine levels were not significantly different, but actually lower than controls by the end of the experiment. Conclusion: Since human antibodies were detected in the brain, further studies will have to identify which antibody cross reactions are occurring within the brain, examine cell infiltration as well as characterize the antibodies associated with more destructive consequences such as lesion formation.

Kelly-Worden, Marie; Hammer, Leslie; Gebhard, Robyn; Schrader, Lauran; Griffin, Marley; Cooper, Dalahnna

2014-01-01

10

Anti-nuclear antibodies in patients with premature ovarian failure  

Microsoft Academic Search

We examined the prevalence of anti-nuclear antibodies (ANA) in 32 consecutive patients with premature ovarian failure with and without chromosomal abnormalities. Blood samples were taken for karyotype determination as well as detection of autoantibodies, X-terminal microdeletions and spontaneous follicular growth. The correlation between ANA positivity and the age at onset of amenorrhoea, as well as the presence of karyotype abnormalities,

B. Ishizuka; Y. Kudo; A. Amemiya; H. Yamada; T. Matsuda; T. Ogata

1999-01-01

11

Antinuclear antibodies in arthritic and nonarthritic children with uveitis.  

PubMed

We determined whether a positive test for antinuclear antibodies correlated with uveitis only in children with juvenile rheumatoid arthritis (JRA) or whether they also represented a serologic marker for isolated idiopathic chronic uveitis in children. We conclude that the immunopathogenesis of uveitis associated with JRA is different from that of idiopathic chronic uveitis. PMID:2313675

Rosenberg, A M; Romanchuk, K G

1990-01-01

12

Circulating Antinuclear Antibody and Rheumatoid Factor in Coal Pneumoconiosis  

PubMed Central

Circulating antinuclear antibody and rheumatoid factor have been measured in 109 coal miners with pneumoconiosis whose chest radiograph showed a range of abnormalities varying from simple pneumoconiosis of mild degree to advanced progressive massive fibrosis. At a screening dilution of 1/10 the overall incidence of antinuclear antibody was 17%. In almost half of the positive cases the titre was 1/40 or greater. The prevalence of antinuclear antibody was lowest in those with simple pneumoconiosis (9%) and highest in those with category C progressive massive fibrosis (27%). A similar but less striking trend was seen with rheumatoid factor, ranging from 6% in simple pneumoconiosis to 18% in category C progressive massive fibrosis. The trend of increasing frequency of autoantibodies with advancing radiographic category was most marked when the frequencies of antinuclear antibody and rheumatoid factor were combined. These autoantibodies were found in 13% of the miners with simple pneumoconiosis and 45% of those with category C progressive massive fibrosis (P for the trend=0·01).

Soutar, C. A.; Turner-Warwick, Margaret; Parkes, W. Raymond

1974-01-01

13

Anti-ssDNA and antinuclear antibodies in human malaria.  

PubMed Central

The incidence of serum antinuclear antibodies and serum antibodies to single stranded (ss) and double stranded (ds) DNA was investigated following acute malaria in 58 Caucasians visiting tropical countries but resident in Britain and in 24 Ghanaians resident in Ghana. In Caucasians this infection was associated with a significant increase in the incidence of speckled antinuclear antibodies (38% compared to 3% in controls; P less than 0.001) and a significant rise in antibody levels against ssDNA (14% compared to 5%; P less than 0.05), but no rise in antibodies against dsDNA. Acute malaria in Ghanaians was associated with an incidence of 25% of antinuclear antibodies and 4% of antibodies to ssDNA; these were similar to those found in healthy Ghanaians who are chronically exposed to malaria. Antibodies against dsDNA were not detected. The incidence of antinuclear antibodies and levels of anti-ssDNA antibodies was higher in the Ghanaian healthy population than in normal Caucasians. These observations indicate that malaria is associated with the development of antinuclear and anti-ssDNA antibodies. Ghanaian patients with a tropical splenomegaly syndrome or with a nephrotic syndrome, both of which conditions are suspected of having a malarial aetiology, had serum levels of anti-ssDNA higher than healthy controls. This observation adds further circumstantial evidence to the role of malaria in causing anti-DNA antibodies.

Adu, D; Williams, D G; Quakyi, I A; Voller, A; Anim-Addo, Y; Bruce-Tagoe, A A; Johnson, G D; Holborow, E J

1982-01-01

14

In vivo antinuclear antibody of the skin: diagnostic significance and association with selective antinuclear antibodies.  

PubMed Central

Immunofluorescence microscopy of the skin has disclosed antibodies bound to epidermal cell nuclei in several connective tissue disorders. To establish the diagnostic potential of this phenomenon the results of immunofluorescence microscopy of biopsy specimens from 1651 subjects with various diseases and from 315 patients with systemic connective tissue disorders and related diseases were reviewed. It was found that the predictive value of the phenomenon for the presence of a systemic connective tissue disorder was, in general, 88%. Except for the homogeneous and thready patterns, which seldom appear, but are specific for SLE, in vivo antinuclear antibody (ANA) does not discriminate better between the various disorders than do serum antibodies. The presence of in vivo ANA in the skin was related to serum antibodies against non-histone nucleoproteins, but not to anti-dsDNA antibodies. Combined with the finding that antibodies against non-histone nucleoproteins can bind on the surface of human keratinocytes, this suggests that ANA of the skin occurs in vivo. Images

Velthuis, P J; Kater, L; van der Tweel, I; Meyling, F G; Derksen, R H; Hene, R J; van Geutselaar, J A; Baart de la Faille, H

1990-01-01

15

High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity  

PubMed Central

Background. Antinuclear antibodies (ANA) are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD) are frequently associated with other organ- and non-organ-specific autoimmune disorders. Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations. Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves' disease). ANA, anti-double DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire. Results. ANA positivity was found in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF in 3/93 (3.2%), and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%. Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.

Segni, Maria; Pucarelli, Ida; Truglia, Simona; Turriziani, Ilaria; Serafinelli, Chiara; Conti, Fabrizio

2014-01-01

16

Detection of antibodies to extractable nuclear antigens using calf thymus and rabbit thymus. A comparative study of 1000 consecutive anti-nuclear antibody positive patients.  

PubMed

A comparison between calf thymus extract and rabbit thymus extract to determine their suitability for clinical laboratories in detecting antibodies to extractable nuclear antigens (ENA) was undertaken. Calf thymus extract (CTE) detected 90% more ENA positive patients and 155% more lines than rabbit thymus extract (RTE). In contrast to RTE, CTE resolved Sm and RNP into two distinct lines, had superior stability at -80 degrees C and produced greater clarity of definition of precipitin lines. PMID:2492583

Collins, R J; Neil, J C; Druery, L N; Wilson, R J

1989-01-01

17

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

PubMed Central

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.

Bohnhorst, J ?vreb?; Hanssen, I; Moen, T

2001-01-01

18

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

PubMed

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

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

2014-03-01

19

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

PubMed Central

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.

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

2014-01-01

20

An Antinuclear Antibody-Negative Patient With Lupus Nephritis  

PubMed Central

Systemic lupus erythematosus (SLE) is a typical autoimmune disease that's characterized by various autoantibodies to nuclear and cytoplasmic antigens. The presence of antinuclear antibodies (ANA) in serum is generally considered a decisive diagnostic sign of SLE. However, a small subset of SLE patients who had the typical clinical features of SLE was reported to show persistently negative ANA tests. Our report describes a 16-yr-old female who presented with the clinical manifestations of SLE such as malar rash, photosensitivity, arthritis, lymphopenia, pericarditis and proteinuria. The serum autoantibodies were all negative and renal biopsy showed that the histopathological changes of immune complex mediated the focal segmental necrotizing glomerulonephritis with crescent formation. She was treated with monthly pulse cyclophosphamide along with corticosteroids. During the 2-yr follow-up period, the proteinuria was markedly decreased and all of the ANA and anti-double stranded DNA antibody tests were negative. This case suggests that ANA may not be required in the pathogenesis of lupus nephritis.

Kim, Hyoun-Ah; Chung, Jae-Wook; Park, Han-Jung; Joe, Dai-Yeol; Yim, Hyun-Ee; Park, Hae-Sim

2009-01-01

21

Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited  

PubMed Central

It has been more than 50 years since antinuclear antibodies were first discovered and found to be associated with connective tissue diseases. Since then different methods have been described and used for their detection or confirmation. For many decades immunofluorescent antinuclear antibody test has been the "gold standard" in the diagnosis of these disorders. However to increase the sensitivity and specificity of antinuclear antibody detection further approaches were explored. Today a battery of newer techniques are available some of which are now considered better and are competing with the older methods. This article provides an overview on advancement in antinuclear antibody detection methods, their future prospects, advantages, disadvantages and guidelines for use of these tests.

Kumar, Yashwant; Bhatia, Alka; Minz, Ranjana Walker

2009-01-01

22

Antinuclear antibody detection by automated multiplex immunoassay in untreated patients at the time of diagnosis.  

PubMed

Fully automated multiplex immunoassays are increasingly used as first line screening for antinuclear antibodies. The diagnostic performance of such multiplex assays in untreated patients at the time of diagnosis has not been reported. Antinuclear antibodies were measured by indirect immunofluorescence (IIF) (dilution 1:160) and by BioPlex 2200 ANA screen (antibodies to dsDNA, chromatin, ribosomal protein, SSA-52, SSA-60, SSB, Sm, SmRNP, RNP-A, RNP-68, Scl-70, Jo-1, and centromere B) in 236 patients with a systemic rheumatic disease at the time of diagnosis, 149 blood donors, 139 patients with chronic fatigue syndrome (CFS), and 134 diseased controls. BioPlex ANA screen and IIF were positive in, respectively, 79% and 90% of patients with systemic lupus erythematosus (SLE), 60% and 60% with cutaneous lupus, 72% and 93% with systemic sclerosis (SSc), 100% and 100% with mixed connective tissue disease (MCTD), 89% and 56% with primary Sjögren's (SS) syndrome, 36% and 36% with polymyositis/dermatomyositis, 5.4% and 6% of blood donors, 7.2% and 3.6% of patients with CFS, and 11% and 18% of diseased controls. BioPlex test result interval specific likelihood ratios increased with increasing antibody concentration. The simultaneous presence of at least three antibodies by BioPlex was found in 35% of patients with SLE, 4% with SSc, 100% with MCTD, 64% with SS, 7% with inflammatory myopathy, 0.7% of CFS and diseased controls, and none of the blood donors. In conclusion, test result specific likelihood ratios and the presence of multiple autoantibodies help with the interpretation of data generated by multiplex immunoassays. PMID:22387973

Op De Beéck, Katrijn; Vermeersch, Pieter; Verschueren, Patrick; Westhovens, René; Mariën, Godelieve; Blockmans, Daniel; Bossuyt, Xavier

2012-12-01

23

Human peripheral blood monocytes display surface antigens recognized by monoclonal antinuclear antibodies  

SciTech Connect

The authors used monoclonal anti-nuclear autoantibodies and indirect immunofluorescence to examine normal human peripheral blood mononuclear leukocytes for the presence of cell surface nuclear antigens. Only one monoclonal anti-histone antibody (MH-2) was found to bind to freshly isolated PBL, staining approximately 10% of large cells. However, after cells were placed into culture for 16-24 h, a high percentage (up to 60%) of large-sized cells were recognized by an anti-DNA (BWD-1) and several different antihistone monoclonal antibodies (BWH-1, MH-1, and MH-2). These antibodies recognize separate antigenic determinants on chromatin and histones extracted from chromatin. The histone antigen-positive cells were viable, and the monoclonal antibodies could be shown to be binding to the cell surface and not to the nucleus. Using monoclonal antibodies specific for monocytes and T cells, and complement-mediated cytotoxicity, the cells bearing histone antigens were shown to be primarily monocytes. The appearance of histone and DNA antigen-positive cells was nearly completely inhibited by the addition of low concentrations of cycloheximide at initiation of the cultures. In contrast, little effect on the percentage of positive cells was detected if cells were exposed to high doses of gamma irradiation before culture. These data further support the existence of cell surface nuclear antigens on selected cell subsets, which may provide insight into the immunopathogenesis of systemic lupus erythematosus and related autoimmune diseases.

Holers, V.M.; Kotzin, B.L.

1985-09-01

24

Anti-proteasome autoantibodies contribute to anti-nuclear antibody patterns on human larynx carcinoma cells  

Microsoft Academic Search

Background: Autoantibodies to the 20S proteasome represent an unspecific but common serological phenomenon in patients with systemic autoimmune diseases. Interestingly, a high prevalence of these antibodies have been observed in patients with connective tissue diseases, where anti-nuclear antibodies (ANAs) serve as an important diagnostic screening test.Objective: To disclose interference of anti-proteasome antibodies with known ANA patterns.Methods: Anti-proteasome antibodies were isolated

E Feist; M Brychcy; G Hausdorf; B Hoyer; K Egerer; T Do?rner; U Kuckelkorn; G-R Burmester

2007-01-01

25

Antinuclear antibodies recognize cellular autoantigens driven by apoptosis  

Microsoft Academic Search

Objectives. – Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis.Materials and methods. – HEp-2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL and Bax expression monitored apoptosis. Autoantigens were probed by indirect immunofluorescence and Western blot with autoantibodies or monoclonals against: DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase I,

Roxana Ramírez-Sandoval; Sergio H. Sánchez-Rodríguez; David Herrera-van Oostdam; Esperanza Avalos-Díaz; Rafael Herrera-Esparza

2003-01-01

26

Antinuclear antibodies recognize cellular autoantigens driven by apoptosis  

Microsoft Academic Search

Objectives. - Present study addresses the issue whether cellular antigens recognised by antinuclear autoantibodies are driven by apoptosis. Materials and methods. - HEp-2 cells were committed to apoptosis by camptothecin; DNA fragmentation and FasL and Bax expression monitored apoptosis. Autoantigens were probed by indirect immunofluorescence and Western blot with autoantibodies or monoclonals against: DNA, Ro60, La, U1-RNP, CENP-B, DNA Topoisomerase

Roxana Ramírez-Sandoval; Sergio H. Sánchez-Rodríguez; David Herrera-van Oostdam; Esperanza Avalos-Díaz; Rafael Herrera-Esparza

2003-01-01

27

Antinuclear antibodies in patients with Raynaud's phenomenon: clinical significance of anticentromere antibodies.  

PubMed Central

Antinuclear antibodies (ANA) were detected in the sera of 73 out of 138 patients (53%) referred to us because of Raynaud's phenomenon. When ANA were found, systemic manifestations were likely to be present. The use of human fibroblast monolayers as a nuclear substrate allowed differentiation of several fluorescence patterns, including the discrete speckled variety produced by anticentromere antibodies. These antibodies were detected in the sera of 7 out of 10 patients with CRST syndrome (70%), in 7 out of 40 patients with scleroderma (18%), all without kidney-involvement, in one patient with Sjögren's syndrome and severe Raynaud's phenomenon, and in 7 patients with Raynaud's phenomenon associated with a few symptoms of a connective tissue disease (especially scleroderma). ANA testing on tissue culture monolayers in Raynaud's phenomenon appears to be of value in predicting systemic disease manifestations and the presence or possible future development of distinct clinical patterns, especially the CRST syndrome. Images

Kallenberg, C G; Pastoor, G W; Wouda, A A; The, T H

1982-01-01

28

Anti-Nuclear Antibodies in Patients with Polycystic Ovary Syndrome before and after Laparoscopic Electrocauterization  

PubMed Central

Polycystic ovary syndrome (PCOS) has been suggested to be linked with autoimmune processes. Laparoscopic ovarian electrocauterization has the potency to stimulate more autoimmune reactions in PCOS patients. In the present study, we considered anti-nuclear antibodies (ANAs) as the hallmark of autoimmune reactions, and investigated the serum level of these antibodies in 35 patients with PCOS (21-38 years old) pre and one-month after electrocauterization, and in 35 fertile healthy women (25-35 years old) as the control group. Serum levels of ANAs, as well as ANA subtyping, were investigated using the Enzyme-Linked Immunosorbent Assay (ELISA). While 3 out of the 35 patients (8.6%) were positive for ANAs before electrocauterization, none of the controls was positive. The number of ANA-positive cases increased following electrocauterization (3 out of 35 [8.6%] before vs. 10 out of 35 [28.6%] after the procedure). The main ANA subtype in the positive samples was SS-A. The higher ANA level among the PCOS patients suggests association of the disease with autoimmune reactions. Laparoscopic ovarian electrocauterization seems to increase the number of positive-ANA patients.

Samsami Dehaghani, Alamtaj; Karimaghaei, Nazanin; Parsanezhad, Mohammad Ebrahim; Malekzadeh, Mahyar; Mehrazmay, Mohammad; Erfani, Nasrollah

2013-01-01

29

Adherence of Blood Components to Artificial Kidney Membranes (Anti-Nuclear Antibodies in Chronic Dialysis and Renal Transplantations).  

National Technical Information Service (NTIS)

Free nuclei of damaged leukocytes adhere to hemodialysis coil membranes. Exposure to nuclear antigens during hemodialysis may lead to antinuclear antibody formation. The authors has measured serum for antibodies to extractable nuclear antigens (ENA) and t...

K. D. Nolph G. C. Sharp

1974-01-01

30

Cold agglutinin-induced haemolysis in association with antinuclear antibody-negative SLE.  

PubMed

Systemic lupus erythematosus (SLE) is a chronic relapsing autoimmune disease associated with several autoantibodies targeted to nuclear and cytoplasmic antigens. Serum antinuclear antibody (ANA) is considered an important diagnostic marker of SLE. However, 2-3% of patients with typical clinical picture of SLE may have persistently negative ANA tests. Autoimmune haemolytic anaemia (AIHA) in SLE is usually mediated by warm IgG anti-erythrocyte antibodies. Our report describes a female patient who presented with clinical manifestations of SLE including photosensitivity, joint pains and AIHA. Further workup revealed high cold IgM agglutinin titres. A comprehensive workup for infectious aetiologies was negative. Autoimmune studies revealed negative ANA, but positive anti-double-stranded DNA and antiphospholipid antibodies. Lymphoproliferative disorder was excluded by imaging studies. Initial treatment with steroids proved of little benefit; however, rituximab resulted in significant clinical improvement. To the best of our knowledge, this is perhaps the first report of ANA-negative SLE presenting with cold AIHA. PMID:23761498

Chaubey, Vinod K; Chhabra, Lovely

2013-01-01

31

Comparison of indirect immunofluorescence and multiplex antinuclear antibody screening in systemic sclerosis  

Microsoft Academic Search

Indirect immunofluorescence antinuclear antibodies (IIF-ANA) are detected in approximately 90% of scleroderma patients, and\\u000a the staining pattern correlates with scleroderma-specific antibody subsets. Solid-phase ANA assays that are dependent on multiplex\\u000a bead technology (MULTIPLEX-ANA) are replacing immunofluorescence in many commercial labs; however, performance of these assays\\u000a has not been compared to IIF-ANA in scleroderma. The purpose of this study was to

Victoria K. Shanmugam; Donna R. Swistowski; Nicole Saddic; Hong Wang; Virginia D. Steen

32

A Comparison of Anti-Nuclear Antibody Quantification Using Automated Enzyme Immunoassays and Immunofluorescence Assays  

PubMed Central

Anti-nuclear antibodies (ANA) have traditionally been evaluated using indirect fluorescence assays (IFA) with HEp-2 cells. Quantitative immunoassays (EIA) have replaced the use of HEp-2 cells in some laboratories. Here, we evaluated ANA in 400 consecutive and unselected routinely referred patients using IFA and automated EIA techniques. The IFA results generated by two independent laboratories were compared with the EIA results from antibodies against double-stranded DNA (dsDNA), from ANA screening, and from tests of the seven included subantigens. The final IFA and EIA results for 386 unique patients were compared. The majority of the results were the same between the two methods (n = 325, 84%); however, 8% (n = 30) yielded equivocal results (equivocal-negative and equivocal-positive) and 8% (n = 31) yielded divergent results (positive-negative). The results showed fairly good agreement, with Cohen's kappa value of 0.30 (95% confidence interval (CI) = 0.14–0.46), which decreased to 0.23 (95% CI = 0.06–0.40) when the results for dsDNA were omitted. The EIA method was less reliable for assessing nuclear and speckled reactivity patterns, whereas the IFA method presented difficulties detecting dsDNA and Ro activity. The automated EIA method was performed in a similar way to the conventional IFA method using HEp-2 cells; thus, automated EIA may be used as a screening test.

Baronaite, Renata; Engelhart, Merete; M?rk Hansen, Troels; Thamsborg, Gorm; Slott Jensen, Hanne; Stender, Steen; Szecsi, Pal Bela

2014-01-01

33

Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evaluating Musculoskeletal Complaints in Children. Clinician Research Summary.  

National Technical Information Service (NTIS)

In response to a request from the public, a systematic review assessed the test performances of antinuclear antibody (ANA), rheumatoid factor (RF), and cyclic-citrullinated peptide (CCP) for pediatric systemic lupus erythematosus (pSLE) and juvenile idiop...

2012-01-01

34

The incidence of antinuclear antibodies (ANA) detected by indirect immunofluorescence assay (IFA) method.  

PubMed

Human anti-nuclear antibodies (ANA) in Systemic Lupus Erythematosus (SLE) react specificaly with DNA, RNA, several proteins and ribonucleoproteins. Systemic Lupus Erythematosus is the classic type of polysystemic autoimmune disease. The high frequency of ANA is determined in these patients. Actually, all SLE patients are ANA positive. ANA testing by IFA (Indirect Immunofluorescence Assay) is an excellent screening tool for SLE cases, but it is not so highly specific test. Patients with connective tissue diseases, such as rheumatoid arthritis, scleroderma and dermatomyositis are also frequently positive. Results of IFA ANA have relative low specific degree, and for this reason the titration of these specimens to the end point is usually recommended. Indirect immunoflourescence is reference method for ANA testing. Common substrates are thin sections of rodent organs or various types of cell lines. The cell line substrates are preferable to organ sections, because these rapidly dividing cells have higher level for detection of certain clinically relevant antigens such as (e.g., centromere, SSA (Ro) and Scl-70). In this paper we present the results evaluation of ANA incidence, detected by IFA in serum specimens of corresponding clinical patients, during 2005 and 2006. PMID:17582968

Karamehic, Jasenko; Subasic, Djemo; Gavrankapetanovic, Faris; Zecevic, Lamija; Eminovic, Izet; Memic, Senaid; Seric, Natasa; Drace, Zahida

2007-01-01

35

Detection and identification of antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing  

PubMed Central

OBJECTIVE—To provide data on (a) the probability of detecting antinuclear antibodies (ANA) in a large and consecutive cohort of serum samples referred for ANA testing and (b) the probability of detecting more specific antinuclear reactivities (anti-DNA and anti-extractable nuclear antigens (anti-ENA)) in serum samples with a positive screening test (indirect immunofluorescence on HEp-2 cells).?METHODS—Serum samples from 10 550 consecutive patients sent to the laboratory for ANA detection were analysed. In ANA positive serum samples (23.5% of referred serum samples), ANA were identified by indirect immunofluorescence on Crithidia, by immunodiffusion, and by line immunoassay. Because anti-SSA antibodies were the most frequently identified ANA, sensitively detected by line immunoassay, additional immunoassays were developed to confirm the specificity of the line immunoassay result.?RESULTS—At least one fine reactivity could be identified in 21.1% of ANA positive serum samples: anti-dsDNA in 3.2%; anti-ENA (anti-SSA 10.5%, anti-SSB 6.7%, anti-RNP 2.7%, anti-Sm 1.8%, anti-Scl70 1.2%, anti-Jo-1 0.2%) in 15.8%, rRNP and anti-Cenp-B in respectively 0.5% and 4.0%. Multiple reactivities were found in 7.9%. For anti-ENA antibodies, line immunoassay was more sensitive than immunodiffusion (15.4% v 7.7%; p<0.0001). The sensitive detection of anti-SSA antibodies by line immunoassay was confirmed by additional assays.?CONCLUSIONS—The data from this analysis are useful in estimating the probabilities of detecting specific ANA. Line immunoassay was shown to be a sensitive test for the detection of anti-ENA antibodies.??

Peene, I; Meheus, L; Veys, E; De Keyser, F

2001-01-01

36

Determination of Anti-nuclear Antibody Pattern Distribution and Clinical Relationship.  

PubMed

Background and Objectives: Autoantibodies are immunglobulins occurred directly against autoantigens that are known as endogen antigens. Autoimmune disease is an occasion that the body begins a fight against its own cells and tissues. The antibodies that are created by the body against its own cell nuclei are called as anti-nuclear antibodies (ANA), and one of the methods used for detection and pattern of ANA is indirect immunofluorescence test (IIF). In the present study, it was aimed to determine the rate of ANA positivity and patterns of the positive specimens, and to investigate the relationship between ANA positivity and diseases in patients. Methods: ANA test results of a total of 3127 patients admitted during March 2010 to December 2012 were evaluated retrospectively. ANA test (HEp 20-10, EUROIMMUN, Germany) was used in dilution of 1:100 in IIF test. Results: A total of 494 (15.8%) resulted as ANA positive. ANA positivity rate was significantly higher in female patients than the male ones (p<0.001). The most frequent ANA patterns were coarse speckled pattern (154 patients, 31.2%), nucleolar pattern (89 patients, 18.0%), fine speckled pattern (57 patients, 11.5%), and speckled pattern (48 patients, 9.7%). ANA positivity was most commonly determined in rheumatoid arthritis (RA) (42 patients, 8.5%), systemic lupus erythematosus (SLE) (29 patients, 5.9%), and rheumatoid vasculitis (RV) (28 patients, 5.7%). The most frequent symptoms or findings were joint pain (127 patients, 26.0%) and anemia (28 patients, 5.7%). ANA positivity rates were found to be significantly higher in patients with RA (p<0.001), with SLE (p<0.001), and with Raynaud phenomenon (p=0.001) in comparison to the controls. Amongst the most frequent diseases evaluated, no significant differences were found between the control groups and the groups of RV (p=0.089), multiple sclerosis (p=0.374), and Sjögren syndrome (p=0.311) in terms of ANA positivity rates. Conclusions: The present study is the first study reporting the positivity rate and distribution of ANA in Bolu located in northwestern Turkey. Information about the pattern types and the distribution of the patterns according to the diseases and symptoms contribute in diagnosis of autoimmune diseases. It is observed that clinical diagnosis has been supported significantly by ANA test according to data of our study. PMID:24772147

Mengeloglu, Zafer; Tas, Tekin; Kocoglu, Esra; Aktas, Gülali; Karabörk, Seyda

2014-03-01

37

Determination of Anti-nuclear Antibody Pattern Distribution and Clinical Relationship  

PubMed Central

Background and Objectives: Autoantibodies are immunglobulins occurred directly against autoantigens that are known as endogen antigens. Autoimmune disease is an occasion that the body begins a fight against its own cells and tissues. The antibodies that are created by the body against its own cell nuclei are called as anti-nuclear antibodies (ANA), and one of the methods used for detection and pattern of ANA is indirect immunofluorescence test (IIF). In the present study, it was aimed to determine the rate of ANA positivity and patterns of the positive specimens, and to investigate the relationship between ANA positivity and diseases in patients. Methods: ANA test results of a total of 3127 patients admitted during March 2010 to December 2012 were evaluated retrospectively. ANA test (HEp 20-10, EUROIMMUN, Germany) was used in dilution of 1:100 in IIF test. Results: A total of 494 (15.8%) resulted as ANA positive. ANA positivity rate was significantly higher in female patients than the male ones (p<0.001). The most frequent ANA patterns were coarse speckled pattern (154 patients, 31.2%), nucleolar pattern (89 patients, 18.0%), fine speckled pattern (57 patients, 11.5%), and speckled pattern (48 patients, 9.7%). ANA positivity was most commonly determined in rheumatoid arthritis (RA) (42 patients, 8.5%), systemic lupus erythematosus (SLE) (29 patients, 5.9%), and rheumatoid vasculitis (RV) (28 patients, 5.7%). The most frequent symptoms or findings were joint pain (127 patients, 26.0%) and anemia (28 patients, 5.7%). ANA positivity rates were found to be significantly higher in patients with RA (p<0.001), with SLE (p<0.001), and with Raynaud phenomenon (p=0.001) in comparison to the controls. Amongst the most frequent diseases evaluated, no significant differences were found between the control groups and the groups of RV (p=0.089), multiple sclerosis (p=0.374), and Sjögren syndrome (p=0.311) in terms of ANA positivity rates. Conclusions: The present study is the first study reporting the positivity rate and distribution of ANA in Bolu located in northwestern Turkey. Information about the pattern types and the distribution of the patterns according to the diseases and symptoms contribute in diagnosis of autoimmune diseases. It is observed that clinical diagnosis has been supported significantly by ANA test according to data of our study.

Mengeloglu, Zafer; Tas, Tekin; Kocoglu, Esra; Aktas, Gulali; Karabork, Seyda

2014-01-01

38

Higher Serum Levels of Rheumatoid Factor and Anti-Nuclear Antibodies in Helicobacter Pylori-Infected Peptic Ulcer Patients  

PubMed Central

Objectives H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. Methods A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects (as a control group) were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. Results The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group (p<0.05). Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men (p<0.05). Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. Conclusion The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection.

Jafarzadeh, Abdollah; Nemati, Maryam; Rezayati, Mohammad Taghi; Nabizadeh, Mansooreh; Ebrahimi, Medhi

2013-01-01

39

Comparison of indirect immunofluorescence and multiplex antinuclear antibody screening in systemic sclerosis.  

PubMed

Indirect immunofluorescence antinuclear antibodies (IIF-ANA) are detected in approximately 90% of scleroderma patients, and the staining pattern correlates with scleroderma-specific antibody subsets. Solid-phase ANA assays that are dependent on multiplex bead technology (MULTIPLEX-ANA) are replacing immunofluorescence in many commercial labs; however, performance of these assays has not been compared to IIF-ANA in scleroderma. The purpose of this study was to evaluate whether a proportion of scleroderma patients have negative testing on MULTIPLEX-ANA assays and demonstrate whether negative MULTIPLEX-ANA is associated with particular scleroderma-specific autoantibodies. A retrospective chart review was completed on all 238 scleroderma patients evaluated in the Georgetown scleroderma clinic between June 1, 2008 and May 31, 2009. Autoantibody results, demographics, and scleroderma features were collected. Data were analyzed using unpaired t test and Mann-Whitney U test for continuous variables, and Fisher's exact test for dichotomous variables. Simple kappa coefficient was used to measure the level of agreement between MULTIPLEX-ANA and IIF-ANA results. Two-tailed p values <0.05 were considered significant. MULTIPLEX-ANA testing was available in 57 patients and only 29 (51%) tested positive. In contrast, IIF-ANA was positive in 91% of these patients. Using simple kappa coefficient, there was a good agreement between the MULTIPLEX-ANA, and presence of Scl70, RNP, and centromere antibodies (0.76; 95% CI 0.59, 0.92), but there was no agreement between MULTIPLEX-ANA and presence of other IIF-ANA patterns including nucleolar ANA (-0.40; 95% CI -0.64, -0.16). Because RNA polymerase III and nucleolar antibodies are seen in 43% of the entire scleroderma population, we are concerned that these false-negative tests could result in delays in referral and diagnosis. Until the MULTIPLEX-ANA assays can be modified to include the antigens for RNA polymerase III and the nucleolar ANA subsets, IIF-ANA remains the recommended screening test for ANA in suspected scleroderma. PMID:21614475

Shanmugam, Victoria K; Swistowski, Donna R; Saddic, Nicole; Wang, Hong; Steen, Virginia D

2011-10-01

40

Immunoregulation and anti-nuclear antibodies in mercury-induced glomerulopathy in the rat.  

PubMed Central

The pathogenesis of drug-induced autoimmune antibodies is in most cases uncertain. The recent demonstration of T cell aberrations in human and experimental drug-induced autoimmune disease suggests that immunodysregulation might form the basis of an uncontrolled B cell autoreactivity leading to autoantibody production. In the present study, lymphocytic stimulation by phytohemagglutinin (PHA) and concanavalin A-activated suppressor cell activity was measured in an experimental model of mercury-induced immune complex glomerulopathy associated with anti-nuclear antibodies and vasculitis in PVG/c rats. Both general T cell reactivity to PHA and concanavalin A-activated suppressor function as measured by a syngeneic target cell assay were found to be significantly decreased in mercury-diseased rats as compared with saline-injected control rats. Furthermore, the effect of neonatal and adult thymectomy on the course of the mercury-induced disease was studied. Anti-nuclear antibody activity and glomerular immune aggregate formation were found to be accelerated considerably by neonatal thymectomy, whereas thymectomy at adult age had no significant effect on the interval between the start of mercury administration and the appearance of serological and renal abnormalities. From the results it is concluded that mercury affects both effector and regulatory T cell functions and that immunodysregulation seems to be of pathogenetic significance in this model of drug-induced disease.

Weening, J J; Hoedemaeker, P J; Bakker, W W

1981-01-01

41

Immune-Mediated Fever in the Dog. Occurrence of Antinuclear Antibodies, Rheumatoid Factor, Tumor Necrosis Factor and Interleukin-6 in Serum  

PubMed Central

Contents of antinuclear antibodies (ANA), rheumatoid factor (RF), tumor necrosis factor (TNF-?) and interleukin-6 (IL-6) were measured in serum from 20 dogs with immune-mediated fever. Seven out of 20 patients were ANA positive, 1 out of 20 was positive to antibodies against extractable nuclear antigens (ENA), 1 out of 20 was positive to antibodies against deoxynucleoproteins (DNP), 2 out of 13 were RF positive and none out of 20 patients had antibodies against native DNA in the serum. TNF-? was not detected in any serum of 15 dogs with immune-mediated fever, while 10 out of 13 presented with elevated IL-6. The results varied between patients, but the IL-6 level was high in most of them. This indicate a role for IL-6 in the pathogenesis of immune-mediated fever in most cases.

Bohnhorst, ?vreb?; Hanssen, I; Moen, Torolf

2002-01-01

42

IgG rheumatoid factors and anti-nuclear antibodies in rheumatoid vasculitis.  

PubMed Central

We studied the distribution and characteristics of circulating rheumatoid factors (RF) and anti-nuclear antibodies (ANA) in 30 rheumatoid arthritis (RA) patients who had polyarthritis alone (group I), 28 RA patients with polyarthritis and extra-articular disease (group II), 28 RA patients with systemic vasculitis (group III) and 60 healthy matched controls. IgG RF occurred more frequently and in higher serum titres in group III (100%) than RA patients in group I (40%), or in group II (18%) or in normal controls (5.8%). The serum titre of IgM RF was higher in vasculitis patients than in other RA patients. ANA were found in 74% of all RA patients and although the frequency did not differ in the three patient groups, the serum titre was significantly higher in the vasculitis group. Antibodies to extractable nuclear antigen were found only in group III (18.7%). Antibodies to histones were also more prevalent in group III than in the other RA groups. The serological abnormalities in rheumatoid vasculitis differed quantitatively as well as qualitatively from other RA patients.

Quismorio, F P; Beardmore, T; Kaufman, R L; Mongan, E S

1983-01-01

43

Mercury induced antinuclear antibodies in mice: characterization and correlation with renal immune complex deposits.  

PubMed Central

Female SJL and Balb/c mice were given subcutaneous injections of 1.6 mg HgCl2/kg body weight every third day for 2, 4, 8, or 12 weeks. Indirect immunofluorescence using HEp-2 cells as substrate showed that SJL mice developed antinuclear antibodies (ANA) with a predominantly nucleolar and a weaker, homogeneous nuclear pattern after 4 weeks treatment. The nucleolar antigen was sensitive to treatment with trypsin and RNAse, but the antibody was not absorbed by calf liver RNA. The antigen responsible for the homogeneous nuclear pattern was sensitive to treatment with trypsin, DNAse, and acid solution, but reconstitution with histones on acid treated substrate did not restore the fluorescence. The corresponding antibody was not absorbed by double-stranded or single-stranded DNA, and the Crithidia luciliae assay was negative. This suggests that the antigen responsible for the homogeneous ANA pattern is a non-histone chromatin protein. No autoantibodies were found in Balb/c mice. Electron dense immune deposits containing IgG and C3 in a mesangial-vascular pattern developed after 4 weeks mercury treatment in SJL and Balb/c mice. Acid eluate from kidneys of SJL mice with immune deposits contained tissue-bound ANA with a strictly anti-nucleolar pattern, showing that such antibodies make up part of the renal immune deposits. No autoantibodies were found in the eluate from Balb/c mice. The findings demonstrate that mercury induces a polyclonal autoantibody response in SJL mice, and suggests a restricted antibody response with unknown specificity in Balb/c mice, in both cases leading to immune complex deposits in the kidneys. Images Fig. 3

Hultman, P; Enestrom, S

1988-01-01

44

Development of the Antinuclear and Anticytoplasmic Antibody Consensus Panel by the Association of Medical Laboratory Immunologists  

PubMed Central

The Association of Medical Laboratory Immunologists (AMLI) have developed a panel of antinuclear and anticytoplasmic antibody consensus sera that can be useful for enzyme immunoassay (EIA), Ouchterlony, and immunofluorescence assay methods. It was developed to assist in the evaluation of newly available EIA methods for the detection of autoantibodies. The panel of sera was evaluated in several clinical laboratories and a large number of laboratories owned by manufacturers of clinical autoantibody testing kits. The majority of sera performed well for the EIAs in both the clinical laboratories and the manufacturers' laboratories, but some samples had discrepant results. A major source of discrepancy is the current inability of the EIA results to be directly compared in a quantitative way as no standardization exists. The evaluation demonstrated lower sensitivity of detection by the Ouchterlony method. The limited evaluation of the sera with immunoblotting and Western blotting did not show good agreement with other methods. Further work must be done to standardize blotting methods prior to their use in routine clinical testing. The sera are now available to vendors and clinical laboratories for use in the detection of SS-A, SS-B, Sm, U1-RNP, Scl-70, Jo-1, double-stranded DNA, and centromere antibodies. The availability of the consensus sera will help evaluate and improve the EIA methods currently being used.

James, Karen; Carpenter, A. Betts; Cook, Linda; Marchand, Richard; Nakamura, Robert M.

2000-01-01

45

An automatic segmentation and classification framework for anti-nuclear antibody images  

PubMed Central

Autoimmune disease is a disorder of immune system due to the over-reaction of lymphocytes against one's own body tissues. Anti-Nuclear Antibody (ANA) is an autoantibody produced by the immune system directed against the self body tissues or cells, which plays an important role in the diagnosis of autoimmune diseases. Indirect ImmunoFluorescence (IIF) method with HEp-2 cells provides the major screening method to detect ANA for the diagnosis of autoimmune diseases. Fluorescence patterns at present are usually examined laboriously by experienced physicians through manually inspecting the slides with the help of a microscope, which usually suffers from inter-observer variability that limits its reproducibility. Previous researches only provided simple segmentation methods and criterions for cell segmentation and recognition, but a fully automatic framework for the segmentation and recognition of HEp-2 cells had never been reported before. This study proposes a method based on the watershed algorithm to automatically detect the HEp-2 cells with different patterns. The experimental results show that the segmentation performance of the proposed method is satisfactory when evaluated with percent volume overlap (PVO: 89%). The classification performance using a SVM classifier designed based on the features calculated from the segmented cells achieves an average accuracy of 96.90%, which outperforms other methods presented in previous studies. The proposed method can be used to develop a computer-aided system to assist the physicians in the diagnosis of auto-immune diseases.

2013-01-01

46

Meta-Analysis: Diagnostic Accuracy of Antinuclear Antibodies, Smooth Muscle Antibodies and Antibodies to a Soluble Liver Antigen/Liver Pancreas in Autoimmune Hepatitis  

PubMed Central

Background Antinuclear antibodies (ANA), smooth muscle antibodies (SMA) and antibodies to a soluble liver antigen/liver pancreas (anti-SLA/LP) are useful markers that can help clinicians to diagnose and classify autoimmune hepatitis (AIH). Objectives To determine whether ANA, SMA and anti-SLA/LP help to accurately diagnose patients with AIH. Search strategy The PubMed, CNKI, WANFANG, and SinoMed databases were accessed to retrieve studies published in English and Chinese. Studies published up to October 2013 were reviewed. Selection criteria Studies on the diagnostic value of ANA, SMA or anti-SLA/LP in the diagnosis of known or suspected AIH were included. Data collection and analysis Two authors evaluated studies independently and rated their methodological quality using quality assessment of diagnostic accuracy studies (QUADAS) tools; relevant data were abstracted. The random-effects method was used to summarize sensitivities, specificities, positive and negative likelihood ratios, and diagnostic odds ratios (DORs) from all 29 studies. Results The pooled sensitivity, specificity, positive and negative likelihood ratios, and DOR for ANA were 0.650 (95% confidence interval [CI], 0.619 to 0.680), 0.751 (95%CI, 0.737 to 0.764), 3.030 (95%CI, 2.349 to 3.910), 0.464 (95%CI, 0.356 to 0.604), and 7.380 (95%CI, 4.344 to 12.539), respectively. For SMA, the values were 0.593 (95%CI, 0.564 to 0.621), 0.926 (95%CI, 0.917 to 0.934), 11.740 (95%CI, 7.379 to 18.678), 0.449 (95%CI, 0.367 to 0.549), and 31.553 (95%CI, 17.147 to 58.060), respectively. Finally, for anti-SLA/LP, the values were 0.194 (95%CI, 0.168 to 0.222), 0.989 (95%CI, 0.985 to 0.993), 11.089 (95%CI, 7.601 to 16.177), 0.839 (95%CI, 0.777 to 0.905), and 16.867 (95%CI, 10.956 to 25.967), respectively. Authors’ conclusions ANA provided moderate sensitivity and specificity, while SMA gave moderate sensitivity and high specificity, and anti-SLA/LP exhibited low sensitivity and high specificity. All three antibodies were limited by their unsatisfactory sensitivities and lack of consistency.

Chen, Juan; Chen, Wei-Xian

2014-01-01

47

Evaluation of anti-nuclear antibodies and kidney pathology in Lewis rats following exposure to Libby amphibole asbestos.  

PubMed

The prevalence of anti-nuclear antibodies (ANA) and self-reported systemic autoimmune diseases were increased in residents of Libby, MT, as was the incidence of ANA in Lewis rats exposed to Libby amphibole (LA) asbestos. However, rats induced to develop rheumatoid arthritis (RA) did not develop autoantibodies associated with RA, nor was RA exacerbated by LA exposure, suggesting that increased ANA expression might be related to some other autoimmune process. Libby residents self-reported increased numbers of physician-diagnosed cases of systemic lupus erythematosus (SLE). Thus, the goal of this study was to determine if the increased incidence of ANA in Lewis rats exposed to LA is related to the development of SLE-like disease. Female Lewis rats were intratracheally instilled bi-weekly for 13 weeks with total doses of 0.15, 0.5, 1.5, or 5.0?mg of LA or 0.5 or 1.5?mg of a positive control fiber, amosite. ANA incidence was significantly increased in all asbestos dose groups, although no dose response was observed. The occurrence of proteinuria was increased in LA 0.5, LA 5.0, and amosite 0.5 dose groups; however, the microscopic appearance of the kidneys was normal, no binding of autoimmune complexes to glomerular surfaces was observed, and antibodies to double-stranded DNA were not elevated. Therefore, an increased prevalence of ANA in rats exposed to asbestos does not appear to correlate with disease markers typically observed in SLE. Analysis of ANA specificity for extractable nuclear antigens (ENA) determined that 98% of ENA(+) samples were specific for the Jo-1 antigen. Autoantibodies to Jo-1 have been reported in patients with interstitial lung disease, suggesting that autoantibodies to Jo-1 may be a biomarker for asbestos-related pulmonary disease. PMID:23256773

Salazar, Keith D; Copeland, Carey B; Wood, Charles E; Schmid, Judith E; Luebke, Robert W

2013-01-01

48

Associations between antinuclear antibody staining patterns and clinical features of systemic lupus erythematosus: analysis of a regional Swedish register  

PubMed Central

Objective Antinuclear antibody (ANA) analysis by immunofluorescence (IF) microscopy remains a diagnostic hallmark of systemic lupus erythematosus (SLE). The clinical relevance of ANA fine-specificities in SLE has been addressed repeatedly, whereas studies on IF-ANA staining patterns in relation to disease manifestations are very scarce. This study was performed to elucidate whether different staining patterns associate with distinct SLE phenotypes. Design Observational cohort study. Setting One university hospital rheumatology unit in Sweden. Participants The study population consisted of 222 cases (89% women; 93% Caucasians), where of 178 met ?4/11 of the 1982 American College of Rheumatology (ACR-82) criteria. The remaining 20% had an SLE diagnosis based on positive IF-ANA (HEp-2 cells) and ?2 typical organ manifestations at the time of diagnosis (Fries’ criteria). Outcome measures The IF-ANA staining patterns homogenous (H-ANA), speckled (S-ANA), combined homogenous and speckled (HS-ANA), centromeric (C-ANA), nucleolar (N-ANA)±other patterns and other nuclear patterns (oANA) were related to disease manifestations and laboratory measures. Antigen-specificities were also considered regarding double-stranded DNA (Crithidia luciliae) and the following extractable nuclear antigens: Ro/SSA, La/SSB, Smith antigen (Sm), small nuclear RNP (snRNP), Scl-70 and Jo-1 (immunodiffusion and/or line-blot technique). Results 54% of the patients with SLE displayed H-ANA, 22% S-ANA, 11% HS-ANA, 9% N-ANA, 1% C-ANA, 2% oANA and 1% were never IF-ANA positive. Staining patterns among patients meeting Fries’ criteria alone did not differ from those fulfilling ACR-82. H-ANA was significantly associated with the 10th criterion according to ACR-82 (‘immunological disorder’). S-ANA was inversely associated with arthritis, ‘immunological disorder’ and signs of organ damage. Conclusions H-ANA is the dominant IF-ANA pattern among Swedish patients with SLE, and was found to associate with ‘immunological disorder’ according to ACR-82. The second most common pattern, S-ANA, associated negatively with arthritis and organ damage.

Frodlund, Martina; Dahlstrom, Orjan; Kastbom, Alf; Skogh, Thomas; Sjowall, Christopher

2013-01-01

49

Induction of Antinuclear Antibodies by De Novo Autoimmune Hepatitis Regulates Alloimmune Responses in Rat Liver Transplantation  

PubMed Central

Concanavalin A (Con A) is a lectin originating from the jack-bean and well known for its ability to stimulate T cells and induce autoimmune hepatitis. We previously demonstrated the induction of immunosuppressive antinuclear autoantibody in the course of Con A-induced transient autoimmune hepatitis. This study aimed to clarify the effects of Con A-induced hepatitis on liver allograft rejection and acceptance. In this study, we observed the unique phenomenon that the induction of transient de novo autoimmune hepatitis by Con A injection paradoxically overcomes the rejection without any immunosuppressive drug and exhibits significantly prolonged survival after orthotopic liver transplantation (OLT). Significantly increased titers of anti-nuclear Abs against histone H1 and high-mobility group box 1 (HMGB1) and reduced donor specific alloantibody response were observed in Con A-injected recipients. Induction of Foxp3 and IL-10 in OLT livers of Con A-injected recipients suggested the involvement of regulatory T cells in this unique phenomenon. Our present data suggest the significance of autoimmune responses against nuclear histone H1 and HMGB1 for competing allogeneic immune responses, resulting in the acceptance of liver allografts in experimental liver transplantation.

Nakano, Toshiaki; Goto, Shigeru; Lai, Chia-Yun; Hsu, Li-Wen; Tseng, Hui-Peng; Chen, Kuang-Den; Wang, Chih-Chi; Cheng, Yu-Fan; Chen, Chao-Long

2013-01-01

50

Evaluation of fluorescent antinuclear antibody assays, Crithidia luciliae substrate, and single-stranded DNA-binding capacity in diagnosis of four rheumatic diseases.  

PubMed Central

Sera from groups of patient with systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, and progressive systemic sclerosis and normal controls were compared, using different antinuclear antibody assays. Hep-II cells, used as a substrate for the detection of antinuclear antibodies, appeared to be more sensitive than rat liver substrate. In addition, the fluorescent patterns were easier to identify on Hep-II cells. All systemic lupus erythematosus sera with antibodies reactive with kinetoplasts of Crithidia luciliae had binding greater than 43% for single-stranded DNA. Based on the high sensitivity of the Hep-II substrate and the relative specificity of high (greater than 43%) binding for single stranded DNA by sera from patients with systemic lupus erythematosus, it appears that these two tests are most useful in differential diagnosis and for the detection of systemic lupus erythematosus.

Chiang, M; Chia, D; Barnett, E V

1982-01-01

51

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

SciTech Connect

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 -/-} 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.

Wang, Yuehai [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Huang, Ziyang, E-mail: huangziyang666@126.com [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Lu, Huixia [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Huili; Wang, Zhenhua [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Chen, Xiaoqing [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Ouyang, Qiufang [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Tang, Mengxiong; Hao, Panpan [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Ni, Jingqin [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Cardiovascular Department, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Xu, Dongming [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); Zhang, Mingxiang; Zhang, Qunye [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China)] [Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Chinese Ministry of Health, Shandong University, Qilu Hospital, Jinan, Shandong 250012 (China); Lin, Ling [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China)] [Department of Rheumatism and Immunology, Second Clinical Medical College, Fujian Medical University, Quanzhou, Fujian 362000 (China); and others

2012-07-13

52

Role of Nucleic Acid-Sensing TLRs in Diverse Autoantibody Specificities and Anti-nuclear Antibody-Producing B Cells  

PubMed Central

Nucleic acid (NA)–sensing TLRs (NA-TLRs) promote the induction of anti-nuclear Abs in systemic lupus erythematosus. However, the extent to which other nonnuclear pathogenic autoantibody specificities that occur in lupus and independently in other autoimmune diseases depend on NA-TLRs, and which immune cells require NA-TLRs in systemic autoimmunity, remains to be determined. Using Unc93b13d lupus-prone mice that lack NA-TLR signaling, we found that all pathogenic nonnuclear auto-antibody specificities examined, even anti-RBC, required NA-TLRs. Furthermore, we document that NA-TLRs in B cells were required for the development of antichromatin and rheumatoid factor. These findings support a unifying NA-TLR–mediated mechanism of autoantibody production that has both pathophysiological and therapeutic implications for systemic lupus erythematosus and several other humoral-mediated autoimmune diseases. In particular, our findings suggest that targeting of NA-TLR signaling in B cells alone would be sufficient to specifically block production of a broad diversity of autoantibodies.

Koh, Yi Ting; Scatizzi, John C.; Gahan, Jennifer D.; Lawson, Brian R.; Baccala, Roberto; Pollard, K. Michael; Beutler, Bruce A.; Theofilopoulos, Argyrios N.; Kono, Dwight H.

2013-01-01

53

Current Concepts and Future Directions for the Assessment of Autoantibodies to Cellular Antigens Referred to as Anti-Nuclear Antibodies  

PubMed Central

The detection of autoantibodies that target intracellular antigens, commonly termed anti-nuclear antibodies (ANA), is a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). Different methods are available for detection of ANA and all bearing their own advantages and limitations. Most laboratories use the indirect immunofluorescence (IIF) assay based on HEp-2 cell substrates. Due to the subjectivity of this diagnostic platform, automated digital reading systems have been developed during the last decade. In addition, solid phase immunoassays using well characterized antigens have gained widespread adoption in high throughput laboratories due to their ease of use and open automation. Despite all the advances in the field of ANA detection and its contribution to the diagnosis of SARD, significant challenges persist. This review provides a comprehensive overview of the current status on ANA testing including automated IIF reading systems and solid phase assays and suggests an approach to interpretation of results and discusses meeting the problems of assay standardization and other persistent challenges.

Mahler, Michael; Meroni, Pier-Luigi; Bossuyt, Xavier; Fritzler, Marvin J.

2014-01-01

54

Anti-Nuclear Antibody Production and Autoimmunity in Transgenic Mice that Over-Express the Transcription Factor Bright  

PubMed Central

The B cell-restricted transcription factor, Bright, up-regulates immunoglobulin heavy chain transcription three- to seven-fold in activated B cells in vitro. Bright function is dependent upon both active Bruton’s tyrosine kinase and its substrate, the transcription factor, TFII-I. In mouse and human B lymphocytes, Bright transcription is down regulated in mature B cells, and its expression is tightly regulated during B cell differentiation. To determine how Bright expression affects B cell development, transgenic mice were generated that express Bright constitutively in all B lineage cells. These mice exhibited increases in total B220+ B lymphocyte lineage cells in the bone marrow, but the relative percentages of the individual subpopulations were not altered. Splenic immature transitional B cells were significantly expanded both in total cell numbers and as increased percentages of cells relative to other B cell subpopulations. Serum immunoglobulin levels, particularly IgG isotypes, were increased slightly in the Bright transgenic mice compared to littermate controls. However, immunization studies suggest that responses to all foreign antigens were not increased globally. Moreover, four week-old Bright transgenic mice produced anti-nuclear antibodies. Older animals developed antibody deposits in the kidney glomeruli, but did not succumb to further autoimmune sequelae. These data indicate that enhanced Bright expression results in failure to maintain B cell tolerance and suggest a previously unappreciated role for Bright regulation in immature B cells. Bright is the first B cell-restricted transcription factor demonstrated to induce autoimmunity. Therefore, the Bright transgenics provide a novel model system for future analyses of B cell autoreactivity.

Shankar, Malini; Nixon, Jamee C.; Maier, Shannon; Workman, Jennifer; Farris, A. Darise; Webb, Carol F.

2009-01-01

55

Relation between antinuclear antibodies and the autoimmune rheumatic diseases and disease type and activity in systemic lupus erythematosus using a variety of cultured cell lines.  

PubMed Central

Antinuclear activity was assessed in serum samples from a series of 40 patients with differing clinical subsets (including renal and neurological disease) of systemic lupus erythematosus (SLE) against a transformed keratinocyte line (SvK14)* and normal human keratinocytes. Paired serum samples were studied during disease activity and inactivity, and the effects of ultraviolet radiation on the availability of nuclear antigens in the cell substrates were assessed. Serum samples from 20 healthy controls and 40 disease controls, comprising 10 patients each with rheumatoid arthritis, Sjögren's syndrome, scleroderma, and myositis, were also studied. The keratinocytes all provided sensitive substrates for the detection of antinuclear antibodies (ANAs), and in normal keratinocytes treated with ultraviolet radiation nuclear antigens were exposed on the cell surface. There was no correlation between ANAs and disease activity or patterns so, apart from assisting diagnosis, the detection of ANAs is of little relevance to predicting disease activity. Images

Sequi, J; Leigh, I; Isenberg, D A

1991-01-01

56

Anti-nuclear antibody reactivity in lupus may be partly hardwired into the primary B cell repertoire  

PubMed Central

When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited 3 sequence motifs in their immunoglobulin heavy chains, including increased cationicity in CDR3 (“motif A”), reduced anionicity in CDR2 (“motif B”) and increased aspartate at H50 (“motif C”). The present study was designed to elucidate the extent to which these ANA-associated sequence motifs might be hard-wired into the primary B-cell repertoire in lupus. The immunoglobulin heavy chain sequence of total splenic B cells, follicular B-cells and marginal zone B-cells from B6.Sle1 congenic mice and C57BL/6 controls were amplified by single cell PCR and compared. Analysis of the primary immunoglobulin heavy chain repertoire indicated that the first 2 sequence motifs “A” and “B” were already encoded in the naïve repertoire of B6.Sle1z mice, whereas the third motif “C” was introduced in part by somatic mutation. Site-directed mutagenesis confirmed that non-anionic CDR2 and cationic CDR3 residues in the immunoglobulin heavy chain facilitated nuclear antigen binding in concert, whereas aspartate at H50 strongly vetoed DNA-binding, while preserving nucleosome reactivity. Hence, antinuclear antibodies appear to arise as a consequence of 2 distinct processes–genetically programmed selection of specific CDR charge motifs into the primary immunoglobulin repertoire, with secondary contribution from somatic mutation. Polymorphisms in the lupus susceptibility gene Ly108 that impair central B-cell tolerance may be mechanistically responsible for these early repertoire differences in lupus.

Chang, Sooghee; Yang, Liu; Moon, Young Mee; Cho, Young Gyu; Min, So Youn; Kim, Tae Joo; Kim, Young Joo; Patrick, Wilson; Kim, Ho-Youn; Mohan, Chandra

2009-01-01

57

Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure  

PubMed Central

Formation of pulmonary tertiary immune structures is a characteristic feature of advanced COPD. In the current study, we investigated the mechanisms of tertiary lymphoid tissue (TLT) formation in the lungs of cigarette smoke-exposed mice. We found that cigarette smoke exposure led to TLT formation that persisted following smoking cessation. TLTs consisted predominantly of IgM positive B cells, while plasma cells in close proximity to TLTs expressed IgM, IgG, and IgA. The presence of TLT formation was associated with anti-nuclear autoantibody (ANA) production that also persisted following smoking cessation. ANAs were observed in the lungs, but not the circulation of cigarette smoke-exposed mice. Similarly, we observed ANA in the sputum of COPD patients where levels correlated with disease severity and were refractory to steroid treatment. Both ANA production and TLT formation were dependent on interleukin-1 receptor 1 (IL-1R1) expression. Contrary to TLT and ANA, lung neutrophilia resolved following smoking cessation. These data suggest a differential regulation of innate and B cell-related immune inflammatory processes associated with cigarette smoke exposure. Moreover, our study further emphasizes the importance of interleukin-1 (IL-1) signaling pathways in cigarette smoke-related pulmonary pathogenesis.

2014-01-01

58

Persistence of pulmonary tertiary lymphoid tissues and anti-nuclear antibodies following cessation of cigarette smoke exposure.  

PubMed

Formation of pulmonary tertiary immune structures is a characteristic feature of advanced COPD. In the current study, we investigated the mechanisms of tertiary lymphoid tissue (TLT) formation in the lungs of cigarette smoke-exposed mice. We found that cigarette smoke exposure led to TLT formation that persisted following smoking cessation. TLTs consisted predominantly of IgM positive B cells, while plasma cells in close proximity to TLTs expressed IgM, IgG, and IgA. The presence of TLT formation was associated with anti-nuclear autoantibody (ANA) production that also persisted following smoking cessation. ANAs were observed in the lungs, but not the circulation of cigarette smoke-exposed mice. Similarly, we observed ANA in the sputum of COPD patients where levels correlated with disease severity and were refractory to steroid treatment. Both ANA production and TLT formation were dependent on interleukin-1 receptor 1 (IL-1R1) expression. Contrary to TLT and ANA, lung neutrophilia resolved following smoking cessation. These data suggest a differential regulation of innate and B cell-related immune inflammatory processes associated with cigarette smoke exposure. Moreover, our study further emphasizes the importance of interleukin-1 (IL-1) signaling pathways in cigarette smoke-related pulmonary pathogenesis. PMID:24754996

Morissette, Mathieu C; Jobse, Brian N; Thayaparan, Danya; Nikota, Jake K; Shen, Pamela; Labiris, Nancy Renée; Kolbeck, Roland; Nair, Parameswaran; Humbles, Alison A; Stämpfli, Martin R

2014-01-01

59

Automated indirect immunofluorescence microscopy enables the implementation of a quantitative internal quality control system for anti-nuclear antibody (ANA) analysis.  

PubMed

Abstract Background: Screening for anti-nuclear antibodies by indirect immunofluorescence (ANA-IIF) remains mandatory in the serological work-up of connective tissue diseases. Recently, automated approaches were introduced that may improve harmonization. Here, we investigated whether the introduction of automated ANA-IIF and more specifically the use of its quantitative measure, could improve ANA-IIF internal quality control (IQC) management. Methods: We retrospectively reviewed results of two cohorts of routine samples and parallel IQC data collected from January 2010 to February 2013 and from February to mid October 2013. For the first cohort, data were collected using conventional microscopy. The second cohort was analyzed by an automated ANA-IIF microscope (Zenit G sight, A. Menarini). Retrospectively, we evaluated the applicability of the probability index (PI) of control material measurements and patient results for IQC management based on Westgard multirules. This approach was also compared with monthly monitoring of the %ANA-IIF positive samples. Results: In our historical data set, we showed that monitoring of %ANA positives identified systematic errors that were not detected by monitoring control material results. Data resulting from automated microscopy showed that PI measurements on control material remained stable within the observed period and that Westgard multirules can be used for IQC follow-up. Parallel monitoring of the daily median patient PI and the monthly %ANA positives, showed that the daily median was a sensitive and fast tool for detecting systematic errors. Conclusions: The introduction of the automated ANA-IIF microscope could enable objective IQC procedures and should be considered an important step forward in ANA-IIF harmonization. PMID:24598837

Maenhout, Thomas M; Bonroy, Carolien; Verfaillie, Charlotte; Stove, Veronique; Devreese, Katrien

2014-07-01

60

ANA (Antinuclear Antibody Test)  

MedlinePLUS

... is to perform additional testing for the autoantibodies Smith and ds-DNA, which, if possitive, would confirm ... Rheumatoid Arthritis , Sjögren Syndrome , Scleroderma Elsewhere On The Web Lupus Foundation of America American College of Rheumatology: ...

61

Antinuclear antibody panel  

MedlinePLUS

... have signs of an autoimmune disorder, particularly systemic lupus erythematosus . This test may be done if you ... ANA does not confirm a diagnosis of systemic lupus erythematosis (SLE). However, a lack of ANA makes ...

62

Can Administration of Potentized Homeopathic Remedy, Arsenicum Album, Alter Antinuclear Antibody (ANA) Titer in People Living in High-Risk Arsenic Contaminated Areas? I. A Correlation with Certain Hematological Parameters  

Microsoft Academic Search

To examine whether elevated antinuclear antibody (ANA) titers reported in random human population of arsenic contaminated villages can be reverted to the normal range by administration of a potentized homeopathic drug, Arsenicum album, randomly selected volunteers in two arsenic contaminated villages and one arsenic-free village in West Bengal (India) were periodically tested for their ANA titer as well as various

Philippe Belon; Pathikrit Banerjee; Sandipan Chaki Choudhury; Antara Banerjee; Surjyo Jyoti Biswas; Susanta Roy Karmakar; Surajit Pathak; Bibhas Guha; Sagar Chatterjee; Nandini Bhattacharjee; Jayanta Kumar Das; Anisur Rahman Khuda-Bukhsh

63

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

PubMed

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. PMID:20176347

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

2010-05-01

64

Adherence of Blood Components to Artificial Kidney Membranes. (Anti-Nuclear Antibodies in Chronic Dialysis and Renal Transplantation).  

National Technical Information Service (NTIS)

Because of the presence of free cell nuclei and nuclear remnants adherent to used dialysis membranes the authors have studied the prevalence of antibodies to nuclear antigens (DNA, ENA, and FANA) in patients with kidney disease prior to dialysis and patie...

K. D. Nolph G. C. Sharp A. J. Ghods A. W. Siemsen

1977-01-01

65

A retrospective study on IVF/ICSI outcome in patients with anti-nuclear antibodies: the effects of prednisone plus low-dose aspirin adjuvant treatment  

PubMed Central

Background Anti-nuclear antibodies (ANA) are suspected of having relevance to adverse reproductive events. Methods This study aims to investigate the potential effect of ANA on IVF/ICSI outcome and the therapeutic role of prednisone plus low-dose aspirin (P + A) adjuvant treatment in ANA + patients. The first IVF/ICSI cycles without P + A of sixty-six ANA + women were enrolled as the ANA + group, and the 233 first IVF/ICSI cycles of matched ANA- women served as the ANA- group. The ANA + group was divided into the Titre??1:320 subgroup. Twenty-one ANA + women with adverse outcomes in their first cycles (ANA + cycles without P + A) received P + A adjuvant treatment for three months before the second IVF/ICSI cycle (ANA + cycles with P + A). The clinical characteristics and the IVF/ICSI outcomes were compared, respectively, between 1) the ANA + group and the ANA- group, 2) the Titre??1:320 subgroup, and 3) the ANA + cycles without P + A and the ANA + cycles with P + A. Results No significant differences were observed between each of the two-group pairs in the clinical characteristics. The ANA?+?group exhibited significantly lower MII oocytes rate, normal fertilisation, pregnancy and implantation rates, as well as remarkably higher abnormal fertilisation and early miscarriage rates. The Titre??1:320 subgroup. After the P + A adjuvant treatment, the number of two pro-nuclei, perfect embryos and available embryos, and the implantation rate increased significantly. Conclusions These observations suggest that ANA could exert a detrimental effect on IVF/ICSI outcome that might not be titre-dependent, and P + A adjuvant treatment could be useful for ANA + patients. This hypothesis should be verified in further prospective randomised studies.

2013-01-01

66

Distinction between MOG antibody-positive and AQP4 antibody-positive NMO spectrum disorders  

PubMed Central

Objective: To evaluate clinical features among patients with neuromyelitis optica spectrum disorders (NMOSD) who have myelin oligodendrocyte glycoprotein (MOG) antibodies, aquaporin-4 (AQP4) antibodies, or seronegativity for both antibodies. Methods: Sera from patients diagnosed with NMOSD in 1 of 3 centers (2 sites in Brazil and 1 site in Japan) were tested for MOG and AQP4 antibodies using cell-based assays with live transfected cells. Results: Among the 215 patients with NMOSD, 7.4% (16/215) were positive for MOG antibodies and 64.7% (139/215) were positive for AQP4 antibodies. No patients were positive for both antibodies. Patients with MOG antibodies represented 21.1% (16/76) of the patients negative for AQP4 antibodies. Compared with patients with AQP4 antibodies or patients who were seronegative, patients with MOG antibodies were more frequently male, had a more restricted phenotype (optic nerve more than spinal cord), more frequently had bilateral simultaneous optic neuritis, more often had a single attack, had spinal cord lesions distributed in the lower portion of the spinal cord, and usually demonstrated better functional recovery after an attack. Conclusions: Patients with NMOSD with MOG antibodies have distinct clinical features, fewer attacks, and better recovery than patients with AQP4 antibodies or patients seronegative for both antibodies.

Sato, Douglas Kazutoshi; Callegaro, Dagoberto; Lana-Peixoto, Marco Aurelio; Waters, Patrick J.; Jorge, Frederico M. de Haidar; Takahashi, Toshiyuki; Nakashima, Ichiro; Apostolos-Pereira, Samira Luisa; Talim, Natalia; Simm, Renata Faria; Lino, Angelina Maria Martins; Misu, Tatsuro; Leite, Maria Isabel; Aoki, Masashi

2014-01-01

67

Anti-nRNP anti-nuclear antibody-secreting cells are represented in the B-lymphocyte repertoire of normal and MRL/MP-lpr/lpr lupus mice.  

PubMed Central

Spleen cells from MRL-lpr/lpr, CBA and BALB/c mice were cultured in vitro and assayed for production of anti-nuclear antibodies. Spleen cells from all species produced IgM antibodies to a nRNP (U1-RNP)-specific antigen and to double-stranded DNA (dsDNA) after stimulation with LPS. The specificity of the anti-nRNP antibodies was shown, by immunoblotting, to be directed against the 33,000 MW polypeptide of nRNP/Sm. CBA mice produced more IgM autoantibody in vitro than MRL/lpr or BALB/c mice. In contrast, IgG anti-nRNP and anti-dsDNA antibody were not produced by any of the strains. Our data show that anti-nRNP and anti-dsDNA precursor B cells are part of the normal murine immune repertoire and are not confined to the MRL/lpr strain. This suggests that the spontaneous development of anti-nRNP and anti-dsDNA antibodies associated with systemic lupus erythematosis (SLE) is dependent on clonal stimulation and removal of suppressive influences. Images Figure 1

Brennan, F M; Andrew, E M; Williams, D G; Maini, R N

1988-01-01

68

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  

SciTech Connect

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 with 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.

Kilburn, K.H.; Warshaw, R.H. (Univ. of Southern California, Los Angeles (United States))

1992-02-01

69

Ocular symptoms in association with antiphospholipid antibodies  

Microsoft Academic Search

· Objective: To describe the clinical and serologic findings of 50 antiphospholipid antibody (APA)-positive patients within\\u000a a retrospective study.?· Methods: Measurement of visual acuity, slit-lamp biomicroscopy, tonometry, fundus examination and\\u000a perimetry. Laboratory tests were performed for detection of APA against thromboplastin and cardiolipin. Antinuclear antibodies\\u000a (ANA), antibodies to dsDNA, antithyroidal and antiparietal antibodies were also tested.?· Results: A combination of

Beate Leo-Kottler; Reinhild Klein; Peter A. Berg; Eberhart Zrenner

1998-01-01

70

Anti-nuclear fantasies  

SciTech Connect

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 literature 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)

Glynn, P.

1983-01-01

71

Original Approach for Automated Quantification of Antinuclear Autoantibodies by Indirect Immunofluorescence  

PubMed Central

Introduction. Indirect immunofluorescence (IIF) is the gold standard method for the detection of antinuclear antibodies (ANA) which are essential markers for the diagnosis of systemic autoimmune rheumatic diseases. For the discrimination of positive and negative samples, we propose here an original approach named Immunofluorescence for Computed Antinuclear antibody Rational Evaluation (ICARE) based on the calculation of a fluorescence index (FI). Methods. We made comparison between FI and visual evaluations on 237 consecutive samples and on a cohort of 25 patients with SLE. Results. We obtained very good technical performance of FI (95% sensitivity, 98% specificity, and a kappa of 0.92), even in a subgroup of weakly positive samples. A significant correlation between quantification of FI and IIF ANA titers was found (Spearman's ? = 0.80, P < 0.0001). Clinical performance of ICARE was validated on a cohort of patients with SLE corroborating the fact that FI could represent an attractive alternative for the evaluation of antibody titer. Conclusion. Our results represent a major step for automated quantification of IIF ANA, opening attractive perspectives such as rapid sample screening and laboratory standardization.

Bertin, Daniel; Jourde-Chiche, Noemie; Bongrand, Pierre

2013-01-01

72

Impact of pre-transplant Anti-nuclear antibody (ANA) and Anti-smooth muscle antibody (SMA) titers on disease recurrence and graft survival following liver transplantation in autoimmune hepatitis (AIH) patients  

PubMed Central

Background and Aims Disease recurrence following transplant occurs in 20-45% of patients with autoimmune hepatitis. Factors associated with an increased risk of recurrence include HLA DR3 and HLA DR4 positivity, inadequate immunosuppression and severity of inflammation in the native liver. Titers of several auto antibodies can be elevated in patients with autoimmune hepatitis including ANA and SMA however it is unclear whether or not the degree of elevation influences the risk of disease recurrence following transplant. Methods We conducted a retrospective study to evaluate the potential impact of pre transplant titers on post transplant outcomes for patients with autoimmune hepatitis. Sixty three patients with autoimmune hepatitis who underwent 72 liver transplants between January 1, 1989 and January 1, 2009 were included with a median follow up of 104 months. Patients were divided into group A (ANA or SMA ? 1:160) and group B (titers ? 1:160). Results There was no significant difference in recurrence rates or death between patients in group A and B respectively. Only race appeared to impact outcomes with African American patients having a higher incidence of death and recurrent disease post transplant compared to other ethnicities. Conclusions Based on our findings, pre transplant ANA and ASMA levels do not appear to impact recurrence rates or outcomes following liver transplantation for autoimmune hepatitis.

Dbouk, Nader; Parekh, Samir

2012-01-01

73

Adult celiac disease with acetylcholine receptor antibody positive myasthenia gravis  

Microsoft Academic Search

Celiac disease has been associated with some autoimmune disorders. A 40-year-old competitive strongman with celiac disease responded to a gluten- free diet, but developed profound and generalized motor weakness with acetylcholine receptor antibody positive myasthenia gravis, a disorder reported to occur in about 1 in 5000. This possible relationship between myasthenia gravis and celiac disease was further explored in serological

Hugh J Freeman; Helen R Gillett; Peter M Gillett; Joel Oger

2009-01-01

74

Perioperative management of antiphospholipid antibody-positive patients.  

PubMed

Perioperative management of antiphospholipid antibody (aPL)-positive patients is challenging because there are limited data on which to base recommendations. This population of patients is at high risk of thrombosis at the time of surgery; it is essential that medical and surgical teams devise a plan to minimize the patient's risk of thrombosis without increasing bleeding risk. During the perioperative period, pharmacological methods should be combined with physical methods, patients should be closely observed for thrombosis, and any deviation from the normal course should be considered a potential aPL-related event. Periods without anticoagulation should be kept to an absolute minimum for aPL-positive patients with a history of thrombosis and physicians should keep in mind that thrombosis can occur despite optimum prophylaxis. PMID:24828479

Saunders, Katherine H; Erkan, Doruk; Lockshin, Michael D

2014-07-01

75

Anti-DNA antibodies in the primary antiphospholipid syndrome (PAPS)  

PubMed

Primary antiphospholipid syndrome (PAPS) is considered a distinct entity from SLE and patients with PAPS are generally regarded as being dsDNA antibody negative. Levels of IgG and IgM ss and ds DNA antibodies were measured by ELISA in 30 patients who fulfilled the criteria for the diagnosis of PAPS. We compared these patients with 20 normal controls and seven patients with idiopathic SLE. We also examined all the sera for anti-nuclear antibodies by Hep-2 cells and for dsDNA antibodies by Crithidia. We found that 16 patients with PAPS had antibodies to ss and/or dsDNA. Only three of the 16 positive patients had both IgG and IgM anti-DNA antibodies. Twelve patients had anti-nuclear antibodies, but only two were weakly positive for dsDNA antibodies by Crithidia immunofluorescence. Eleven out of 30 patients with PAPS had IgM anti-dsDNA antibodies compared to two out of the seven SLE patients. The PAPS patients with anti-DNA antibodies were clinically indistinguishable from the PAPS patients without antibodies against DNA. Our results show that 53% of patients with PAPS had antibodies to DNA which supports the view that PAPS and SLE are probably overlapping disorders. PMID:8495254

Ehrenstein, M R; Swana, M; Keeling, D; Asherson, R; Hughes, G R; Isenberg, D A

1993-05-01

76

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

PubMed

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

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

77

A monoclonal macroglobulin with antinuclear activity.  

PubMed Central

Serum containing a monoclonal IgM protein from a patient with Waldenstroms' macroglobulinaemia gave intense immunofluorescent staining of kidney nuclei. The Fab mu fragments of this immunoglobulin were obtained. The IgM and Fab fragments reacted in vitro with kidney nuclei using unfixed cryostat sections of rat or mouse kidney. After treatment of the patient with chemotherapy, the monoclonal IgM disappeared, and no more antinuclear activity could be detected in the serum. The results strongly suggest that this IgM protein had antinuclear activity. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5

Intrator, L; Andre, C; Chenal, C; Sultan, C

1979-01-01

78

HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma)  

Microsoft Academic Search

OBJECTIVE--To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). METHODS--HLA class II genes were determined using polymerase chain reaction\\/restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. RESULTS--Frequency of DQB1*0501 was

M Kuwana; Y Okano; J Kaburaki; H Inoko

1995-01-01

79

A strong antibody reacting with enzyme modified E positive red blood cells.  

PubMed

A high titer antibody was discovered in a healthy young man of blood group A1 R2r. The antibody strongly agglutinated all E positive red blood cells including his own, which had been modified by papain, ficin and bromelin, but only very weakly when modified by trypsin. The antibody was shown to be an IgM antibody. It did not react with unmodified red blood cells. PMID:116398

Heistø, H; Fagerhol, M K

1979-01-01

80

A retrospective study of positive antibody screens at delivery in Rh-negative parturients  

Microsoft Academic Search

Purpose  Rhesus- (Rh-) negative women receiving anti-D antibodies antenatally often have a positive antibody screen at delivery. We\\u000a investigated the incidence of positive antibody screens at delivery in this population and examined how the presence of positive\\u000a antibody screens affected the time required to obtain type and screen or type and crossmatch results.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Records of parturients who had type and screen

Christopher R. Cambic; Barbara M. Scavone; Robert J. McCarthy; Paul Eisenberg; Elizabeth M. Sanchez; John T. Sullivan; Cynthia A. Wong

2010-01-01

81

Quantitative Measurement of C6 Antibody following Antibiotic Treatment of Borrelia burgdorferi Antibody-Positive Nonclinical Dogs?  

PubMed Central

The detection of antibody to the Borrelia burgdorferi C6 peptide by use of enzyme-linked immunoassays is a widely accepted method for the diagnosis of Lyme disease spirochete infection in dogs and in humans. Antibody to the C6 peptide is highly specific for B. burgdorferi and declines following treatment of dogs and humans exposed to B. burgdorferi. A quantitative assay for determining C6 antibody levels was developed and used to measure changes in antibody levels following antibiotic treatment of B. burgdorferi antibody-positive nonclinical dogs. One hundred thirty-two client-owned dogs were used in the study; 64 were negative, 53 of 68 positive animals received treatment, and 15 were untreated controls. Test sera were collected at 3, 6, and 12 months from seropositive dogs receiving treatment and untreated controls. Dogs in the treated group were assigned to moderate-to-high (?29 U/ml)- and low (<29 U/ml)-C6-level groups because the change in the C6 level after treatment was dependent on the level prior to treatment. There were significant declines in the 30 dogs with moderate-to-high initial C6 levels that exceeded the maximal declines of the untreated control dogs in all cases at 6 months (16 data points) and 12 months (29 data points) posttreatment. There was little change in C6 level following antibiotic therapy in the 23 dogs with low initial C6 levels. The quantitative C6 antibody test can be used to measure changes in C6 antibody levels following treatment of antibody-positive nonclinical dogs.

Levy, Steven A.; O'Connor, Thomas P.; Hanscom, Jancy L.; Shields, Paulette; Lorentzen, Leif; DiMarco, Anthony A.

2008-01-01

82

Quantitative measurement of C6 antibody following antibiotic treatment of Borrelia burgdorferi antibody-positive nonclinical dogs.  

PubMed

The detection of antibody to the Borrelia burgdorferi C6 peptide by use of enzyme-linked immunoassays is a widely accepted method for the diagnosis of Lyme disease spirochete infection in dogs and in humans. Antibody to the C6 peptide is highly specific for B. burgdorferi and declines following treatment of dogs and humans exposed to B. burgdorferi. A quantitative assay for determining C6 antibody levels was developed and used to measure changes in antibody levels following antibiotic treatment of B. burgdorferi antibody-positive nonclinical dogs. One hundred thirty-two client-owned dogs were used in the study; 64 were negative, 53 of 68 positive animals received treatment, and 15 were untreated controls. Test sera were collected at 3, 6, and 12 months from seropositive dogs receiving treatment and untreated controls. Dogs in the treated group were assigned to moderate-to-high (> or =29 U/ml)- and low (<29 U/ml)-C6-level groups because the change in the C6 level after treatment was dependent on the level prior to treatment. There were significant declines in the 30 dogs with moderate-to-high initial C6 levels that exceeded the maximal declines of the untreated control dogs in all cases at 6 months (16 data points) and 12 months (29 data points) posttreatment. There was little change in C6 level following antibiotic therapy in the 23 dogs with low initial C6 levels. The quantitative C6 antibody test can be used to measure changes in C6 antibody levels following treatment of antibody-positive nonclinical dogs. PMID:18003819

Levy, Steven A; O'Connor, Thomas P; Hanscom, Jancy L; Shields, Paulette; Lorentzen, Leif; Dimarco, Anthony A

2008-01-01

83

False-positive human immunodeficiency virus antibody test in a dialysis patient  

Microsoft Academic Search

A patient developed end-stage renal disease secondary to p-anti-neutrophil cytoplasmic antibody (p-ANCA) positive rapidly progressive glomerulonephritis. He subsequently had human immunodeficiency virus (HIV)-1 antibody screening performed as part of a pre-transplant evaluation. The HIV-1 enzyme immunoassay (EIA) antibody test was repeatedly reactive. The HIV-1 western blot was indeterminate. The western blot pattern revealed “non-specific staining obscuring bands in that region.”

Douglas M. Silverstein; Diego H. Aviles; V. Matti Vehaskari

2004-01-01

84

Antibody Responses to Cryptosporidium Antigen in HIV-positive Patients in the Republic of Korea  

PubMed Central

The diagnosis of cryptosporidiosis has been carried out using coprologic techniques in the Republic of Korea. However, antibody responses to Cryptosporidium have rarely been studied. Serum antibodies from HIV-positive/oocyst-positive Korean patients recognized significantly 31 and 27 kDa antigens, and HIV-negative/oocyst-positive individuals clearly reacted to 15/17 kDa antigens. Compared with oocyst-positive cases, 18.7% and 75.8% of sera from HIV-positive patients reacted to 31 and 27 kDa antigens. Only 11.1% of HIV-negative individuals reacted to 15/17 kDa. Based on these findings, serum antibody responses were different between HIV-positive and HIV-negative individuals infected with Cryptosporidium, and it is suggested that HIV-positive patients are more frequently exposed to C. parvum compared to HIV-negative individuals.

Guk, Sang-Mee; Chai, Jong-Yil; Shin, Yung-Oh

2008-01-01

85

Antimyenteric neuronal antibodies in scleroderma.  

PubMed

The pathogenesis of gastrointestinal (GI) dysmotility in scleroderma is incompletely understood, although previous studies have proposed a neuropathic mechanism. We studied patients with scleroderma as compared with other connective tissue disease patients and normal controls for the presence of circulating antibodies to myenteric neurons. Serial dilutions of sera were overlaid on rat intestine, double-labeled with antineurofilament antibody as a myenteric plexus marker, and imaged using indirect immunofluorescence techniques. High titer sera (> or = 1:50) from 19 out of 41 scleroderma patients stained myenteric neurons, whereas none of 22 normals or 5 patients with idiopathic GI dysmotility were positive. Although 6 out of 20 SLE and 6 out of 10 mixed connective tissue disease patients' sera stained myenteric plexus neurons, when positive sera were absorbed with calf thymus extract to remove antinuclear antibody, 15 scleroderma sera, 0 SLE, and 2 mixed connective tissue disease patients retained positive staining of myenteric neurons. Western blotting using actin and neuronal intermediate filament preparations failed to show immunoreactivity with scleroderma sera containing antimyenteric neuronal antibodies. Paraneoplastic sera associated with GI dysmotility stained myenteric neurons in a different pattern than seen with scleroderma sera. A positive correlation between the presence of Raynaud's phenomenon and antimyenteric neuronal antibodies was observed in scleroderma patients. Our results indicate that IgG antibodies reacting with myenteric neurons are present in many patients with scleroderma. Although the neuronal antigen has not yet been identified, the presence of myenteric neuronal antibodies in patients with GI dysmotility and scleroderma suggests a neuropathic process. PMID:8040331

Howe, S; Eaker, E Y; Sallustio, J E; Peebles, C; Tan, E M; Williams, R C

1994-08-01

86

A Peer Counselling Program for Persons Testing H.I.V. Antibody Positive.  

ERIC Educational Resources Information Center

Describes need for and development of a peer counseling program for persons who have tested positive for human immunodeficiency virus (HIV) antibodies. Discusses selection of peer counselors, training, and confidentiality. Includes discussion of future plans. (ABL)

Baiss, Alan

1989-01-01

87

Trait positive affect and antibody response to hepatitis B vaccination  

Microsoft Academic Search

Recent evidence suggests that dispositional positive affect may be associated with decreased vulnerability to upper respiratory infections. To explore a potential pathway of this relationship, we examined whether trait positive affect is related to an in vivo immune response relevant for host resistance to infection. Eighty-four healthy, graduate students who tested negative for prior expose to the hepatitis B virus

Anna L. Marsland; Sheldon Cohen; Bruce S. Rabin; Stephen B. Manuck

2006-01-01

88

Management of blood donors whose donations are repeatedly falsely positive by the HIV antibody screening test  

Microsoft Academic Search

Since 1985, over 1,800,000 donations have been screened by the West Midlands Regional Blood Transfusion Service for antibody to HIV. Twelve regular donors gave three or more donations that were alternatingly positive and negative in the screening test, but not confirmed to be HIV positive by supplementary testing. Extensive investigation of six of these donors, including the polymerase chain reaction

H I Atrah; J V Parry; D Gough; J Tosswill; F A Ala

1995-01-01

89

21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2010 CFR

...proteins). The measurements aid in the diagnosis of systemic lupus erythematosus (a multisystem autoimmune disease...inflammation of the eye, eyelid, and salivary glands), and systemic sclerosis (chronic hardening and shrinking of...

2009-04-01

90

Arthritis associated with Strongyloides stercoralis infection in a HLA B27-positive African  

Microsoft Academic Search

A 44-year old West-African living in Germany since 18 years presented because of persistent painful swelling of both ankle joints and diffuse lymphoedema of feet occurring after a trip to Morocco. Laboratory tests revealed inflammation and eosinophilia. HLA-B27 was positive. Antinuclear antibodies and rheuma factors were not found. There was no evidence of an infection with bacteria or viruses known to

Joachim Richter; Irmela Müller-Stöver; Harald Strothmeyer; Klaus Göbels; Markus Schmitt; Dieter Häussinger

2006-01-01

91

Musk-antibody positive myasthenia gravis presenting with isolated neck extensor weakness  

Microsoft Academic Search

Dropped head sign is characterized by the gradual forward sagging of the head due to weakness of neck extensor muscles. This may be a prominent sign of several neuromuscular disorders and may be an isolated feature of myasthenia gravis (MG). We describe a patient with isolated neck extensor weakness, eletrophysiological findings suggesting myasthenia gravis and positive MuSK antibodies. This case

C. Casasnovas; M. Povedano; S. Jaumà; J. Montero; J. A. Martínez-Matos

2007-01-01

92

A monoclonal antibody reactive with an activated ras protein expressing valine at position 12.  

PubMed

Activated ras transforming genes have been described in a variety of neoplasms and encode 21,000-Dalton (p21) proteins with amino acid substitutions at positions 12, 13, and 61. In this report we describe a monoclonal antibody designated DWP that reacts specifically with synthetic dodecapeptides containing valine at position 12, to a lesser extent with peptides containing cysteine at position 12 and not with peptides containing glycine, arginine, serine, aspartic acid, glutamic acid or alanine at the same position. Western blot and immunoperoxidase studies showed that DWP specifically reacts with activated rasH or rasK proteins in NIH cells transformed by DNA from the human carcinoma cells that encode valine at position 12. DWP did not react with normal p21s encoding glycine at position 12, nor with activated p21s encoding aspartic acid, glutamic acid, arginine, serine, or cysteine at position 12. A survey of human tumor cell lines demonstrated that DWP reacted with the human bladder carcinoma cell line T24 but not with human tumor cell lines previously shown to contain other activating mutations at positions 12 or 61. DWP and perhaps additional antibodies that specifically react with alterations at positions 12 or 61 of the ras protein may be valuable in determining the presence and frequency of activated ras proteins in human malignancy. PMID:3536974

Carney, W P; Hamer, P; Petit, D; Wolfe, H; Cooper, G; Lefebvre, M; Rabin, H

1986-01-01

93

Antibody variable region glycosylation: position effects on antigen binding and carbohydrate structure.  

PubMed Central

The presence of N-linked carbohydrate at Asn58 in the VH of the antigen binding site of an antibody specific for alpha(1----6)dextran (TKC3.2.2) increases its affinity for dextran 10- to 50-fold. Site-directed mutagenesis has now been used to create novel carbohydrate addition sequences in the CDR2 of a non-glycosylated anti-dextran at Asn54 (TST2) and Asn60 (TSU7). These antibodies are glycosylated and the carbohydrates are accessible for lectin binding. The amino acid change in TSU7 (Lys62----Thr62) decreases the affinity for antigen; however, glycosylation of TSU7 increased its affinity for antigen 3-fold, less than the greater than 10-fold increase in affinity seen for glycosylated TKC3.2.2. The difference in impact of glycosylation could result either from the position of the carbohydrate or from its structure; unlike the other antibodies, TSU7 attaches a high mannose, rather than complex, carbohydrate in CDR2. In contrast, glycosylation of TST2 at amino acid 54 inhibits dextran binding. Thus slight changes in the position of the N-linked carbohydrate in the CDR2 of this antibody result in substantially different effects on antigen binding. Unlike what was observed for the anti-dextrans, a carbohydrate addition site placed in a similar position in an anti-dansyl is not utilized. Images

Wright, A; Tao, M H; Kabat, E A; Morrison, S L

1991-01-01

94

Factors Associated with Serum HCV RNA Positivity in Anti-HCV Antibody Positive Intravenous Drug Users  

Microsoft Academic Search

Serum hepatitis C virus (HCV) RNA, HCV genotypes and liver function tests were evaluated in a series of 189 unselected, consecutive anti-HCV positive intravenous drug users (IVDUs). Serum HCV RNA was detected in 106\\/189 patients. Abnormal liver function tests were associated with alcohol abuse, but not with the presence of serum HCV RNA. Among 109 patients retested after a mean

Mario Pirisi; Pierluigi Toniutto; Carlo Fabris; Tiziana Lombardelli; Edmondo Falleti; Sergio G Tisminetzky; Francisco Baralle; Ettore Bartoli

1998-01-01

95

[Investigation of anticardiolipin antibodies in chronic hepatitis B infection together with total anti-delta positivity].  

PubMed

Anticardiolipin antibodies (ACAs) are formed against phospholipids in various clinical conditions such as autoimmune diseases, malignancy, infectious diseases, alcohol-related and hepatic cirrhosis. The aims of this study were to investigate the presence of ACAs in patients with chronic hepatitis B together with positive total anti-delta antibodies, and to investigate the relationship between age, gender, and some laboratory parameters (ALT, AST, albumin, globulin, platelet number) of patients with chronic hepatitis delta virus (HDV) infection, who were positive or negative for ACAs. A total of 60 patients (43 male, 17 female) with chronic hepatitis D infection [HBsAg positive, HBeAg negative, anti-HBe positive, anti-HBc IgG positive, anti-HBc IgM negative, total anti-delta positive, anti-HCV negative] and 30 patients (21 male, 9 female) without hepatitis D infection [HBsAg positive, HBeAg negative, anti-HBe positive, anti-HBc IgG positive, anti-HBc IgM negative, total anti-delta negative, anti-HCV negative] as control group were included to the study. ACA IgG and IgM were searched by a commercial microELISA kit (Euroimmun, Germany). The statistical evaluation was performed with Pearson's chi-square test, Student's t-test, and Fisher's exact test. Total ACAs positivity rate of 60 patients with chronic HDV infection, was found as 13.3%, in which four of the patients were positive for only ACA IgM, while four was positive for only IgG. Positivity for both ACA IgG and ACA IgM could not be detected in these patients. No patients in the control group had positivity for ACAs (IgG and/or IgM). A statistically significant difference was observed in terms of ACA positivity between patients with and without HDV infection (p< 0.05). After all, there was no statistically significant correlation between ACAs positivity and the age, sex, and laboratory parameters of the patients with chronic HDV infection, except lower serum albumin levels (p= 0.004). Although the data of this study revealed a statistically significant positive correlation between chronic HDV infection and anticardiolipin antibodies, it is clear that there is a need for further studies on this subject. PMID:18822893

Me?e, Sevim; Ozekinci, Tuncer; Atmaca, Selahattin; Arikan, Eralp; Akin, Davut

2008-07-01

96

GST fusion proteins cause false positives during selection of viral movement protein specific single chain antibodies.  

PubMed

Glutathione S-transferase (GST) fusion proteins are used frequently for investigating protein-protein and protein-DNA interactions. The present study demonstrates that the use of GST fusion proteins caused false positives during selection of phage-displayed single-chain antibody fragments (scFvs) specific for three domains of the movement protein (NS(M)) of tomato spotted wilt virus (TSWV). To identify and exclude the false positives when using GST as a fusion partner linked to the antigen of interest, indirect phage enzyme-linked immunosorbent assay (ELISA) was compared with capture phage ELISA. Of 210 enriched phage clones, indirect phage ELISA identified 106 clones specific for binding to GST-domain fusions but not to GST. In contrast, using capture phage ELISA, all 106 selected clones were identified as false positives, reacting with the GST fusion proteins and GST. This was confirmed by characterization of soluble scFv antibodies. The data indicate that GST fusion proteins seem unsuitable for screening of phage-displayed antibody fragments and it is essential to use capture phage ELISA, instead of the indirect phage ELISA used commonly to exclude false positives in characterization of selected clones with GST fusion proteins. PMID:11164495

Zhang, M Y; Schillberg, S; Zimmermann, S; Liao, Y C; Breuer, G; Fischer, R

2001-02-01

97

Low concordance between positive antibodies to thyroperoxidase and thyroid ultrasound autoimmune pattern in pregnant women.  

PubMed

The diagnostic and prognostic role of thyroid ultrasound (TUS) in pregnant women positive for antibodies to thyroperoxidase (TPOAb) is unclear. The aim of our study was to compare the relation of ultrasound thyroid texture to the thyroid laboratory tests in pregnant women and controls. Using a semi-quantitative assessment we compared TUS in two groups of women with positive TPOAb and/or with thyroid dysfunction (TSH out of 0.06-3.67 mIU/L): 186 women in 1(st) trimester of pregnancy recruited from universal screening and 67 asymptomatic age-comparable non-pregnant non-postpartum women recruited from screening of general population (controls). Women with previous history of thyroid diseases were excluded. Only 64/131 (48.9 %) of TPOAb-positive pregnant women were TUS-positive (TUS with autoimmune pattern) in comparison with 35/49 (71.4 %) TPOAb-positive controls (p <0.011). Pregnant women had more often TSH >10.0 mIU/L if they were TPOAb-positive/TUS-positive as compared to those TPOAb-positive/TUS-negative (8/64 (12.5 %) vs. 0/67 (0 %), p = 0.009). The prevalence of preterm deliveries among TPOAb-positive women was significantly lower if TPOAb-positivity was not accompanied by TUS-positivity (2/67 (3.0 %) vs. 10/64 (15.6 %) in TPOAb-positive/TUS-positive women, p = 0.028). In conclusion, nearly half of the TPOAb-positive pregnant women did not have an autoimmune pattern in TUS. Normal TUS image in TPOAb-positive pregnant women might be a protective factor for preterm delivery. PMID:21873803

Jiskra, Jan; Bartáková, Jana; Holinka, Št?pán; Límanová, Zde?ka; Springer, Drahomíra; Fait, Tomáš; Antošová, Marie; Teli?ka, Zden?k; Potluková, Eliška

2011-01-01

98

Studies on production of anticollagen antibodies in silicosis  

SciTech Connect

Silicosis is characterized by pulmonary fibrotic changes which consist primarily of an increase in collagen. In this study, anticollagen antibodies in the serum of 134 silicosis patients versus 40 normal subjects were examined and their relationship with immunoglobulin, autoantibodies, and procollagen III peptide (PIIIP) was investigated by enzyme-linked immunosorbent assay (ELISA). The mean levels of antihuman type I collagen (HI) and anti-human type Ill collagen (HIII) antibodies were significantly higher in the silicosis patients versus the normal subjects (P < 0.001). However, no differences were observed in the mean levels of anti-human type IV collagen (HIV) antibodies in the silicosis patients versus the normal subjects. Anticollagen antibodies in the sera of silicosis patients appear to be formed at an early stage of the disease. We observed a correlation between anticollagen antibodies and immunoglobulin. There was a tendency toward high values of anticollagen antibodies in the sera of patients positive for antinuclear antibodies (ANA) and rheumatoid factor (RF), both of which are autoantibodies. However, no correlation was observed between serum PIIIP and anticollagen antibodies. These observations suggest that, in silicosis, there is a relationship between anticollagen antibodies and immunoglobulins, as well as between anticollagen antibodies and autoantibodies. Measurement of anticollagen antibodies in the sera of silicosis patients offers a useful index for evaluating the prognosis of pulmonary fibrosis and autoimmune abnormality in silicosis. 49 refs. 6 figs., 6 tabs.

Nagaoka, Tadasu; Tabata, Masaji; Kobayashi, Kenichi; Okada, Akira (Kanazawa Univ. (Japan))

1993-01-01

99

[Paraneoplastic limbic encephalitis with positive anti-RI antibodies and mediastinal seminoma].  

PubMed

We report the case of a 49-year-old man who was admitted for progressive behaviorial disorders with frontal elements. There was no sensorial nor motor deficiency. Clinical examination revealed android obesity, cutaneous and mucous paleness, pubic and axillary depilation and gynecomastia. Encephalic MRI found a lesion of the left amygdalian region with high T2 intensity and low T1 intensity associated with gadolinium-enhancement. Cerebrospinal fluid analysis showed a lymphocytic meningitis. Panhypopituitarism was found on the endocrine investigations. Anti-RI antibodies were positive, leading to the diagnosis of paraneoplastic limbic encephalitis. The CT-scan showed a node of the lower part of the thymic area. Surgical resection revealed an ectopic mediastinal seminoma. The evolution consisted of paraneoplastic fever and crossed-syndrome with right hemiparesia and left common oculomotor nerve paralysis. Treatment was completed by two cycles of carboplatin, corticosteroids and substitutive opotherapy. Paraneoplastic fever disappeared, but behavioral disorders and palsy remain unchanged. The patient died two years later in a bedridden state. This case of paraneoplastic limbic encephalitis associated with positive anti-RI antibodies and mediastinal seminoma is exceptional and has not to our knowledge been described in the literature. Cancers usually associated with anti-RI antibody are breast and lung cancer. Paraneoplastic limbic encephalitis is not the classical clinical presentation, which usually is brainstem encephalitis. Hypothalamic involvement, uncommon in paraneoplastic limbic encephalitis is mainly associated with positive antineuronal anti-Ma2 antibodies. Finally, the gadolinium enhancement on encephalic MRI is unusual in paraneoplastic limbic encephalitis. PMID:18565362

Launay, M; Bozzolo, E; Venissac, N; Delmont, E; Fredenrich, A; Thomas, P

2008-01-01

100

Association of genes in the NF-?B pathway with antibody-positive primary Sjögren's syndrome.  

PubMed

Primary Sjögren's syndrome (SS) is a systemic autoimmune inflammatory disease characterized by focal lymphocytic infiltrates in the lachrymal and salivary glands and autoantibodies against the SSA/Ro and SSB/La antigens. Experimental studies have shown an activation of NF-?B in primary SS. NF-?B activation results in inflammation and autoimmunity and is regulated by inhibitory and activating proteins. Genetic studies have shown an association between multiple autoimmune diseases and TNFAIP3 (A20) and TNIP1 (ABIN1), both repressors of NF-?B and of IKBKE (IKK?), which is an NF-?B activator. The aim of this study was to analyse single nucleotide polymorphisms (SNPs) in the IKBKE, NFKB1, TNIP1 and TNFAIP3 genes for association with primary SS. A total of 12 SNPs were genotyped in 1105 patients from Scandinavia (Sweden and Norway, n = 684) and the UK (n = 421) and 4460 controls (Scandinavia, n = 1662, UK, n = 2798). When patients were stratified for the presence of anti-SSA and/or anti-SSB antibodies (n = 868), case-control meta-analysis found an association between antibody-positive primary SS and two SNPs in TNIP1 (P = 3.4 × 10(-5) , OR = 1.33, 95%CI: 1.16-1.52 for rs3792783 and P = 1.3 × 10(-3) , OR = 1.21, 95%CI: 1.08-1.36 for rs7708392). A TNIP1 risk haplotype was associated with antibody-positive primary SS (P = 5.7 × 10(-3) , OR = 1.47, 95%CI: 1.12-1.92). There were no significant associations with IKBKE, NFKB1 or TNFAIP3 in the meta-analysis of the Scandinavian and UK cohorts. We conclude that polymorphisms in TNIP1 are associated with antibody-positive primary SS. PMID:23944604

Nordmark, Gunnel; Wang, Chuan; Vasaitis, Lilian; Eriksson, Per; Theander, Elke; Kvarnström, Marika; Forsblad-d'Elia, Helena; Jazebi, Helmi; Sjöwall, Christopher; Reksten, Tove Ragna; Brun, Johan G; Jonsson, Malin V; Johnsen, Svein J; Wahren-Herlenius, Marie; Omdal, Roald; Jonsson, Roland; Bowman, Simon; Ng, Wan-Fai; Eloranta, Maija-Leena; Syvänen, Ann-Christine

2013-11-01

101

Antibody  

MedlinePLUS

An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples ... as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produced when the immune system mistakenly ...

102

Antibody  

NSDL National Science Digital Library

Antibody: A blood protein that is produced in response to and counteracts an antigen. Antibodies are produced in response to disease and help the body fight against the particular disease. In this way, antibodies help the body develop an immunity to disease.

BEGIN:VCARD VERSION:2.1 FN:Darryl Leja N:Leja;Darryl ORG:National Human Genome Research Institute REV:2005-04-04 END:VCARD

2005-04-04

103

Factors associated with Coxiella burnetii antibody positivity in Danish dairy cows.  

PubMed

The aim of the study was to identify associations between the level of Coxiella burnetii (C. burnetii) antibodies in individual milk samples and cow and herd level factors in Danish dairy cows. The study, designed as a prospective cross sectional study with follow up, included 24 herds identified by a stratified random sampling procedure according to the level of C. burnetii antibodies in one bulk tank milk (BTM) sample at the beginning of the study. Ten herds were BTM positive, ten herds were BTM negative and four herds had an intermediate level. The samples were tested with an ELISA and results determined as S/P (sample to positive control) values. Three cross sectional studies of all lactating cows within each herd were then conducted during an 11 months follow up period with collection of a total of 5829 milk samples from 3116 cows. Each sample was tested with the same ELISA as used for BTM testing, and cows were considered test positive for S/P values ? 40, and otherwise negative. Individual cow information was extracted from the Danish Cattle Database and herd information was obtained from a telephone interview with each farmer. From multivariable logistic regression analysis accounting for hierarchical structures in the data it was concluded that odds for seropositivity increased with Danish Holstein breed, increasing number of parity and high milk protein contents, but decreased with increasing milk yield and high milk fat contents. Cows were at a higher risk during summer than other seasons. Among the herd level factors, herd size, tie stall housing system, quarantine of newly purchased animals and good hygienic precautions taken by the veterinarian before entering into the stable were also significantly associated with reduced odds of C. burnetii antibody positivity. The prevalence of test positive cows was almost constant during the study period in herds which were initially BTM positive and BTM intermediate, whilst the prevalence of positive cows in a few of the initial BTM negative herds changed from almost zero to higher than 60%. This indicates that herd infections last quite long and that test negative herds may convert to positive due to a few latently infected cows or due to transmissions from other herds. PMID:22748360

Paul, Suman; Agger, Jens F; Markussen, Bo; Christoffersen, Anna-Bodil; Agerholm, Jørgen S

2012-11-01

104

Mesothelial Cell and Anti-Nuclear Autoantibodies Associated with Pleural Abnormalities in an Asbestos Exposed Population of Libby MT  

PubMed Central

Despite data linking amphibole asbestos exposure with production of autoantibodies, the role of autoantibodies in subsequent disease is unknown. Residents of Libby, Montana have experienced significant exposure to amphibole asbestos due to the mining of asbestos-contaminated vermiculite near the community over several decades. This population predominantly exhibits pleural disease, and an autoimmune-like disorder that has yet to be well defined. This study sought to determine whether autoantibodies from asbestos-exposed subjects were associated with pleural lesions. Serum samples of subjects from Libby were evaluated for anti-nuclear antibodies (ANA) and mesothelial cell autoantibodies (MCAA) using cell based ELISA. The presence of radiographic abnormalities detected during the time frame of serum collection was determined from screening records. In accord with previous studies, 61.3% (76/124) of the Libby samples were ANA positive, a frequency much higher than expected for a healthy population. The odds of having pleural or interstitial abnormalities in Libby was nearly 3.55 times greater for individuals that tested positive for ANA compared with individuals negative for ANA (p =0.004). MCAA were also detected at a strikingly high frequency (18.5%; 23/124) in samples from Libby. Individuals with MCAA had 4.9 times the risk of having pleural abnormalities compared to MCAA-negative subjects (p=0.044). In conclusion, ANA and MCAA were elevated in a study population that was known to have chronic exposure to asbestos, and these autoantibodies were associated with pleural abnormalities, the predominant finding in the asbestos-exposed population of Libby. Additional research is needed to determine the role these autoantibodies may play in pulmonary disease.

Marchand, Lucas S.; St-Hilaire, Sophie; Putnam, Elizabeth A.; Serve, Kinta M.; Pfau, Jean C.

2011-01-01

105

Segmental Testicular Infarction Due to Minocycline-induced Antineutrophil Cytoplasmic Antibody-positive Vasculitis.  

PubMed

Segmental testicular infarction is an uncommon clinical entity marked by acute scrotal pain and swelling. Classically, these appear as wedge-shaped, avascular, hypoechoic lesions on a testicular ultrasound. We present a unique case of testicular infarct caused by an antineutrophil cytoplasmic antibody-positive vasculitis secondary to the use of the antibiotic minocycline. The patient's symptoms resolved with cessation of minocycline. We suggest that patients who present with otherwise unexplained testicular infarction undergo a careful review of medications to uncover a potential cause. PMID:24793001

Lyon, Timothy D; Ferroni, Matthew C; Casella, Daniel P; D'Agostino, Louis A; Jackman, Stephen V

2014-07-01

106

Quantitative Measurement of C6 Antibody following Antibiotic Treatment of Borrelia burgdorferi Antibody-Positive Nonclinical Dogs  

Microsoft Academic Search

The detection of antibody to the Borrelia burgdorferi C6 peptide by use of enzyme-linked immunoassays is a widely accepted method for the diagnosis of Lyme disease spirochete infection in dogs and in humans. Antibody to the C6 peptide is highly specific for B. burgdorferi and declines following treatment of dogs and humans exposed to B. burgdorferi. A quantitative assay for

Steven A. Levy; Thomas P. O'Connor; Jancy L. Hanscom; Paulette Shields; Leif Lorentzen; Anthony A. DiMarco

2008-01-01

107

A Critical Evaluation of Enzyme Immunoassay Kits for Detection of Antinuclear Autoantibodies of Defined Specificities. III. Comparative Performance Characteristics of Academic and Manufacturers' Laboratories  

Microsoft Academic Search

Objective. To analyze the performance of different commercial enzyme immunoassay (EIA) kits for measuring antinuclear antibodies (ANA) specific for dsDNA, SSB\\/La, Sm, and Scl-70. Methods. EIA kits for detection of ANA from 9 commercial manufacturers were evaluated. The manufacturers were advised that they would be sent coded sera containing mixtures of the Arthritis Foundation\\/Centers for Disease Control reference reagents, and

MARVIN J. FRITZLER; ALLAN WIIK; ENG M. TAN; JOSEF S. SMOLEN; J. STEVEN; EDWARD K. L. CHAN; THOMAS P. GORDON; JOHN A. HARDIN; JOACHIM R. KALDEN; ROBERT G. LAHITA; RAVINDER N. MAINI; WESTLEY H. REEVES; NAOMI F. ROTHFIELD; YOSHINARI TAKASAKI; MERLIN WILSON; MARTHA G. BYRD; LLOYD SLIVKA; JAMES A. KOZIOL

108

Successful treatment with noninvasive positive-pressure ventilation based on the prediction of disease onset using CT and respiratory function tests in an elderly patient with relapsing polychondritis.  

PubMed

An 83-year-old man who had been receiving treatment for bronchial asthma since 62 years of age experienced difficulty breathing on exertion and was admitted to the hospital. On admission, computed tomography revealed tracheal wall thickening, while test results for antinuclear antibodies and anti-type II collagen antibodies were positive. Since a saddle nose deformity, malacia of the auricles and sensorineural deafness were also observed, relapsing polychondritis was diagnosed. Measuring the peak expiratory flow rate was useful in the early airway assessment. During the follow-up period, the patient's dyspnea worsened and noninvasive positive-pressure ventilation was introduced. As a result, the subjective symptoms improved. PMID:23676595

Yamaguchi, Hiromichi; Komase, Yuko; Ono, Ayami; Morita, Akane; Ishida, Akira

2013-01-01

109

Prevalence of antibodies against oxidised LDL in a cohort of 163 patients with positive anti-phospholipid antibodies and recent thrombosis.  

PubMed

We evaluated the prevalence of anti-beta2-glycoprotein I (a-beta2-GPI), anti-phosphatidylserine/prothrombin (a-PP), anti-prothrombin (a-PT), and anti-oxidised low-density lipoprotein (a-oxLDL) antibodies in a cohort of patients with a recent thrombotic event. Among consecutive sera sent to an autoimmune laboratory for routine testing for anti-cardiolipin antibodies (aCL) 473 were found positive for IgG and/or IgM aCL. The referring physicians were requested for clinical information about thrombo-embolic events occurring within 6 months prior to testing. One hundred and sixty-three individuals of which 82 had suffered from cerebro-vascular infarction and 49 from deep venous thromboses or pulmonary emboli were included in the study. Ninety-four sera were positive for IgG aCL and 69 were negative. There was a strong correlation between the presence of IgG aCL and the three other phospholipid-related antibodies: a-beta2-GPI, a-PP, and a-PT. However, IgG a-oxLDL antibodies were almost equally distributed among sera positive and negative for IgG aCL. The presence of antibodies of all subgroups was most pronounced among patients with venous thrombo-embolic disease. In this cohort antibodies to beta2-GPI, PP, PT seem to coexist with aCL. However, a-oxLDL antibodies appear to define a subset of patients, who were older, had more arterial vascular disease, and with no apparent association to the presence of IgG aCL. PMID:16189653

Locht, Henning; Wiik, Allan

2006-03-01

110

Positive Thyroid Peroxidase Antibody Titer is Associated with Dysphoric Moods during Pregnancy and Postpartum  

PubMed Central

Objective To examine general dysphoric moods prospectively in women who tested positive for thyroid peroxidase autoantibodies (TPO) during pregnancy and postpartum. Design Longitudinal, correlational, two group, observational study. Setting Perinatal clinics. Participants Six hundred thirty one (631) pregnant women. Methods Participants were screened for TPO antibodies, and 63 were TPO euthyroid positive. All were asked to continue into a six month postpartum follow up and 47 agreed. A comparison group of TPO negative women (N=72) was randomly selected for follow-up. Women were visited monthly for six months and a blood sample was obtained to measure thyroid stimulating hormone (TSH), a targeted physical exam was conducted, and a thyroid symptom checklist (Perceived Stress Scale) and the Profile of Mood States (POMS) checklist were completed. Results Pregnant TPO positive women had significantly higher depressive symptoms and were more likely to score higher than 20 on the POMS depression scale than TPO negative women. The TPO positive women had significantly higher depression, anger, and total mood disturbance scores postpartum than TOP negative women, regardless of development of postpartum thyroiditis (N=25). Conclusions Our results suggest that the presence of TPO autoantibodies alone in euthyroid pregnant and postpartum women increases the possibility of negative dysphoric moods, especially depressive symptoms that cannot be explained by stress or demographic factors.

Groer, Maureen W.; Vaughan, Jessica H.

2012-01-01

111

Comparison of antibodies that mediate HIV type 1 gp120 antibody-dependent cell-mediated cytotoxicity in asymptomatic HIV type 1-positive men and women.  

PubMed

Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4(+) T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard (51)Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n=32) and the Women's Interagency HIV Study (WIHS; n=32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n=11) and 40.6% (n=13) of men and women, respectively, had titers of 10,000; 62.5% (n=20) and 56.3% (n=18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4(+) T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses (p>0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection. PMID:23972002

Mata, Mariana M; Iwema, Joyce R; Dell, Shanna; Neems, Leslie; Jamieson, Beth D; Phair, John; Cohen, Mardge H; Anastos, Kathryn; Baum, Linda L

2014-01-01

112

Reduction of factor XII in antiphospholipid antibody-positive patients with thrombotic events in the rheumatology clinic  

Microsoft Academic Search

Although rheumatological diagnosis often includes an assessment of antiphospholipid (aPL) antibodies, the significance of\\u000a other prothrombotic factors has not been established in thrombotic patients who are not afflicted with either arteriosclerosis\\u000a or vasculitis syndrome. We have observed both the presence of antiphospholipid antibodies and a reduction of factor XII in\\u000a such patients. Our results identified both lupus anticoagulant-positive (50%) and

M. Takeishi; A. Mimori; K. Nakajima; T. Mimura; T. Suzuki

2003-01-01

113

Antiphospholipid Antibody Syndrome Presenting with Hemichorea  

PubMed Central

A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs) at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120) and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40?mg daily and aspirin 300?mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology.

Ayalew, Yezenash; Khattak, Fazlihakim

2012-01-01

114

Antiphospholipid antibody syndrome presenting with hemichorea.  

PubMed

A 25-year-old Bangladeshi lady presented to neurology with a three-month history of involuntary movements of her right arm, associated with loss of power. There was progression to the right leg, and she subsequently developed episodes of slurred speech and blurred vision. At the time of presentation, she was 12 weeks pregnant and the symptoms were reported to have started at conception. Past medical history was unremarkable apart from one first trimester miscarriage and there was no significant family history suggestive of a hereditary neurological condition. MRI of the head revealed no abnormalities but serology showed positive antinuclear antibodies (ANAs) at a titre of 1/400. Further investigations revealed strongly positive anticardiolipin antibodies (>120) and positive lupus anticoagulant antibodies. The patient had a second miscarriage at 19 weeks gestation strengthening the possibility that the chorea was related to antiphospholipid antibody syndrome and she was started on a reducing dose of Prednisolone 40?mg daily and aspirin 300?mg daily. Six months later, she had complete resolution of neurological symptoms. There are several reports of chorea as a feature of antiphospholipid syndrome, but no clear consensus on underlying pathophysiology. PMID:22937452

Ayalew, Yezenash; Khattak, Fazlihakim

2012-01-01

115

Single-chain antibody/activated BID chimeric protein effectively suppresses HER2-positive tumor growth.  

PubMed

BH3-interacting domain death agonist (BID) is a crucial element in death signaling pathways and is recognized as an intracellular link connecting the intrinsic mitochondrial apoptotic and extrinsic death receptor-mediated apoptotic pathways. Herein, we describe experiments conducted with a fusion protein, which was generated by fusing a human epidermal growth factor receptor-2 (HER2)-specific single-chain antibody with domain II of Pseudomonas exotoxin A and the truncated active BID (tBID). These experiments extend our previous work on several other immuno-proapoptotic proteins. Specifically, by excluding cells with undetectable HER2, we showed that the secreted immuno-tBID molecule selectively recognized and killed HER2-overexpressing tumor cells in vitro by attacking their mitochondria and inducing their apoptotic death. This apoptosis could only be inhibited partially by caspase pan-inhibitor zVAD and mitochondrial protector TAT-BH4. Subsequently, we transferred the immuno-tbid gene into BALB/c athymic mice bearing HER2-positive tumors together with other immuno-proapoptotic proteins using i.m. injections of liposome-encapsulated vectors. The expression of the immuno-tbid gene suppressed tumor growth and prolonged animal survival significantly. We also shortened the translocation domain of Pseudomonas exotoxin A II to only 10-amino acid sequence, which were crucial for furin cleavage. The new recombinant molecule retained the translocation efficiency and the ability of specific killing HER2-positive tumor cells. Our data showed that, compared with the toxins employed before, the chimeric immuno-tBID molecule can not only specifically recognize HER2-positive tumor cells but also certainly induce apoptosis even in the presence of zVAD and TAT-BH4, thereby suggesting an alternative approach to treating HER2/neu-positive tumors. PMID:18644999

Qiu, Xiu-Chun; Xu, Yan-Ming; Wang, Fang; Fan, Qing-Yu; Wang, Li-Feng; Ma, Bao-An; Jia, Lin-Tao; Zhao, Jing; Meng, Yan-Ling; Yao, Li-Bo; Chen, Si-Yi; Yang, An-Gang

2008-07-01

116

Thyroid peroxidase antibody positivity is associated with symptomatic distress in patients with Hashimoto's thyroiditis.  

PubMed

Previous studies suggest impairments of physical, mental, and psychic well-being in patients with Hashimoto's thyroiditis (HT), but these impairments have been shown to be independent of thyroid dysfunction. In 64 euthyroid patients with HT, symptomatic distress was assessed with the Symptom Checklist-90-Revised (SCL-90-R), a 90-item multidimensional self-report symptom inventory using a 5-point rating scale. In a subgroup of patients, endocrine testing 3 years prior to the current investigation was available. Anti-thyroid peroxidase antibodies (TPO-Abs) were associated with the three SCL-90-R global indices Global Severity Index (GSI), Positive Symptom Distress Index (PSDI), and Positive Symptom Total (PST) as well as with somatization and obsessive-compulsive symptoms after adjustment for age, gender, and thyroid function as assessed by TSH levels (all p<0.05). HT patients positive for TPO-Abs showed poorer results in the three SCL-90-R global indices as well as in the three domains: somatization, obsessive-compulsive symptoms, and depression (all p?0.02), though the aforementioned associations did not withstand sequential Bonferroni correction for multiple testing. In contrast, TPO-Abs positivity, defined as TPO-Abs >100 IU/l, significantly predicted poorer psychosocial well-being in all of the three SCL-90-R global indices after three years, even after correction (all p?0.02). In conclusion, high TPO-Abs are associated with poor physical and psychological well-being and appear to predict future health perception in HT patients. PMID:22285302

Müssig, Karsten; Künle, Andreas; Säuberlich, Anna-Laura; Weinert, Claudia; Ethofer, Thomas; Saur, Ralf; Klein, Reinhild; Häring, Hans-Ulrich; Klingberg, Stefan; Gallwitz, Baptist; Leyhe, Thomas

2012-05-01

117

Rheumatic manifestations of euthyroid, anti-thyroid antibody-positive patients.  

PubMed

The aim of this study is to define the rheumatic manifestations of euthyroid patients with chronic lymphocytic thyroiditis (CLT) but without a well-defined connective tissue disease. Forty-six consecutive patients with anti-thyroid peroxidase (?TPO) and/or anti-thyroglobulin antibodies (?TG), and normal thyroid function in the absence of a well-defined connective tissue disease were included in a case-cohort study. Arthralgias were a presenting complaint in 98 % of patients. Fibromyalgia syndrome was found in 59 % of patients. Raynaud's phenomenon occurred in 28 % and sicca symptoms in 26 % of patients. Two patients had seronegative arthritis resembling rheumatoid arthritis. Arthritis was radiographically present in 88 %, affecting the spine in 45 % of patients. Thyroid-stimulating hormone (TSH) levels positively correlated with levels of ?TPO, but not with erythrocyte sedimentation rate (ESR) or ?TG levels. A positive ANA was found in 24 % of patients. One patient developed subclinical hypothyroidism during the study. Rheumatic manifestations frequently occur in patients with CLT in the absence of overt thyroid dysfunction and mimic the presentation of the well-defined connective tissue diseases. PMID:23292189

Tagoe, Clement E; Zezon, Anna; Khattri, Saakshi; Castellanos, Patricia

2013-07-01

118

Antibody depletion for the treatment of crossmatch-positive pediatric heart transplant recipients.  

PubMed

Sensitization to HLA is a risk factor for adverse outcomes after heart transplantation. Requiring a negative prospective CM results in longer waiting times and increased waitlist mortality. We report outcomes in a cohort of sensitized children who underwent transplant despite a positive CDC CM+ using a protocol of antibody depletion at time of transplant, followed by serial IVIG administration. All patients <21 yrs old who underwent heart transplantation at Boston Children's Hospital from 1/1998 to 1/2011 were included. We compared freedom from allograft loss, allograft rejection, and serious infection between CM+ and CM- recipients. Of 134 patients in the cohort, 33 (25%) were sensitized prior to transplantation and 12 (9%) received a CM+ heart transplant. Serious infection in the first post-transplant year was more prevalent in the CM+ patients compared with CM- patients (50% vs. 16%; p = 0.005), as was HD-AMR (50% vs. 2%; p < 0.001). There was no difference in freedom from allograft loss or any rejection. At our center, children transplanted despite a positive CM had acceptable allograft survival and risk of any rejection, but a higher risk of HD-AMR and serious infection. PMID:23919762

Daly, Kevin P; Chandler, Stephanie F; Almond, Christopher S; Singh, Tajinder P; Mah, Helen; Milford, Edgar; Matte, Gregory S; Bastardi, Heather J; Mayer, John E; Fynn-Thompson, Francis; Blume, Elizabeth D

2013-11-01

119

An antibody-cytotoxic conjugate, BIIB015, is a new targeted therapy for Cripto positive tumours.  

PubMed

BIIB015 is an immunoconjugate created for the treatment of solid tumours and is currently in Phase I of clinical evaluation. BIIB015 consists of a humanised monoclonal antibody against the Cripto protein carrying a payload, via a hindered disulphide linker, of the maytansinoid derivative, DM4. Cripto is a GPI-linked protein required for signal transduction of the TGF-beta ligand, Nodal. Cripto has been previously described as an oncogene and fits the classic pattern of an embryonic gene that is re-expressed in a transformed tumour cell. Cripto expression is highly prevalent on a number of solid tumours, including greater than 75% of breast, lung, and colorectal tumours. Our report documents for the first time that targeting the cell surface Cripto protein with an anti-Cripto antibody-cytotoxic conjugate is an effective means of inhibiting or regressing growth of Cripto positive tumours. BIIB015 which utilises a 'cleavable' linker containing a disulphide bond exhibits superior activity when compared to huB3F6 mAb conjugates with different linker systems, including one with a 'non-cleavable' linker. BIIB015 displays specificity for Cripto in both in vitro and in vivo experiments. In human xenograft models originating from lung (Calu-6), colon (CT-3), testicular (NCCIT) and breast (MDA-MB-231) tumour samples, BIIB015 shows robust activity with results ranging from >50% tumour inhibition to complete tumour regression. The efficacy seen in the MDA-MB-231 model, a triple negative (-HER2, -ER, and -PR) tumour, is particularly exciting since there is currently no approved therapy for this indication. In addition, BIIB015 can be combined with standard of care chemotherapeutics for enhanced efficacy. PMID:21458984

Kelly, Rebecca K; Olson, Dian L; Sun, Yaping; Wen, Dingyi; Wortham, Kathleen A; Antognetti, Giovanna; Cheung, Anne E; Orozco, Olivia E; Yang, Lu; Bailly, Veronique; Sanicola, Michele

2011-07-01

120

Green fluorescent-conjugated anti-CEA single chain antibody for the detection of CEA-positive cancer cells.  

PubMed

According to World Health Organization (WHO), cancer is a leading cause of death worldwide, accounting for 7.4 million deaths (around 13% of all deaths) in 2004. Monoclonal/recombinant antibodies, which specifically target clinical biomarkers of disease, have increasingly been applied as powerful tools in cancer imaging and therapy, a fact that is highlighted by some nine FDA-approved monoclonal antibodies (MAbs) or their immunoconjugates (as of December 2008) for use in cancer treatment. In this study, five monoclonal antibodies (MAbs) were generated and characterized against carcinoembryonic antigen (CEA), which is widely used clinically as both a blood and tissue tumor marker of epithelial malignancy. Variable domains (VH and VL) of one the stable MAbs with highest affinity were PCR-amplified and assembled as single-chain antibody fragment (scFv). Following the cloning and expression of scFv antibody fragments in Escherichia coli, the functional binding and specificity of the recombinant antibody were confirmed by ELISA. To develop a direct in vitro detection of CEA-positive cancer cells, scFv DNA was genetically fused to enhanced green fluorescent protein (EGFP) gene and expressed in bacteria. The chimeric fluorescent protein is able to specifically detect CEA-positive cell lines; no cross-reactivity was observed with a negative control cell line. This strategy will likely allow the establishment of a rapid, single-step detection assay of CEA, which is considered to be one of the best predictors of malignancy among all other tumor markers. PMID:21707357

Salavatifar, Maryam; Amin, Shadi; Jahromi, Zahra Moghaddassi; Rasgoo, Nasrin; Rastgoo, Nasrin; Arbabi, Mehdi

2011-06-01

121

Kidney transplantation with positive complement-dependent lymphocytotoxicity crossmatch with negative flow crossmatching and Luminexx donor-specific antibodies.  

PubMed

The presence of positive anti-human, globulin-enhanced, complement-dependent cytotoxicity crossmatches (AHG-CDC-XM) generally has been considered as a contraindication to kidney transplantation (KTx). Flow cytometry crossmatch (FCXM) and solid phase antibody screening are most sensitive and specific methods for immunological assessment. The outcome effect of donor-specific antibody (DSA) positive by Luminexx platform and CDCXM negative has been evaluated,?but not the outcome of CDCXM positive and DSA negative. This is a case report describing KTx in a patient with pre-transplant positive AHG-CDC-XM but negative FCXM and without detectable DSA by Luminexx single antigen beads. CDCXM, FCXM, DSA were negative after transplantation, and kidney allograft biopsy did not show immune injury with negative C4d. Our report suggests that KTx with positive AHG-CDC-XM can be considered if FCXM and DSA were negative with careful immunological monitoring after transplantation. In our case, the IgM-antibodies were responsible for the positive AHG-CDC-XM result. The patient with positive CDC XM has a good outcome in the absence of DSA. Further work is needed to determine under what circumstances CDCXM positive transplants can be performed with FCXM and DSA negative. PMID:23829775

Kute, Vivek B; Vanikar, Aruna V; Gumber, Manoj R; Trivedi, Varsha B; Shah, Pankaj R; Patel, Himanshu V; Balwani, Manish R; Modi, Pranjal R; Trivedi, Hargovind L

2013-08-01

122

Trends in Anti-Nuclear Protests in the United States, 1984-1987.  

National Technical Information Service (NTIS)

This report updates previous RAND research on U.S. anti-nuclear protest groups, examines trends in anti-nuclear and related protests, and assess what these trends may imply for possible terrorist violence, either by terrorists infiltrating the anti-nuclea...

E. H. Ondaatje

1989-01-01

123

Guillain-Barré syndrome-like-onset neurosarcoidosis positive for immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody.  

PubMed

Anti-ganglioside antibodies have been reported in various peripheral neuropathies, including Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, Fisher syndrome, monoclonal gammopathy-associated neuropathy, and other idiopathic neuropathies. To our knowledge, there has been no report of anti-ganglioside-positive sarcoidosis. We report a 62-year-old man with acute weakness of the limbs and sensory disturbance of the right arm and trunk resembling GBS. Soluble interleukin-2 receptor and angiotensin-converting enzyme levels were elevated. Anti-ganglioside antibodies (immunoglobulin G anti-N-acetylgalactosaminyl-GD1a antibody [IgG anti-GalNAc-GD1a antibody]) were detected. Neurophysiological examination demonstrated axonal neuropathy. Bilateral hilar lymphadenopathy was demonstrated on a chest CT scan, and abnormal uptake of 67 Gallium was detected by scintigraphy. The ratio of CD4 to CD8 was elevated in bronchoalveolar lavage fluid. Noncaseating epithelioid cell granulomas were detected in a specimen obtained via transbronchial lung biopsy. Because intravenous immunoglobulin did not improve the symptoms, we commenced steroid pulse therapy followed by oral prednisolone therapy. After steroid therapy, he recovered fully. Because the findings in our patient fulfilled the criteria for neurosarcoidosis, we diagnosed his illness as probable neurosarcoidosis. To the best of our knowledge, this is the first patient with GBS-like-onset neurosarcoidosis positive for anti-IgG anti-GalNAc-GD1a antibody. PMID:23916762

Chatani, H; Tanaka, M; Nagata, T; Araki, T; Kusunoki, S

2014-01-01

124

Small-cell lung cancer with voltage-gated calcium channel antibody-positive paraneoplastic limbic encephalitis: a case report  

PubMed Central

Introduction Paraneoplastic limbic encephalitis is a rare neurological syndrome and clinically characterized by cognitive dysfunction, memory impairment, seizures and psychiatric symptoms. Paraneoplastic limbic encephalitis is most frequently found in small-cell lung cancer, among various malignancies, and antineuronal antibodies are related to the autoimmune mechanism. We experienced a rare case of a patient with small-cell lung cancer with anti-voltage-gated calcium channel antibody-positive paraneoplastic limbic encephalitis. Case presentation A 61-year-old Japanese man with a history of smoking cigarettes presented with seizure, confusion and personality change in acute onset. Brain magnetic resonance imaging showed high signal intensity on T2-weighted image in his right temporal lobe, suggestive of limbic encephalitis. A mediastinoscopy of the lymph node revealed small-cell lung carcinoma, and he was staged as having limited stage disease. Antibodies against P/Q-type and N-type voltage-gated calcium channel were positive and Hu antibody was negative. He was started on chemotherapy of carboplatin plus etoposide with concurrent thoracic radiotherapy. Neurological symptoms were gradually improved after systemic chemotherapy. Conclusions We should be alert to the potential of malignant neoplasms associated with paraneoplastic limbic encephalitis when we examine a patient with cancer with neurological disorders such as personality change, disorientation, unconsciousness and memory loss. A clinical marker such as voltage-gated calcium channel antibody may help our diagnosis in clinical practice.

2014-01-01

125

Incidence of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England, 1993-5  

PubMed Central

Objective: To estimate the rate of seroconversion to positivity for hepatitis C antibody in repeat blood donors in England and to describe the probable routes of infection in these donors. Design: Retrospective survey of blood donors becoming positive for hepatitis C antibody and of the results of donation testing. Setting: The 14 blood centres in England. Subjects: All repeat donors giving blood between January 1993 and December 1995. Main outcome measures: Number of donors developing hepatitis C between donations during the three years of testing for hepatitis C antibody at English blood centres and the rate of seroconversion among repeat blood donors. Probable routes of infection. Results: 14 donors during 1993-5 fulfilled the case definition for seroconversion to positivity for hepatitis C antibody. The estimated seroconversion rate for infection with hepatitis C in repeat donors was 0.26 per 100?000 person years (95% confidence interval 0.15 to 0.43). Counselling after diagnosis found that four of these donors had risk factors specified in the criteria excluding people from giving blood but these factors had not come to light before donation. Another of the donors who seroconverted had a risk factor that has since been included in the exclusion criteria. Heterosexual intercourse was considered to be the most likely route of infection for five of the 14 donors. Conclusions: The rate of seroconversion for positivity to hepatitis C antibody in repeat blood donors in England was extremely low. During 1993-5 fewer than 1 in 450?000 donations were estimated to have come from repeat donors who had become positive for hepatitis C antibody since the previous donation. Key messages The rate of seroconversion for positivity to hepatitis C antibody in English blood donors is low—0.26 per 100?000 person years during 1993-5 (95% confidence interval 0.15 to 0.43) The probable route of infection was unknown in a third of the blood donors who seroconverted during 1993-5 and who provided information on risk factors The exclusion of blood donors with a history of probable exposure to hepatitis C remains an important strategy to help keep the blood supply free of infection

Soldan, K; Barbara, J A J; Heptonstall, J

1998-01-01

126

Systemic auto-antibodies in children with autism.  

PubMed

Autoimmunity to central nervous system may have a role in the pathogenesis of autism. A subset of anti-ds-DNA antibodies has been recently proved to be pathogenic to the brain as well as to the kidney. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of anti-ds-DNA antibodies in a group of autistic children. The seropositivity of anti-nuclear antibodies (ANA) was also investigated. Serum anti-ds-DNA antibodies and ANA were measured in 100 autistic children, aged between 4 and 11years, in comparison to 100 healthy-matched children. The seropositivity of anti-ds-DNA antibodies and ANA in autistic children was 34% and 25%, respectively. In addition, 42% of autistic children were seropositive for anti-ds-DNA antibodies and/or ANA. The frequencies of anti-ds-DNA antibodies and ANA in autistic children were significantly higher than that in healthy children (4% and 2%, respectively), (P<0.001 and P<0.001, respectively). Autistic children with a family history of autoimmunity (45%) had significantly higher frequency of serum anti-ds-DNA antibodies (48.9%) than patients without such a history (21.8%), P=0.008. There was a significant positive association between the seropositivity of anti-ds-DNA antibodies and ANA (P<0.001). In conclusion, anti-ds-DNA antibodies and ANA were found in the sera of a subgroup of autistic children. However, replication studies of larger samples are warranted to validate whether these antibodies are a mere association or have a pathogenic role in some autistic children. PMID:24837704

Mostafa, Gehan A; El-Sherif, Dalia F; Al-Ayadhi, Laila Y

2014-07-15

127

[A case of elderly-onset type 1 diabetes mellitus: negative for antiglutamic acid dehydrogenase antibody and positive insulinoma-associated tyrosine phosphatase-like protein-2 antibody].  

PubMed

An 83-year-old Japanese woman given a diagnosis of type 2 diabetes mellitus 3 years previously was hospitalized for markedly elevated plasma glucose (386 mg/dl) and glycated hemoglobin (9.3%) levels. Laboratory study results showed urinary connecting peptide immunoreactivity (CPR) concentrations of 8.9 ?g/day and serum CPR levels <0.2 ng/ml before and 0.3 ng/ml 6 min after glucagon administration, indicating decreased insulin secretion. Although antiglutamic acid dehydrogenase (GAD) antibody levels were negative, insulinoma-associated tryrosine phosphatase-like protein-2 (IA-2) antibody levels were positive (50 U/ml), leading to a diagnosis of type 1 diabetes mellitus. Furthermore, human leukocyte antigen (HLA) typing revealed DRB1*0901, a diabetes-susceptibility gene. Intensive insulin therapy was initiated. This was a rare case of elderly-onset type 1 diabetes. PMID:23979349

Chiba, Yuko; Ynie, Jeong; Kimbara, Yoshiyuki; Tamura, Yoshiaki; Mori, Seijiro; Ito, Hideki; Araki, Atsushi

2013-01-01

128

Positive dermal hypersensitivity and specific antibodies in workers exposed to bio-engineered enzymes  

SciTech Connect

Thirty-six employees who produced industrial enzymes from bio-engineered strains of bacteria and fungi were evaluated by skin prick testing and enzyme linked immunosorbent assays for specific IgE and IgG antibodies. The workers complained of asthma- and flu-like' symptoms which generally lessened away from work. The enzymes evaluated were {alpha}-amylase from A. niger (ind-AAN), B. licheniformis (ind-AAL) and B. subtilis (ind-AAS); purified {alpha}-amylase from B. subtilis (AAS) and A. niger (AAN); alkaline protease from B. licheniformis (ind-APL) and purified alkaline protease (APL); amylase glucosidase from A. niger (ind-AGN) and purified amylase glucosidase (AGN). Significantly positive skin tests were found for APL, AGN and ind-AAN. Significantly elevated specific IgE results were observed for AAN, AGN, and ind-AAN; elevated specific IgGs were observed for AAN, ind-AAN, ind-AAS, ind-AAL and ind-AGN. Radioimmunoassays of air filter samples (using sera with high Ab titers) for 4 of the ind-enzymes showed only ind-AAN at extremely high environmental levels. These results indicate that occupational exposure to some ind-enzymes causes immediate onset dermal hypersensitivity reactions. The results are equivocal as to whether these reactions are IgE mediated, as IgE titers were low. Contrary to this, IgG titers were extremely high and suggest that these biomarkers can be used as indicators of both individual exposure and environmental analyses.

Biagini, R.E.; Henningsen, G.M.; Driscoll, R.; MacKenzie, B.A.; Wilcox, T.; Scinto, J.D.; Bernstein, D.M.; Swanson, M. (Univ. of Cincinnati, OH (United States) Mayo Clinic, Rochester, MN (United States))

1991-03-15

129

Three-Step Monoclonal Antibody Tumor Targeting in Carcinoembryonic Antigen positive Patients  

Microsoft Academic Search

We describe a method to postlabel, ¡n vivo, biotinylated monoclonal antibodies pretargeted onto tumor deposits when most of the non-tumor- bound antibodies have already been cleared as avidin-bound complexes. The application of this principle to tumor detection by immunoscintig- raphy was tested in 20 patients with histológica!!}documented cancer and increased circulating carcinoembryonic antigen levels. One mg of biotinylated anti-carcinoembryonic antigen

G. Paganelli; P. Magnani; F. Zito; E. Villa; F. Sudati; L. Lopalco; C. Rossetti; M. Malcovati; F. Chiolerio; E. Seccamani; A. G. Siccardi; F. Fazio

1991-01-01

130

Trends in anti-nuclear protests in the United States, 1984-1987  

SciTech Connect

This report updates previous RAND research on U.S. anti-nuclear protest groups, examines trends in anti-nuclear and related protests, and assess what these trends may imply for possible terrorist violence, either by terrorists infiltrating the anti-nuclear movement or violent elements arising within the movement. Two recent trends in protest activity may signal greater militancy in the movement. First, the number of protesters who are willing to face arrest, fines, and imprisonment has steadily increased over the past four years. In the first eleven months of 1987, nearly 3,000 protesters were arrested for anti-nuclear civil disobedience, compared with 1,056 in 1984. Second, some large, diverse groups of protesters have stretched the ability of their own organizers to control events involving civil disobedience. Consequently, the number of skirmishes between protesters and security personnel has increased. Third, radical environmentalist groups previously uninvolved in anti-nuclear activities have recently organized protests at uranium mines. Regular involvement by such groups in anti-nuclear protests, coupled with the trend toward greater cooperation between peace activists and environmentalists over such issues as uranium mining, nuclear testing, land and sea use, and transport and storage of toxic waste, could signal a more volatile, though not necessarily more violent, future for the anti-nuclear movement.

Ondaatje, E.H.

1989-01-01

131

Central retinal vein occlusion in a pediatric patient with SLE and antiphospholipid antibodies without anti-cardiolipin or anti-?2 glycoprotein I antibodies  

PubMed Central

Background Antiphospholipid antibody syndrome is characterized by venous and/or arterial thrombosis, and is found in patients with systemic lupus erythematosus. Its diagnosis requires the presence of both clinical and laboratory findings, such as positive anti-cardiolipin and anti-?2 glycoprotein I antibodies and lupus anticoagulant. However, cardiolipin is a minor component of the vascular endothelial cells in human, and phosphatidylcholine and phosphatidylethanolamine are major components. Case presentation A 15-year-old female suddenly developed massive left intraretinal hemorrhaging due to central retinal vein occlusion. She also had a butterfly rash, and her laboratory findings revealed positive serum anti-nuclear antibodies and decreased serum complement. During this episode, she was diagnosed with systemic lupus erythematosus. Although she was negative for serum anti-cardiolipin IgG and anti-?2 glycoprotein I antibodies as well as lupus anticoagulant, her serum anti-phosphatidylcholine, anti-phosphatidylethanolamine, anti-phosphatidylinositol and phosphatidylserine IgG antibodies levels were increased. Conclusion Pediatric cases of central retinal vein occlusion are rare. Even in patients without anti-cardiolipin or anti-?2 glycoprotein I antibodies and lupus anticoagulant, there is the potential for the development of antiphospholipid antibody-related thrombosis.

2014-01-01

132

A case of propylthiouracil-induced antineutrophilic cytoplasmic antibody-positive vasculitis successfully treated with radioactive iodine.  

PubMed

Antineutrophilic cytoplasmic antibody (ANCA) associated vasculitis is one of the rare complications of propylthiouracil treatment. Having a variable clinical spectrum, it may be presented with both skin limited vasculitis and life-threatening systemic vasculitis. In this study, we present a case that developed ANCA-positive vasculitis with skin and kidney involvement (hematuria and proteinuria) six months after propylthiouracil treatment was initiated for toxic nodular goiter. Proteinuria recovered dramatically subsequent to radioactive iodine treatment following ceasing the drug. PMID:23884029

Bes, C; Dikba?, O; Keskin, E; Kaptano?ullar?, Ö; Soy, M

2013-01-01

133

Multiplex analysis of expression of three IFNbeta-induced genes in antibody-positive MS patients.  

PubMed

Some interferon beta (IFNbeta)-treated patients with multiple sclerosis develop antibody-mediated decreased bioactivity with resultant loss of therapeutic effect. The authors developed real-time multiplex reverse transcriptase PCR to measure expression of three IFNbeta-inducible genes to directly assess IFNbeta bioactivity in patients with neutralizing antibodies (NAbs). The three genes responded in tandem. Correlation of NAb level with bioactivity at low/moderate NAb levels was poor, indicating that for such patients, direct measurement of IFNbeta bioactivity is most reliable. PMID:16476953

Pachner, Andrew R; Narayan, Kavitha; Pak, Elena

2006-02-14

134

Antineutrophil cytoplasmatic antibody positive systemic vasculitis in a patient treated with propylthiouracil.  

PubMed

The development of antineutrophil cytoplasmatic antibody (ANCA) during therapy with propylthiouracil (PTU) is not uncommon but occasionally has clinical significance. Risk factors associated with the development of ANCA associated systemic vasculitis when taking PTU have been described. We report and discuss a case with PTU-induced ANCA vasculitis with severe systemic manifestations. PMID:24435037

Silva, Sara Vieira; Ferreira, João Pedro; Carvalho, Sandrine; Seabra, Filipa; Marinho, António

2013-01-01

135

Biological Evaluation of 131I- and CF750-Labeled Dmab(scFv)-Fc Antibodies for Xenograft Imaging of CD25-Positive Tumors  

PubMed Central

A Dmab(scFv)-Fc antibody containing the single chain variable fragment of a humanized daclizumab antibody and the Fc fragment of a human IgG1 antibody was produced via recombinant expression in Pichia pastoris. The Dmab(scFv)-Fc antibody forms a dimer in solution, and it specifically binds CD25-positive tumor cells and tumor tissues. For tumor imaging, the Dmab(scFv)-Fc antibody was labeled with the 131I isotope and CF750 fluorescent dye, respectively. After intravenous injection of mice bearing CD25-positive tumor xenografts, tumor uptake of the 131I-Dmab(scFv)-Fc antibody was visible at 1?h, and clear images were obtained at 5?h using SPECT/CT. After systemic administration of the CF750-Dmab(scFv)-Fc antibody, tumor uptake was present as early as 1?h, and tumor xenografts could be kinetically imaged within 9?h after injection. These results indicate that the Dmab(scFv)-Fc antibody rapidly and specifically targets CD25-positive tumor cells, suggesting the potential of this antibody as an imaging agent for the diagnosis of lymphomatous-type ATLL.

Fan, Qing; Cai, Huawei; Yang, Hao; Li, Lin; Yuan, Cen; Lu, Xiaofeng; Wan, Lin

2014-01-01

136

Anti-GAD antibody positive stiff-limb syndrome in multiple myeloma.  

PubMed

Although most cases of stiff-limb syndrome are unassociated with malignancy, occasional cases have been associated with breast and lung cancer. Only four reported patients have had cancer and stiff-limb syndrome associated with anti-GAD antibodies. We report the first case of stiff-limb syndrome in a patient with multiple myeloma undergoing treatment with thalidomide, and explore the potential link to the cancer and its treatment. PMID:14686738

Schiff, David; Dalmau, Josep; Myers, Delynne J

2003-11-01

137

Radiolocalization of human small cell lung cancer and antigen-positive normal tissues using monoclonal antibody LS2D617  

SciTech Connect

The murine monoclonal antibody LS2D617, which reacts with an antigen associated with human small cell lung carcinoma (SCLC), was tested in preclinical models to assess its potential for specific targeting of tumors in human SCLC cancer patients. LS2D617 detects a cell antigen on the surface of cultured SCLC and neuroblastoma cell lines. Scatchard analysis of the binding of LS2D617 to NCIH69 SCLC cells indicates an affinity constant of about 1 x 10(8) M-1 and an epitope expression level of approximately 2 x 10(6) antigenic sites/cell. Molecular weight analysis of the target antigen and antibody competition experiments showed that LS2D617 should be classified as a SCLC Cluster 1 antibody. LS2D617 was labeled with 111In and tested for biodistribution (4, 24, 48, 72, and 96 h postinjection) in nude mice bearing the human SCLC NCIH69 tumor. Tumor values peaked at about 35% injected dose/g (Day 3) compared with about 8% injected dose/g for an irrelevant IgG1 antibody while normal tissue accumulation for both antibodies was about 2-8% injected dose/g. Immunohistochemical studies demonstrated that LS2D617 reacts with the central nervous system, peripheral nerves, endocrine tissues, and heart tissue of rabbits as it does in human tissues. The ability of LS2D617 to accumulate in vivo in normal tissues that express the specific target antigen was tested in rabbits. Rabbits given i.v. injections of 111In-LS2D617 or control labeled antibody were sacrificed at 48 h and tissues were examined by gamma well counting, autoradiography, and immunohistochemical staining for murine immunoglobulin. Specific uptake was seen in all sites defined as antigen positive by immunohistology (i.e., heart, liver bile duct, peripheral nerves, pituitary, adrenal), except the central nervous system (brain and spinal cord) which was inaccessible to antibody because of the blood brain barrier.

Wilson, B.S.; Petrella, E.; Lowe, S.R.; Lien, K.; Mackensen, D.G.; Gridley, D.S.; Stickney, D.R. (Hybritech Inc., San Diego, CA (USA))

1990-05-15

138

Detectability of Her2 positive tumors using monoclonal antibody conjugated iron oxide nanoparticles in MRI.  

PubMed

Detecting an imaging signal from a small number of cells is vital when a disease needs to be diagnosed in an early stage of development. Molecular and genetic information from cancer cell types provide a guide for specific imaging based on gene expression and their activities on the cell membrane. Various physical and biological parameters affect the capability of an imaging system to provide an efficient procedure for biomarker imaging. Iron oxide based magnetic nanoparticles conjugated to breast cancer monoclonal antibody (Her2) were used as a specific contrast agent for detection of the tumor cells in nude mice models. All processes for the nanoparticle synthesis, antibody development, and conjugation strategies were designed and evaluated in the current work. The final engineered product was found to be without precipitate containing 20 microg antibody/mg magnetic nanoparticles at 10 mg Fe/ml solution. This contrast agent has a high affinity for the BT474 breast cancer cells. MRI images of nude mice bearing tumor cells confirm this specific biomarker based imaging protocol. PMID:21770186

Oghabian, M A; Jeddi-Tehrani, M; Zolfaghari, A; Shamsipour, F; Khoei, S; Amanpour, S

2011-06-01

139

Clonal analysis of liver-infiltrating T cells in patients with LKM-1 antibody-positive autoimmune chronic active hepatitis.  

PubMed Central

Autoantibodies against microsomal antigen of liver and kidney (LKM-1) are diagnostic markers for a subgroup of autoimmune chronic active hepatitis (AI-CAH). Cytochrome P450dbl, now classified as cytochrome P450 IID6, is the major antigen of LKM-1 antibodies. Immunohistological studies suggest that hepatic injury in AI-CAH is mediated by liver-infiltrating T cells. In the present study the specificity and function of liver-infiltrating T cells was analysed at the clonal level. Phenotypical characterization of 189 T cell clones isolated from four liver biopsies of LKM-1 antibody-positive patients showed an enrichment of CD4+ CD8- T cell clones proliferated specifically in the presence of recombinant human LKM-1 antigen (rLKM). This reaction was restricted to autologous antigen-presenting cells and to HLA class II molecules. In order to see whether rLKM was also recognized by peripheral blood T lymphocytes (PBL) we tested the proliferative response of PBL from several individuals. PBL from three of the four patients with LKM-1 antibody-positive AI-CAH proliferated to rLKM, whereas no response was seen with PBL from patients with LKM-1 antibody-negative chronic liver diseases and from healthy blood donors. These data demonstrate that the LKM-1 antigen is recognized by liver-infiltrating T cells in LKM-1 antibody-positive AI-CAH. For further functional characterization, liver-derived T cell clones were tested for their cytotoxic activity. In the presence of phytohaemagglutinin 24 out of 26 CD4- CD8+ but also 20 out of 63 CD4+ CD8- T cell clones lysed autologous as well as allogenic EBV-transformed B cell lines or K562 cells. Five CD4- CD8+ T cell clones lysed autologous but not allogenic B cell lines spontaneously in a HLA class I-restricted manner. Although the antigen specificity of these clones is still unknown the data show the presence of autoreactive T cells at the site of inflammation that could contribute in the pathogenesis of AI-CAH.

Lohr, H; Manns, M; Kyriatsoulis, A; Lohse, A W; Trautwein, C; Meyer zum Buschenfelde, K H; Fleischer, B

1991-01-01

140

HLA-DRB1 Genotypes and the Risk of Developing Anti Citrullinated Protein Antibody (ACPA) Positive Rheumatoid Arthritis  

PubMed Central

Objective To provide a table indicating the risk for developing anti citrullinated protein antibody (ACPA) positive rheumatoid arthritis (RA) according to one’s HLA-DRB1 genotype. Methods We HLA-DRB1 genotyped 857 patients with ACPA positive RA and 2178 controls from South Eastern and Eastern France and calculated Odds Ratios (OR) for developing RA for 106 of 132 possible genotypes accounting for 97% of subjects. Results HLA-DRB1 genotypic ORs for developing ACPA positive RA range from 28 to 0.19. HLA-DRB1 genotypes with HLA-DRB1*04SE (HLA-DRB1*0404, HLA-DRB1*0405, HLA-DRB1*0408), HLA-DRB1*04?01, HLA-DRB1*01 are usually associated with high risk for developing RA. The second HLA-DRB1 allele in genotype somewhat modulates shared epitope associated risk. We did not identify any absolutely protective allele. Neither the Reviron, nor the du Montcel models accurately explains our data which are compatible with the shared epitope hypothesis and suggest a dosage effect among shared epitope positive HLA-DRB1 alleles, double dose genotypes carrying higher ORs than single dose genotypes. Conclusion HLA-DRB1 genotypic risk for developing ACPA positive RA is influenced by both HLA-DRB1 alleles in genotype. We provide an HLA-DRB1 genotypic risk table for ACPA positive RA.

Balandraud, Nathalie; Picard, Christophe; Reviron, Denis; Landais, Cyril; Toussirot, Eric; Lambert, Nathalie; Telle, Emmanuel; Charpin, Caroline; Wendling, Daniel; Pardoux, Etienne; Auger, Isabelle; Roudier, Jean

2013-01-01

141

The use of antibody to C5b-9 in the subclassification of lupus erythematosus.  

PubMed

Fifty-five patients with biopsy-proven cutaneous lupus erythematosus (LE) were identified in whom a prospective and retrospective review of the clinical and laboratory data allowed subclassification into systemic (SLE), subacute (SCLE), or discoid (DLE) variants. In addition to conventional direct immunofluorescence, an indirect immunofluorescent technique, using a monoclonal antibody, was employed to assess deposition of the membranolytic attack complex (C5b-9) in skin lesions. Deposition of C5b-9 within the epidermis correlated with a diagnosis of SCLE with or without antibodies to Ro and was seen in SLE patients with antibodies to extractable nuclear antigens Ro, La, Sm, and RNP, and in DLE patients with positive antinuclear antibodies and/or extracutaneous manifestations. In the SLE group, vascular C5b-9 deposition was present in six patients. Of these, four had circulating lupus anticoagulant, one had lymphocytic vasculitis, and two had antibodies to Ro. In two patients with SLE there was keratinocyte decoration for immunoglobulin G but not for C5b-9, in the absence of seropositivity for antibodies to Ro, La, Sm, and ribonucleoprotein (RNP). The immunohistological examination of skin lesions using a monoclonal antibody to C5b-9 is a valuable adjunct in the subclassification of LE. The presence of C5b-9 within skin lesions of patiens with LE implies a pathogenic role for complement-mediated pore formation. PMID:8736325

Magro, C M; Crowson, A N; Harrist, T J

1996-05-01

142

Alpha-Galactosyl trisaccharide epitope: Modification of the 6-primary positions and recognition by human anti-alphaGal antibody.  

PubMed

Galactose oxidase (EC 1.1.3.9, GAO) was used to convert the C-6' OH of Galbeta(1 --> 4)Glcbeta-OBn (5) to the corresponding hydrated aldehyde (7). Chemical modification, through dehydratative coupling and reductive amination, gave rise to a small library of Galbeta(1 --> 4)Glcbeta-OBn analogues (9a-f, 10, 11). UDP-[6-(3)H]Gal studies indicated that alpha1,3-galactosyltransferase recognized the C-6' modified Galbeta(1 --> 4)Glcbeta-OBn analogues (9a-f, 10, 11). Preparative scale reactions ensued, utilizing a single enzyme UDP-Gal conversion as well as a dual enzymatic system (GalE and alpha1,3GalT), taking full advantage of the more economical UDP-Glc, giving rise to compounds 6, 15-22. Galalpha(1 --> 3)Galbeta(1 --> 4)Glcbeta-OBn trisaccharide (6) was produced on a large scale (2 g) and subjected to the same chemoenzymatic modification as stated above to produce C-6" modified derivatives (23-30). An ELISA bioassay was performed utilizing human anti-alphaGal antibodies to study the binding affinity of the derivatized epitopes (6, 15-30). Modifications made at the C-6' position did not alter the IgG antibody's ability to recognize the unnatural epitopes. Modifications made at the C-6" position resulted in significant or complete abrogation of recognition. The results indicate that the C-6' OH of the alphaGal trisaccharide epitope is not mandatory for antibody recognition. PMID:15001843

Andreana, Peter R; Kowal, Przemyslaw; Janczuk, Adam J; Wang, Peng George

2004-01-01

143

Multiple cranial nerve palsy revealing hypertrophic pachymeningitis with positive myeloperoxidase-antineutrophil cytoplasmic antibody.  

PubMed

Pachymeningitis is a progressive disease resulting in a diffuse thickening of dura mater due to inflammation, tumor or autoimmune diseases, but most cases are idiopathic. Here, we report the case of a 60-year old man who had a progressive sensorineural hearing loss, visual disturbance and others cranial nerve involvement with an accompanying headache over several months. Brain magnetic resonance imaging showed diffusely thickened dura mater, highly enhanced after gadolinium administration, which was consistent with pachymeningitis. It was assumed to be related to autoimmune pathogenesis on the basis of elevated serum myeloperoxidase-antineutrophil cytoplasmic antibody titers. After empirical steroid and cyclophosphamide therapy, the neurological problems were partially improved. Therefore, in the case of atypical sensorineural hearing loss accompanied by cranial nerve palsy or headache, pachymeningitis should be considered in the differential diagnosis. PMID:24399188

El Aoud, S; Frikha, F; Ben Salah, R; Snoussi, M; Loukil, H; Bahloul, Z

2013-01-01

144

Clinical Phenotypes of Patients with Anti-DFS70/LEDGF Antibodies in a Routine ANA Referral Cohort  

PubMed Central

Objective. To analyze the clinical value of anti-DFS70 antibodies in a cohort of patients undergoing routine antinuclear antibodies (ANAs) testing. Methods. Sera with a dense fine speckled (DFS) indirect immunofluorescence (IIF) pattern from 100 consecutive patients and 100 patients with other IIF patterns were tested for anti-DFS70 antibodies by a novel chemiluminescence immunoassay (CIA) and for ANA by ANA Screen ELISA (both INOVA). Results. Among the 100 patients with a DFS IIF pattern, 91% were anti-DFS70 positive by CIA compared to 3% in the comparator group (P < 0.0001). The CIA and IIF titers of anti-DFS antibodies were highly correlated (rho = 0.89). ANA by ELISA was positive in 35% of patients with the DFS IIF pattern as compared to 67% of patients with other patterns (P < 0.0001). Only 12.0% of patients with DFS pattern and 13.4% with DFS pattern and anti-DFS70 antibodies detected by CIA had systemic autoimmune rheumatic disease (SARD). Only 5/91 (5.5%) patients with anti-DFS70 antibodies had SARD and their sera were negative on the ANA Screen ELISA. Conclusion. Although anti-DFS70 antibodies cannot exclude the presence of SARD, the likelihood is significantly lower than in patients with other IIF patterns and should be included in test algorithms for ANA testing.

Miyara, Makoto; Albesa, Roger; Charuel, Jean-Luc; El Amri, Mohamed; Fritzler, Marvin J.; Ghillani-Dalbin, Pascale; Amoura, Zahir; Musset, Lucile; Mahler, Michael

2013-01-01

145

In silico Driven Redesign of a Clinically Relevant Antibody for the Treatment of GD2 Positive Tumors  

PubMed Central

Ganglioside GD2 is a cell surface glycolipid that is highly expressed on cancer cells of neuroectodermal origin, including neuroblastoma, retinoblastoma, melanoma, sarcomas, brain tumors and small cell lung cancer. Monoclonal antibodies (MoAb) that target GD2 have shown clinical efficacy in the treatment of GD2 expressing tumors, and are expected to be the new standard of care for the treatment of pediatric neuroblastoma. In this study, the crystal structure of anti-GD2 murine MoAb 3F8 was solved to 1.65 Å resolution and used as a template for molecular docking simulations of its antigen, the penta-saccharide head group of GD2. Molecular docking revealed a binding motif composed of 12 key interacting amino acid side-chains, involving an extensive network of interactions involving main-chain and side-chain hydrogen bonding, two Pi – CH interactions, and an important charged interaction between Arg95 of the H3 loop with the penultimate sialic acid residue of GD2. Based on in silico scanning mutagenesis of the 12 interacting amino acids from the docked 3F8:GD2 model, a single point mutation (Heavy Chain: Gly54Ile) was engineered into a humanized 3F8 (hu3F8) MoAb and found to have a 6–9 fold enhancement in antibody-dependent cell-mediated cytotoxicity of neuroblastoma and melanoma cell lines. With enhanced tumor-killing properties, the re-engineered hu3F8 has the potential be a more effective antibody for the treatment of GD2-positive tumors.

Ahmed, Mahiuddin; Goldgur, Yehuda; Hu, Jian; Guo, Hong-Fen; Cheung, Nai-Kong V.

2013-01-01

146

No detectable precolostral antibody response in calves born from cows with cotyledons positive for Coxiella burnetii by quantitative PCR.  

PubMed

Samples from 45 dams (milk/colostrum, faeces, vaginal fluid and blood on days 171-177 of gestation and at parturition, and cotyledons at parturition) and their calves (blood collected before colostrum intake and weekly until days 29-35) were analysed to examine the vertical transmission of Coxiella burnetii and links between shedding and seropositivity. All calves were born C. burnetii seronegative. Only those born to seropositive dams seroconverted following colostrum intake. Logistic regression analyses indicated that the likelihood of dam seropositivity was 21 and 4.85 times higher for multiparous than for primiparous (65.6% vs. 8.3%, P = 0.006) and for prepartum shedding cows (75% vs. 38.2%, P = 0.03) compared to the remaining animals, respectively. In conclusion, the results of this study indicate no detectable precolostral antibody response in calves born from dams with cotyledons positive for C. burnetii by qPCR. In order to analyse the possibility of persistent infection due to immunotolerance to an early in utero infection, further studies will need to test for C. burnetii DNA. In addition, in the present study multiparous cows showed a significantly higher seroprevalence than primiparous cows and heifers, colostral antibodies were efficiently transferred to newborn calves, and there was a link between bacterial shedding on days 171-177 of gestation and Coxiella seropositivity of the dam. PMID:23974927

Tutusaus, Joan; López-Gatius, Fernando; Almería, Sonia; Serrano, Beatriz; Monleón, Eva; José Badiola, Juan; García-Ispierto, Irina

2013-12-01

147

Clinical and Electrophysiologic Responses to Acetylcholinesterase Inhibitors in MuSK-Antibody-Positive Myasthenia Gravis: Evidence for Cholinergic Neuromuscular Hyperactivity  

PubMed Central

Background and Purpose Patients with muscle-specific tyrosine kinase (MuSK) antibody (MuSK-Ab)-positive myasthenia gravis (MG) show distinct responses to acetylcholinesterase inhibitors (AChEIs). Although clinical responses to AChEIs in MuSK-Ab MG are reasonably well known, little is known about the electrophysiologic responses to AChEIs. We therefore investigated the clinical and electrophysiologic responses to AChEIs in MuSK-Ab-positive MG patients. Methods We retrospectively reviewed the medical records and electrodiagnostic findings of 17 MG patients (10 MuSK-Ab-positive and 7 MuSK-Ab-negative patients) who underwent electrodiagnostic testing before and after a neostigmine test (NT). Results The frequency of intolerance to pyridostigmine bromide (PB) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (50% vs. 0%, respectively; p=0.044), while the maximum tolerable dose of PB was lower in the former (90 mg/day vs. 480 mg/day, p=0.023). The frequency of positive NT results was significantly lower in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (40% vs. 100%, p=0.035), while the nicotinic side effects of neostigmine were more frequent in the former (80% vs. 14.3%, p=0.015). Repetitive compound muscle action potentials (R-CMAPs) developed more frequently after NT in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (90% vs. 14.3%, p=0.004). The frequency of a high-frequency-stimulation-induced decrement-increment pattern (DIP) was higher in MuSK-Ab-positive patients than in MuSK-Ab-negative patients (100% vs. 17.7%, p=0.003). Conclusions These results suggest that MuSK-Ab-positive MG patients exhibit unique and hyperactive responses to AChEIs. Furthermore, R-CMAP and DIP development on a standard AChEI dose may be a distinct neurophysiologic feature indicative of MuSK-Ab-positive MG.

Shin, Ha Young; Park, Hyung Jun; Lee, Hyo Eun; Choi, Young-Chul

2014-01-01

148

Antibody-directed double suicide gene therapy targeting of MUC1- positive leukemia cells in vitro and in vivo.  

PubMed

Our aim was to specifically transfer the cytosine deaminase (CD) and thymidine kinase (TK) genes into mucin 1 (MUC1)-positive leukemia cells by anti-MUC1 antibody directed infection of replication-defective lentivirus and to evaluate the targeted cytotoxicity of double suicide genes to leukemia. The target gene vector (containing CD and TK) and envelope (containing GFP and anti-MUC1) and packaging plasmids were cotransfected into 293T cells to produce the recombinant lentivirus. Suicide genes in virus-infected leukemia cells (U937, Jurkat, and K562) were detected by western blot. The cytotoxicity and bystander effect in vitro and the therapeutic effect in vivo were detected after treatment with the prodrugs. The results revealed that combined treatment with prodrug 5-fluorocytosine (5-FC) and ganciclovir (GCV) inhibited leukemia cell growth and caused significant bystander effect than treatment with either prodrug alone. TK/GCV treatment alone induced degeneration and cell death while the effect of CD/5-FC alone mainly caused vacuolar degeneration and necrosis. The addictive effects of combinatorial use of GCV and 5-FC mainly induced swelling of the mitochondria followed by necrosis of the leukemia cells. In vivo experiments revealed that both single and combinatorial prodrug treatments could prolong the survival time of leukemic mice. In summary, anti-MUC1 antibody directed lentiviral vector successfully transduced dual suicide genes and exerted targeted cytotoxicity against MUC1 positive leukemia cells. This targeted lentiviral dual suicide gene delivering system provides a promising approach for clinical treatment of leukemia in future. PMID:24060312

Dong, Xiao-Ya; Wang, Wen-Qian; Zhao, Yu; Li, Xu-Dong; Fang, Zhi-Gang; Lin, Dong-Jun; Xiao, Ruo-Zhi; Huang, Ren-Wei; Pan, Guang-Jin; Liu, Jia-Jun

2013-10-01

149

Antibodies to hepatitis B surface antigen prevent viral reactivation in recipients of liver grafts from anti-HBC positive donors  

PubMed Central

Background and aims: Liver donors with serological evidence of resolved hepatitis B virus (HBV) infection (HBV surface antigen (HBsAg) negative, anti-HBV core (HBc) positive) can transmit HBV infection to recipients. In the context of organ shortage, we investigated the efficacy of hepatitis B immunoglobulin (HBIG) to prevent HBV infection, and assessed the infectious risk by polymerase chain reaction (PCR) testing for HBV DNA on serum and liver tissue of anti-HBc positive donors. Patients: Between 1997 and 2000, 22 of 315 patients were transplanted with liver allografts from anti-HBc positive donors. Long term HBIG therapy was administered to 16 recipients. Four naive and two vaccinated patients received no prophylaxis. Results: Hepatitis B developed in the four HBV naive recipients without prophylaxis and in none of the vaccinated subjects. Among the 16 recipients receiving HBIG, one patient with residual anti-HBs titres below 50 UI/ml became HBsAg positive. The remaining 15 remained HBsAg negative and HBV DNA negative by PCR testing throughout a 20 month (range 4–39) follow up period. HBV DNA was detected by PCR in 1/22 donor serum, and in 11/21 liver grafts with normal histology. A mean of 12 months post-transplantation (range 1–23) HBV DNA was no longer detectable in graft biopsies from patients remaining HBsAg negative. Conclusion: Anti-HBs antibodies may control HBV replication in liver grafts from anti-HBc positive donors, without additional antiviral drugs. These grafts are thus suitable either to effectively vaccinated recipients or to those who are given HBIG to prevent HBV recurrence.

Roque-Afonso, A M; Feray, C; Samuel, D; Simoneau, D; Roche, B; Emile, J-F; Gigou, M; Shouval, D; Dussaix, E

2002-01-01

150

Clinical factors associated with a Candida albicans Germ Tube Antibody positive test in Intensive Care Unit patients  

PubMed Central

Background Poor outcomes of invasive candidiasis (IC) are associated with the difficulty in establishing the microbiological diagnosis at an early stage. New scores and laboratory tests have been developed in order to make an early therapeutic intervention in an attempt to reduce the high mortality associated with invasive fungal infections. Candida albicans IFA IgG has been recently commercialized for germ tube antibody detection (CAGTA). This test provides a rapid and simple diagnosis of IC (84.4% sensitivity and 94.7% specificity). The aim of this study is to identify the patients who could be benefited by the use of CAGTA test in critical care setting. Methods A prospective, cohort, observational multicentre study was carried out in six medical/surgical Intensive care units (ICU) of tertiary-care Spanish hospitals. Candida albicans Germ Tube Antibody test was performed twice a week if predetermined risk factors were present, and serologically demonstrated candidiasis was considered if the testing serum dilution was ? 1:160 in at least one sample and no other microbiological evidence of invasive candidiasis was found. Results Fifty-three critically ill non-neutropenic patients (37.7% post surgery) were included. Twenty-two patients (41.5%) had CAGTA-positive results, none of them with positive blood culture for Candida. Neither corrected colonization index nor antifungal treatment had influence on CAGTA results. This finding could corroborate that the CAGTA may be an important biomarker to distinguish between colonization and infection in these patients. The presence of acute renal failure at the beginning of the study was more frequent in CAGTA-negative patients. Previous surgery was statistically more frequent in CAGTA-positive patients. Conclusions This study identified previous surgery as the principal clinical factor associated with CAGTA-positive results and emphasises the utility of this promising technique, which was not influenced by high Candida colonization or antifungal treatment. Our results suggest that detection of CAGTA may be important for the diagnosis of invasive candidiasis in surgical patients admitted in ICU.

2011-01-01

151

Retargeting T Cells for HER2-Positive Tumor Killing by a Bispecific Fv-Fc Antibody  

PubMed Central

To exploit the biological and pharmacological properties of immunoglobulin constant domain Fc fragment and increase the killing efficacy of T cells, a single chain variable fragment specific to CD3 was fused with Fcab (Fc antigen binding), a mutant Fc fragment with specificity against Human epidermal growth factor receptor 2 (HER2) developed by F-star. The bispecific fusion named as FcabCD3 was expressed by transient transfection in HEK-293T cells and purified by affinity chromatography. Specific cytolytic activity of retargeted T cells to kill HER2 positive SKBR3 cell line was evaluated in vitro. FcabCD3 was able to retarget T cells to kill both Herceptin insensitive Colo205-luc cell line and HER2 low expression MDA-MB-231-luc cell line. Furthermore, FcabCD3 was effective in eliminating the Colo205 tumor established on BALB/c nu/nu mice.

Wang, Lei; He, Yanran; Zhang, Ge; Ma, Juan; Liu, Changzhen; He, Wen; Wang, Wei; Han, Huamin; Boruah, Bhargavi M.; Gao, Bin

2013-01-01

152

Retargeting T cells for HER2-positive tumor killing by a bispecific Fv-Fc antibody.  

PubMed

To exploit the biological and pharmacological properties of immunoglobulin constant domain Fc fragment and increase the killing efficacy of T cells, a single chain variable fragment specific to CD3 was fused with Fcab (Fc antigen binding), a mutant Fc fragment with specificity against Human epidermal growth factor receptor 2 (HER2) developed by F-star. The bispecific fusion named as FcabCD3 was expressed by transient transfection in HEK-293T cells and purified by affinity chromatography. Specific cytolytic activity of retargeted T cells to kill HER2 positive SKBR3 cell line was evaluated in vitro. FcabCD3 was able to retarget T cells to kill both Herceptin insensitive Colo205-luc cell line and HER2 low expression MDA-MB-231-luc cell line. Furthermore, FcabCD3 was effective in eliminating the Colo205 tumor established on BALB/c nu/nu mice. PMID:24086580

Wang, Lei; He, Yanran; Zhang, Ge; Ma, Juan; Liu, Changzhen; He, Wen; Wang, Wei; Han, Huamin; Boruah, Bhargavi M; Gao, Bin

2013-01-01

153

[Anti-deamidated gliadin peptides antibodies and coeliac disease: state of art and analysis of false-positive results from five assays].  

PubMed

Recently, anti-deamidated gliadin antibodies were proposed for the serological diagnosis of celiac disease. We evaluate the specificity of different anti-deamidated gliadin antibodies ELISA in comparison with conventional anti-native gliadin kits. Serum samples from 46 non celiac patients were analyzed by five different quantitative ELISA for anti-native gliadin, anti-deamidated gliadin and anti-transglutaminase neo-epitope antibodies together with a screening ELISA. Twenty-four percent of the patients demonstrated anti-native gliadin IgA and 63% IgG antibodies. Using anti-deamidated gliadin antibodies, the number of false positive IgA and, particularly, IgG results, markedly decreased in the non celiac patients: 21 and 24% respectively with anti-Gliadin (GAF-3X) Euroimmun kit, 7 and 26% with Bindazyme Human Anti-Gliadin (MGP) The Binding Site kit and 0 and 41% with Celiac G+ Immco kit. The new assay which makes use of the physiological complex of tissue transglutaminase cross-linked with deamidated gliadin peptides, called neo-epitope, did not improve the differential diagnosis of celiac disease with 30% of false positive results in IgG (2% in IgA). Using the Inova screening kit, a positive result for IgA and/or IgG anti-deamidated gliadin and/or anti-tissue transglutaminase antibodies was obtained in 24% of the non celiac patients. In conclusion, our study assessed the superiority, in terms of specificity, of anti-deamidated gliadin antibodies, over the conventional anti-gliadin antibodies for the differential diagnosis of celiac disease. PMID:20348047

Lutteri, Laurence; Sagot, Clémence; Chapelle, Jean-Paul

2010-01-01

154

Elaboration of stable and antibody functionalized positively charged colloids by polyelectrolyte complexation between chitosan and hyaluronic acid.  

PubMed

In this study, we describe the elaboration of multifunctional positively charged polyelectrolyte complex (PEC) nanoparticles, designed to be stable at physiological salt concentration and pH, for effective targeted delivery. These nanoparticles were obtained by charge neutralization between chitosan (CS) as polycation and hyaluronic acid (HA) as polyanion. We showed that the course of the complexation process and the physico-chemical properties of the resulting colloids were impacted by (i) internal parameters such as the Degree of Acetylation (DA, i.e., the molar ration of acetyl glucosamine residues) and molar mass of CS, the HA molar mass and (ii) external parameters like the charge mixing ratio and the polymer concentrations. As a result, nonstoichiometric colloidal PECs were obtained in water or PBS (pH 7.4) and remained stable over one month. The polymer interactions were characterized by thermal analysis (DSC and TGA) and the morphology was studied by scanning electron microscopy. A model antibody, anti-ovalbumine (OVA) immunoglobulin A (IgA) was sorbed on the particle surface in water and PBS quantitatively in 4 h. The CS-HA/IgA nanoparticles average size was between 425-665 nm with a positive zeta potential. These results pointed out that CS-HA can be effective carriers for use in targeted drug delivery. PMID:23877050

Polexe, Ramona C; Delair, Thierry

2013-01-01

155

Antinuclear Antibody Profile in UCD Line 200 Chickens: A Model for Progressive Systemic Sclerosis  

Microsoft Academic Search

The fully blown disease of human progressive systemic sclerosis (PSS, scleroderma) is serologically associated with the emergence of several types of autoantibodies, some of them regarded as more specific for scleroderma (e.g. Scl-70, anti-centromere) and some common also to other connective tissue diseases (e.g. anti-ssDNA). Since most patients suffering from PSS are not under medical control until clinical manifestations are

Matthias S. Gruschwitz; Yehuda Shoenfeld; Margalit Krupp; Eric Gershwin; Eduard Penner; Hans-Peter Brezinschek; Georg Wick

1993-01-01

156

False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies  

PubMed Central

Anti-myeloperoxidase antibodies (anti-MPO) are a major type of anti-neutrophil cytoplasmic antibody (ANCA). While evaluating anti-MPO monoclonal antibodies from SCG/Kj mice, we observed several hybridomas that appeared to react with both MPO and DNA. Sera from some patients with systemic lupus erythematosus (SLE) also react with MPO and DNA. We hypothesized that the MPO binding activity is a false-positive result due to the binding of DNA, contained within the antigen binding site of anti-DNA antibodies, to the cationic MPO. Antibodies from tissue culture supernatants from ‘dual reactive’ hybridomas were purified under high-salt conditions (3 m NaCl) to remove any antigen bound to antibody. The MPO and DNA binding activity were measured by ELISA. The MPO binding activity was completely abrogated while the DNA binding activity remained. The MPO binding activity was restored, in a dose-dependent manner, by the addition of increasing amount of calf-thymus DNA (CT-DNA) to the purified antibody. Sera from six patients with SLE that reacted with both MPO and DNA were treated with DNase and showed a decrease in MPO binding activity compared with untreated samples. MPO binding activity was observed when CT-DNA was added to sera from SLE patients that initially reacted with DNA but not with MPO. These results suggest that the DNA contained within the antigen binding site of anti-DNA antibodies could bind to the highly cationic MPO used as substrate antigen in immunoassays, resulting in a false-positive test.

Jethwa, H S; Nachman, P H; Falk, R J; Jennette, J C

2000-01-01

157

Specificity of antibodies to O-acetyl-positive and O-acetyl-negative group C meningococcal polysaccharides in sera from vaccinees and carriers.  

PubMed Central

Most group C Neisseria meningitidis strains produce an O-acetyl-positive polysaccharide, a homopolymer of alpha-2----9-linked N-acetylneuraminic acid with O-acetyl groups at the C-7 and C-8 of its sialic acid residues. The majority of disease isolates have been reported to contain this polysaccharide. Some strains produce group C polysaccharide lacking O-acetyl groups. The licensed vaccine contains the O-acetyl-positive polysaccharide. We have measured the antibody specificities to the two polysaccharides in sera from asymptomatic group C meningococcal carriers and vaccinated adults by a new enzyme-linked immunosorbent assay (ELISA) procedure using methylated human serum albumin for coating the group C polysaccharide onto microtiter plates. Inhibition of binding of serum antibodies to polysaccharide-coated plates was measured by ELISA after incubation with O-acetyl-positive and O-acetyl-negative group C polysaccharides. Greater inhibition of binding of carrier sera was observed with the homologous polysaccharide. There was substantial inhibition of binding of vaccinee sera to the O-acetyl-positive polysaccharide-coated plate following preincubation with O-acetyl-positive polysaccharide, but homologous inhibition on plates coated with the O-acetyl-negative polysaccharide required much higher concentrations of polysaccharide. Carrier sera may have a higher proportion of antibodies with greater specificity for the O-acetyl-negative polysaccharide, while vaccinee sera contain antibodies with greater affinity for the O-acetyl-positive polysaccharide. Studies with monoclonal antibodies specific for O-acetyl-positive and O-acetyl-negative polysaccharides reveal that the percentage of group C meningococcal disease caused by O-acetyl-negative strains remains about 15%, as found over 15 years ago.

Arakere, G; Frasch, C E

1991-01-01

158

Reduced intestinal colonisation with F18-positive enterotoxigenic Escherichia coli in weaned pigs fed chicken egg antibody against the fimbriae  

Microsoft Academic Search

Newly weaned pigs were fed a basal diet containing either egg antibody against fimbriae F18 at a high or low level, control egg powder or no egg, and challenged with enterotoxigenic Escherichia coli with fimbriae F18. The challenge was repeated after termination of the antibody treatment. Antibody-containing egg powder was produced by vaccination of hens with semi-purified fimbriae of the

Armando Zúñiga; Hideaki Yokoyama; Pia Albicker-Rippinger; Ernst Eggenberger; Hans Ulrich Bertschinger

1997-01-01

159

Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report  

PubMed Central

Introduction Anti-neutrophil cytoplasmic antibody-associated vasculitis has been associated with many drugs and it is a relatively rare side effect of the antihypertensive drug hydralazine. The diagnosis and management of patients who have anti-neutrophil cytoplasmic antibody-associated vasculitis may be challenging because of its relative infrequency, variability of clinical expression and changing nomenclature. The spectrum of anti-neutrophil cytoplasmic antibody-associated vasculitis is wide and can be fatal. This case documents a 62-year-old woman who presented with hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis with a puzzling cutaneous rash. Case presentation We report a rare case of hydralazine-induced anti-neutrophil cytoplasmic antibody-associated vasculitis in a 62-year-old Caucasian woman who presented with a vasculitic syndrome with a sore throat, mouth ulcers and otalgia after several months of constitutional symptoms. She then proceeded to develop a rash over her right lower limb. Clinically, the rash had features to suggest Sweet’s syndrome, but also had some appearances consistent with embolic phenomena and did not have the appearance of palpable purpure usually associated with cutaneous vasculitis. Differential diagnoses were hydralazine-associated Sweet’s syndrome, streptococcal-induced cutaneous eruption or an unrelated contact dermatitis. A midstream urine sample detected glomerular blood cells in the setting of anti-neutrophil cytoplasmic antibody-positive renal vasculitis and Streptococcus pyogenes bacteremia. A renal biopsy revealed a pauci-immune, focally necrotizing glomerulonephritis with small crescents. Her skin biopsy revealed a heavy neutrophil infiltrate involving the full thickness of the dermis with no evidence of a leucocytoclastic vasculitis, but was non-specific. She was initially commenced on intravenous lincomycin for her bloodstream infection and subsequently commenced on immunosuppression after cessation of hydralazine. The patient was subsequently discharged from hospital after a rapid clinical improvement. Conclusion Hydralazine-induced anti-neutrophil cytoplasmic antibody-positive renal vasculitis is a rare adverse effect and can present with a severe vasculitic syndrome with multiple organ involvement. Features of this association include the presence of high titres of anti-myeloperoxidase-anti-neutrophil cytoplasmic antibody with multi-antigenicity, positive anti-histone antibodies and the lack of immunoglobulin and complement deposition histopathogically. A rash that is characteristic of Sweet’s syndrome has also been described as an association. Prompt cessation of hydralazine may be sufficient to reverse disease activity but immunosuppression may be needed for definite treatment.

2013-01-01

160

Development and evaluation of a flow cytometry microsphere assay to detect anti-histone antibody in dogs  

Microsoft Academic Search

Anti-nuclear antibody (ANA) is one of the diagnostic parameters that support a diagnosis of autoimmune disorders in humans, dogs, and horses, particularly the condition systemic lupus erythematosus (SLE). The most commonly used method for detecting ANA in canine serum is the indirect immunofluorescence antibody assay (IFA) that detects dog IgG with reactivity towards mammalian cell nuclei. Interpretation of the IFA

Shoma Paul; Melinda J. Wilkerson; Wilma Shuman; Kenneth R. Harkin

2005-01-01

161

Lamivudine compared with newer antivirals for prophylaxis of hepatitis B core antibody positive livers: a cost-effectiveness analysis.  

PubMed

There is concern over the development of de novo hepatitis B in patients receiving liver transplants from hepatitis B surface antigen negative, hepatitis B core antibody positive donors. Current practice is to place such patients on indefinite lamivudine prophylaxis; however, there is a small risk of breakthrough infection and newer antivirals for hepatitis B are available. The objective of this study was to determine the cost-effectiveness of lamivudine compared with the newer agents, tenofovir and entecavir, in the prophylaxis setting using a Markov model. Three strategies were examined which consisted of either lamivudine or entecavir monoprophylaxis with tenofovir add-on therapy after breakthrough or tenofovir monoprophylaxis with emtricitabine add-on therapy after breakthrough. In the base case scenario, lamivudine was the most cost-effective option at a threshold of $100?000 per quality-adjusted life-year and this remained robust despite parameter uncertainty. Tenofovir had an incremental cost-effectiveness ratio of $3?540?194.77 while other strategies were superior to entecavir therapy. Until drug costs decrease, lamivudine remains the most cost-effective option for hepatitis B prophylaxis in the liver transplant setting. PMID:24460820

Wright, A J; Fishman, J A; Chung, R T

2014-03-01

162

[A case of anti-Hu antibody- and anti-GluR epsilon2 antibody-positive paraneoplastic neurological syndrome presenting with limbic encephalitis and peripheral neuropathy].  

PubMed

We report a case of paraneoplastic neurological syndrome with anti-neuronal antibodies, namely anti-Hu and anti-GluR epsilon 2 antibodies in sera. A 72-year-old male had a transient history of eye movement disorder and sensory neuropathy, which improved spontaneously. Two years later, he was admitted to another hospital because of gait disturbance, numbness of the hands and an attack of unconsciousness with generalized convulsion. He was admitted to our hospital with prolonged consciousness disturbance and muscular weakness of all extremities. On admission his consciousness deteriorated slightly without neck stiffness. His cranial nervous system was normal except for incomplete abduction and elevation of both eyes. The patient had severe distal dominant weakness and atrophy in the muscles of all four limbs. Muscle tonus was decreased and hyporeflexia was noted in the four extremities. Plantar response was extensor. Neither sensory disturbance nor ataxia was observed. Cranial MRI showed T2-weighted high intensity lesions in the bilateral mesial temporal lobes, including the hippocampi. A nerve conduction study revealed motor-dominant peripheral neuropathy with prolonged latency; the amplitudes of compound muscle action potentials were severely reduced in all four limbs and those of sensory nerve action potentials were moderately reduced in the right upper and lower extremities. We also found a left hilar lymphadenopathy showing accumulation of FDG on PET, suggesting a possibility of malignancy. Anti-Hu and anti-GluR epsilon 2 antibodies were detected in sera but not in CSF. We diagnosed him with limbic encephalitis and peripheral neuropathy due to paraneoplastic neurological syndrome and treated him with two courses of intravenous immunoglobulin (IVIg) (400 mg/kg, 5 days). The consciousness disturbance, and prolonged distal latency revealed by motor nerve conduction studies improved slightly. Although the roles of anti-neuronal antibodies in paraneoplastic conditions remain unknown, we consider that IVIg may be worth using to treat cases with anti-Hu and anti-GluR epsilon 2 antibodies. PMID:20681263

Samejima, Shoko; Tateishi, Takahisa; Arahata, Hajime; Shigeto, Hiroshi; Ohyagi, Yasumasa; Kira, Jun-ichi

2010-07-01

163

Amphibole, but not chrysotile, asbestos induces anti-nuclear autoantibodies and IL-17 in C57BL/6 mice.  

PubMed

Abstract Exposure to amphibole asbestos has been associated with production of autoantibodies in mice and humans, and increases the risk of systemic autoimmune disease. However, epidemiological studies of chrysotile exposure have not indicated a similar induction of autoimmune responses. To demonstrate this difference in controlled exposures in mice, and to explore possible mechanistic explanations for the difference, C57BL/6 mice were exposed intratracheally to amphibole or chrysotile asbestos, or to saline only. Serum antinuclear antibodies (ANA), antibodies to extractable nuclear antigens (ENA), serum cytokines, and immunoglobulin isotypes were evaluated 8 months after the final treatment. The percentages of lymphocyte sub-sets were determined in the spleen and lungs. The results show that amphibole, but not chrysotile, asbestos increases the frequency of ANA/ENA in mice. Amphibole and chrysotile both increased multiple serum cytokines, but only amphibole increased IL-17. Both fibers decreased IgG1, without significant changes in other immunoglobulin isotypes. Although there were no gross changes in overall percentages of T- and B-cells in the spleen or lung, there was a significant increase in the normally rare populations of suppressor B-cells (CD19(+), CD5(+), CD1d(+)) in both the spleen and lungs of chrysotile-exposed mice. Overall, the results suggest that, while there may be an inflammatory response to both forms of asbestos, there is an autoimmune response in only the amphibole-exposed, but not the chrysotile-exposed mice. These data have critical implications in terms of screening and health outcomes of asbestos-exposed populations. PMID:24164284

Ferro, Aaron; Zebedeo, Christian Nash; Davis, Chad; Ng, Kok Whei; Pfau, Jean C

2014-07-01

164

Intestinal titres of anti-tissue transglutaminase 2 antibodies correlate positively with mucosal damage degree and inversely with gluten-free diet duration in coeliac disease.  

PubMed

It has always been known that anti-tissue transglutaminase 2 (anti-TG2) antibodies are produced in the small intestine. Their serum titres correlate with mucosal damage degree and decrease on a gluten-free diet (GFD). We aimed to correlate intestinal anti-TG2 antibodies levels with degree of mucosal damage and GFD duration. Thirty-four active, 71 potential and 24 CD patients on GFD for at least 2 years were enrolled. Anti-TG2 deposits were detected in intestinal biopsies by double immunofluorescence. Biopsies were cultured for 24?h with medium, and with gliadin peptic tryptic digest (PTG) or A-gliadin peptide 31-43 (P31-43). Anti-TG2 antibodies secreted into supernatants were measured by enzyme-linked immunosorbent assay (ELISA). All active CD patients secreted high titres of anti-TG2 antibodies into culture medium that increased with the worsening of mucosal injury (Spearman's r?=?0·71; P?antibodies into supernatants, eight of nine negative treated patients being on GFD for more than 10 years. An inverse correlation between antibody titres and duration of GFD was found, (Spearman's r?=?-0·52; P?positive treated CD patients had been on GFD for fewer than 6 years and were also positive for secreted anti-TG2. In treated patients, PTG/P31-43 was not able to induce secretion of anti-TG2 antibodies into culture medium. Measurement of anti-TG2 antibodies in biopsy supernatants proved to be more sensitive than detection by immunofluorescence to reveal their intestinal production. Intestinal antiTG2 antibodies titres correlated positively with the degree of mucosal damage and inversely with the duration of GFD. PMID:24773630

Tosco, A; Auricchio, R; Aitoro, R; Ponticelli, D; Primario, M; Miele, E; Rotondi Aufiero, V; Discepolo, V; Greco, L; Troncone, R; Maglio, M

2014-09-01

165

The value of ultrasonography in predicting arthritis in auto-antibody positive arthralgia patients: a prospective cohort study  

PubMed Central

Introduction Ultrasonography (US) has better sensitivity than clinical evaluation for the detection of synovitis in early rheumatoid arthritis (RA). Patients presenting with arthralgia and a positive anti-citrullinated protein antibodies (ACPA) and/or Rheumatoid Factor (IgM-RF) status are at risk for developing RA. In the present study, US utility and predictive properties in arthralgia patients at risk for the development of arthritis were studied. Methods 192 arthralgia patients with ACPA and/or IgM-RF were included. Absence of clinical arthritis was confirmed by two physicians. US was performed by one of two trained radiologists of any painful joint, and of adjacent and contralateral joints. Joint effusion, synovitis and power Doppler (PD) signal in the synovial membrane of the joints and tenosynovitis adjacent to the joint were evaluated and classified on a 4-grade semi-quantitative scale. Grade 2-3 joint effusion, synovitis, tenosynovitis and grade 1-3 Power Doppler signal were classified as abnormal. Results Forty-five patients (23%) developed arthritis after a mean of 11 months. Inter-observer reliability for synovitis and PD was moderate (kappa 0.46, and 0.56, respectively) and for joint effusion low (kappa 0.23). The prevalence of tenosynovitis was too low to calculate representative kappa values. At joint level, a significant association was found between US abnormalities and arthritis development in that joint for joint effusion, synovitis and PD. At patient level, a trend was seen towards more arthritis development in patients who had US abnormalities for joint effusion, synovitis, PD and tenosynovitis. Conclusions US abnormalities were associated with arthritis development at joint level, although this association did not reach statistical significance at patient level. US could potentially be used as a diagnostic tool for subclinical arthritis in seropositive arthralgia patients. However, further research is necessary to improve test characteristics.

2010-01-01

166

Defining a social problem: socio-historical analysis of the antinuclear weapons movement  

SciTech Connect

This dissertation is a socio-historical analysis of the anti-nuclear weapons movement in the United States. This work conceptualizes social movements in advanced industrial societies by synthesizing certain aspects of social constructionism, resource mobilization, and new class theory. The research design is a socio-historical, comparative case study. Both qualitative and quantitative methods are employed for data analysis. Extensive content analysis of documents and interviews with key actors are supplemented with a critical analysis of a wide variety of primary and secondary data. All major antinuclear weapons protest, particularly the Atomic Scientists Movement of the 1940s, the Ban-the-Bomb Movement of the 1950s and 1960s, and the Freeze Movement of the 1980s, shared similar characteristics, and experienced similar problems. The findings are congruent with the theoretical synthesis. Antinuclear weapons protest is best understood as a new class phenomenon, in which intellectuals have mobilized resources to challenge the ruling elite. Yet, though the protest has succeeded in challenging the legitimacy of the ruling apparatus, successes of the movement have been mostly symbolic.

McCrea, F.B.

1988-01-01

167

Prevalence and clinical significance of antikeratin antibodies and other serological markers in Lithuanian patients with rheumatoid arthritis  

PubMed Central

OBJECTIVES—To assess the clinical value of several serological markers in Lithuanian patients with rheumatoid arthritis (RA) compared with control patients with rheumatic disease and age matched healthy controls.?METHODS—Serum samples from 96 patients with RA of approximately 8 years' duration, 90 rheumatic disease controls, and 37 healthy subjects were tested. Antikeratin antibody (AKA), antineutrophil cytoplasmic antibody (ANCA), and antinuclear antibody (ANA) titres were estimated by indirect immunofluorescence (IIF) and serum samples positive for ANA and ANCA were further studied by enzyme linked immunosorbent assay (ELISA). IgA and IgM rheumatoid factors (RF) were measured by ELISA.?RESULTS—A positive AKA test was highly specific for RA (diagnostic specificity 97%), being found in 44% of the patients. Although both RF tests had a higher sensitivity, they were less specific for RA. ANCA was detected in 33% of patients with RA but lacked diagnostic specificity. AKA and ANCA were associated with more erosive disease and the presence of extra-articular manifestations. Positivity for AKA, IgA RF, and ANCA was significantly associated with disease activity and worse functional capacity. However, in multiple regression analysis only positivity for AKA was significantly correlated with functional disability (p=0.0001), evaluated by the Steinbrocker functional classification, and no single marker had any relation with radiological damage.?CONCLUSION—Although AKA showed the highest disease specificity, all serological markers studied except ANA exhibited interesting associations with important clinical and paraclinical parameters of RA.??

Vasiliauskiene, L; Wiik, A; Hoier-Madsen, M

2001-01-01

168

Increased Detection of Sin Nombre Hantavirus RNA in Antibody-Positive Deer Mice from Montana, USA: Evidence of Male Bias in RNA Viremia  

PubMed Central

Hantaviruses are widespread emergent zoonotic agents that cause unapparent or limited disease in their rodent hosts, yet cause acute, often fatal pulmonary or renal infections in humans. Previous laboratory experiments with rodent reservoir hosts indicate that hantaviruses can be cleared from host blood early in the infection cycle, while sequestered long term in various host organs. Field studies of North American deer mice (Peromyscus maniculatus), the natural reservoir of Sin Nombre hantavirus, have shown that viral RNA can be transiently detected well past the early acute infection stage, but only in the minority of infected mice. Here, using a non-degenerate RT-PCR assay optimized for SNV strains known to circulate in Montana, USA, we show that viral RNA can be repeatedly detected on a monthly basis in up to 75% of antibody positive deer mice for periods up to 3–6 months. More importantly, our data show that antibody positive male deer mice are more than twice as likely to have detectable SNV RNA in their blood as antibody positive females, suggesting that SNV-infected male deer mice are more likely to shed virus and for longer periods of time.

Bagamian, Karoun H.; Towner, Jonathan S.; Mills, James N.; Kuenzi, Amy J.

2013-01-01

169

A case of anti-GA1 antibody-positive Fisher syndrome with elevated tau protein in cerebrospinal fluid.  

PubMed

We describe a boy with Fisher syndrome. He presented the typical symptoms of Fisher syndrome, including external ophthalmoplegia, abnormality of convergence, and areflexia, after an episode of Campylobacter enterocolitis. Atypically, however, anti-GA1 antibody was detected in his serum, though anti-GQ1b and anti-GT1a antibodies were not. In addition, the tau protein level in his cerebrospinal fluid was elevated. Generally, Fisher syndrome is a self-limiting disease and has a good prognosis. In our patient, however, mild diplopia and areflexia persisted 6 months after their onset. Here, we report on the first Fisher syndrome patient with anti-GA1 antibody in the serum and elevated tau protein in the cerebrospinal fluid. PMID:21742448

Oyazato, Yoshinobu; Shiihara, Takashi; Kusunoki, Susumu; Adachi, Masao; Ohnishi, Noriko; Taniguchi, Hiroaki; Nishiyama, Atsushi; Watanabe, Aika; Kobayashi, Mitsuro; Kamioka, Ichiro

2012-04-01

170

HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma).  

PubMed Central

OBJECTIVE--To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). METHODS--HLA class II genes were determined using polymerase chain reaction/restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. RESULTS--Frequency of DQB1*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA with a polar amino acid at position 26 in the DQB1 beta 1 domain, which was demonstrated in white North Americans, was not observed in Japanese. The DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas DRB1*1502 was associated with low ACA titres and a low frequency of centromere protein C (CENP-C) reactivity. CONCLUSIONS--These results suggest that the ACA response is associated with multiple HLA class II genes and that ACA positive SSc patients are heterogeneous in terms of immunogenetic background.

Kuwana, M; Okano, Y; Kaburaki, J; Inoko, H

1995-01-01

171

Myeloperoxidase-antineutrophil cytoplasmic antibody-positive crescentic glomerulonephritis complicating the course of Graves' disease: Report of three adult cases  

Microsoft Academic Search

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis has been recently recognized in Graves' disease patients treated with propylthiouracil. We have experienced three adult cases of Graves' disease with main features being renal derangements. All three patients, who were between the ages of 22 and 82 years, had been treated with propylthiouracil for 2 to 5 years after a diagnosis of Graves' disease.

Masayuki Tanemoto; Hiroshi Miyakawa; Junichi Hanai; Masako Yago; Masafumi Kitaoka; Shunya Uchida

1995-01-01

172

Differences in synovial fluid cytokine levels but not in synovial tissue cell infiltrate between anti-citrullinated peptide/protein antibody-positive and -negative rheumatoid arthritis patients  

PubMed Central

Introduction Comparative data on synovial cell infiltrate and cytokine levels in anti citrullinated peptide/protein antibody (ACPA)-positive and ACPA negative rheumatoid arthritis (RA) patients are scarce. Our aim was to analyze synovial cell infiltrate and synovial fluid (SF) levels of cytokines in patients with RA according to the presence or absence of ACPA in serum. Methods A cross-sectional study in a single center including consecutive RA patients was performed. Patients were defined as 'ACPA negative' if serum was negative to two different ACPAs [second generation commercial anti-cyclic citrullinated peptide antibodies (CCP2) and chimeric fibrin/filaggrin citrullinated antibodies]. Parallel synovial tissue (ST) biopsies and SF were obtained by knee arthroscopy. Synovial cell infiltrate and endothelial cells were analyzed by immunohistochemistry and SF levels of Th1, Th2, Th17 and pro-inflammatory cytokines by Quantibody(R) Human Array. Results A total of 83 patients underwent arthroscopy, with a mean age of 55.9?±?12 years, and mean disease duration of 45 months (interquartile range, IQR 10.8 to 122). 62% were female and 77% were ACPA positive. No significant differences were found in clinical variables, acute phase reactants, synovial cell infiltrate or lymphoid neogenesis (LN) between ACPA positive and negative patients. However ACPA positive patients had significantly higher levels of IL-1?, IL-10, IL-17 F and CC chemokine ligand 20 (CCL-20) than ACPA negative patients. Conclusions In our cohort of patients with RA no significant differences were found in synovial cell infiltrate or synovial LN according to ACPA status. However, ACPA positive patients had higher levels of T-cell derived and pro-inflammatory cytokines than ACPA negative patients. As systemic and local inflammation was similar in the two groups, these findings support a distinct synovial physiopathology.

2013-01-01

173

Limited reliability of the indirect immunofluorescence technique for the detection of anti-Rib-P antibodies  

PubMed Central

Introduction Autoantibodies to the ribosomal P proteins represent a highly specific marker for the diagnosis of systemic lupus erythematosus, where they have been associated with certain clinical manifestations. Historically, autoantibodies against ribosomal P proteins have been detected by indirect immunofluorescence, immunodiffusion, immunoblot, and other immunoassays. More recently, enzyme-linked immunosorbent assays and line and addressable laser bead immunoassays have become more widely used. The primary goal of this study was to determine the sensitivity of indirect immunofluorescence using conventional HEp-2 substrates in the detection of sera with ribosomal P antibodies as detected by other immunoassays. Methods Anti-ribosomal P-positive sera (n = 345) as detected by an addressable laser bead immunoassay were collected between 2003 and 2007 and analysed by indirect immunofluorescence. Furthermore, 51 anti-ribosomal P-positive samples from an unselected systemic lupus erythematosus cohort (n = 100) and the Centers for Disease Control and Prevention (CDC) anti-nuclear antibody (ANA) reference sera were tested for anti-ribosomal P reactivity. Results In the cohort of 345 anti-ribosomal P-positive samples identified by addressable laser bead immunoassay, a low sensitivity (<30%) of indirect immunofluorescence on HEp-2 cell substrates was observed. Although the degree of sensitivity varied among different manufacturers, all immunofluorescence substrates exhibited limited sensitivity and false-negative results were not restricted to samples with low anti-ribosomal P titers. Even the anti-ribosomal P reactivity of CDC ANA reference serum number 12 was not clearly predictable by indirect immunofluorescence. Comparison of five different methods for the detection of anti-ribosomal P found moderate qualitative agreements. Conclusions Based on our data, we conclude that indirect immunofluorescence on HEp-2 cells is not a reliable screening test for the prediction of ribosomal P antibodies. As this method is widely used as a first-line screening test for anti-nuclear and other autoantibodies, special considerations for the detection of ribosomal P antibodies are needed. As with many other autoantibodies, further effort is required for the standardisation of ribosomal P immunoassays.

Mahler, Michael; Ngo, Jennifer T; Schulte-Pelkum, Johannes; Luettich, Tanja; Fritzler, Marvin J

2008-01-01

174

Forced usage of positively charged amino acids in immunoglobulin CDR-H3 impairs B cell development and antibody production  

PubMed Central

Tyrosine and glycine constitute 40% of complementarity determining region 3 of the immunoglobulin heavy chain (CDR-H3), the center of the classic antigen-binding site. To assess the role of DH RF1-encoded tyrosine and glycine in regulating CDR-H3 content and potentially influencing B cell function, we created mice limited to a single DH encoding asparagine, histidine, and arginines in RF1. Tyrosine and glycine content in CDR-H3 was halved. Bone marrow and spleen mature B cell and peritoneal cavity B-1 cell numbers were also halved, whereas marginal zone B cell numbers increased. Serum immunoglobulin G subclass levels and antibody titers to T-dependent and T-independent antigens all declined. Thus, violation of the conserved preference for tyrosine and glycine in DH RF1 alters CDR-H3 content and impairs B cell development and antibody production.

Ippolito, Gregory C.; Schelonka, Robert L.; Zemlin, Michael; Ivanov, Ivaylo I.; Kobayashi, Ryoki; Zemlin, Cosima; Gartland, G. Larry; Nitschke, Lars; Pelkonen, Jukka; Fujihashi, Kohtaro; Rajewsky, Klaus; Schroeder, Harry W.

2006-01-01

175

Molecular Targeting andTreatment of Composite EGFR and EGFRvIII- Positive Gliomas Using Boronated Monoclonal Antibodies  

Microsoft Academic Search

Purpose: The purpose of the present study was to evaluate the anti ^ epidermal growth factor receptor (EGFR) monoclonal antibody (mAb), cetuximab, (IMC-C225) and the anti-EGFRvIII mAb, L8A4, used in combination as delivery agents for boron neutron capture therapy (BNCT) of a rat glioma composed of a mixture of cells expressing either wild-type (F98EGFR )o r mutant receptors(F98npEGFRvIII). Experimental Design:

Weilian Yang; Gong Wu; Rolf F. Barth; Michele R. Swindall; Achintya K. Bandyopadhyaya; Werner Tjarks; Kevin Tordoff; Melvin Moeschberger; Thomas J. Sferra; Kent J. Riley; Michael J. Ciesielski; Robert A. Fenstermaker; Carol J. Wikstrand

2008-01-01

176

Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis  

PubMed Central

Background: Antibodies against cyclic citrullinated peptide (anti-CCP) are considered to be specific for rheumatoid arthritis (RA). Objective: To assess the clinical significance of anti-CCP in a cohort of patients with juvenile idiopathic arthritis (JIA). Methods: Anti-CCP were tested by an enzyme linked immunosorbent assay (ELISA) in serum samples from 109 patients with JIA (30 boys, 79 girls), with a mean age of 8.7 years (range 0.6–20.3) and mean disease duration of 3.6 years (range 3 months to 15.6 years). As control groups, anti-CCP were also tested in sera of 30 healthy children, 25 patients with juvenile onset systemic lupus erythematosus (SLE), and 50 adult patients (30 with RA, 20 with SLE). Results: Positive anti-CCP values were found in sera of two patients with JIA (2%), one with polyarthritis, and one with oligoarthritis. Statistical analysis showed that anti-CCP were not associated with the presence of antinuclear antibodies, raised erythrocyte sedimentation rate, or erosions. In the control groups, none of the patients with juvenile onset SLE and only one of 20 adults with SLE were positive for anti-CCP, but 19/30 (63%) adults with RA showed anti-CCP positivity. Conclusions: Anti-CCP can be detected in children with JIA, but are less frequently present than in adults with RA.

Avcin, T; Cimaz, R; Falcini, F; Zulian, F; Martini, G; Simonini, G; Porenta-Besic, V; Cecchini, G; Borghi, M; Meroni, P

2002-01-01

177

Thyroid Antibodies, Autoimmunity and Cognitive Decline: Is There a Population-Based Link?  

PubMed Central

Background Autoimmunity is considered an uncommon but under-recognised cause of cognitive decline. Methods Serum samples from 3,253 randomly selected subjects enrolled in the Hunter Community Study, aged 55-85 years, were assayed for thyrotropin stimulatory hormone, anti-thyroid peroxidase antibodies (TPO-Ab), anti-nuclear antibodies (ANA) and extractable nuclear antigens (ENA). Cognitive function was assessed using the Audio Recorded Cognitive Screen (ARCS) tool. Results TPO-Ab were found in 8.4% and ANA in 27.9% of the study population, of whom 3% had positive ENA findings. No relationship was found between the ARCS score and either TPO-Ab (coefficient = 0.133; 95% CI ?0.20, 0.82, p = 0.616), ANA at a low (coefficient = 1.01; 95% CI ?2.58, 0.55, p = 0.203) or a high titre (coefficient = ?0.65; 95% CI ?2.59, 1.28, p = 0.508), or ENA antibodies (coefficient = 5.12; 95% CI ?0.53, 10.77; p = 0.076). Conclusions Autoantibody findings are common in an aging population and are not associated with cognitive decline.

Napthali, Kate; Boyle, Michael; Tran, Huy; Schofield, Peter W.; Peel, Roseanne; McEvoy, Mark; Oldmeadow, Christopher; Attia, John

2014-01-01

178

Antibody-penicillin-V-amidase conjugates kill antigen-positive tumor cells when combined with doxorubicin phenoxyacetamide  

Microsoft Academic Search

Summary The two monoclonal antibodies (mAb), L6 (anti-carcinoma), and 1F5 [anti-(B-cell-lymphoma)], were chemically linked to the enzyme penicillin-V amidase (PVA), which hydrolyzes phenoxyacetamides, to explore the potential of using mAb-enzyme conjugates for the localizaton of chemotherapeutic drugs at tumor cells. The phenoxyacetamide derivatives of doxorubicin and melphalan were prepared, yielding the less toxic amides, doxorubicin-N-p-hydroxyphenoxyacetamide (DPO) and melphalan-N-p-hydroxyphenoxyacetamide (MelPO). These

David E. Kerrl; Peter D. Senter; William V. Burnett; David L. Hirschberg; Ingegerd Hellströml; Karl Erik Hellström

1990-01-01

179

Schistosome Infection Intensity Is Inversely Related to Auto-Reactive Antibody Levels  

Microsoft Academic Search

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)

Francisca Mutapi; Natsuko Imai; Norman Nausch; Claire D. Bourke; Nadine Rujeni; Kate M. Mitchell; Nicholas Midzi; Mark E. J. Woolhouse; Rick M. Maizels; Takafira Mduluza

2011-01-01

180

Different amounts of protein-bound citrulline and homocitrulline in foot joint tissues of a patient with anti-citrullinated protein antibody positive erosive rheumatoid arthritis  

PubMed Central

Background Antibodies binding to citrullinated proteins are a frequent finding in rheumatoid arthritis patients and may precede the onset of clinical symptoms several years. The antibodies are a predisposing factor for bone erosions but their origin is unknown. In this study we analyze in detail the levels of protein bound citrulline and homocitrulline in several tissue samples of a single erosive arthritic surgery patient. Methods Serum antibodies binding to CCP, MCV and citrulline- or homocitrulline-containing type I and II collagen carboxytelopeptides were measured. Tissue samples of a single RA patient, taken in two separate operations performed with two-year time span were hydrolyzed and analyzed for citrulline and homocitrulline content by HPLC. Results Protein-bound citrulline and homocitrulline were found in several joint tissues of a RA patient with ACPA-positive erosive disease. The amount of homocitrulline stayed relatively constant between the different tissues. The amount of citrulline in erosive tissue was 3-times higher than in non-erosive tissue in the first operation. In the samples of the second operation 3-4-times higher mean amounts of citrulline were found in two out of the six tissues investigated. Conclusions Homocitrulline is present in rheumatoid nodule together with citrulline. There is more variation in the amount of citrulline than in the amount of homocitrulline between the tissues. The tissue sample containing the most citrulline was the most erosive.

2013-01-01

181

Immune responses induced by DNA vaccines encoding Newcastle virus haemagglutinin and/or fusion proteins in maternal antibody-positive commercial broiler chicken.  

PubMed

1. The immune responses induced by recombinant plasmids containing Newcastle disease virus (NDV) F (pVAX.nd.f) or HN (pcDNA.nd.hn) genes separately or in combination in bi-cistronic (pIRES.nd.hn.f) constructs were evaluated in maternal antibody-positive commercial chicks. 2. Immunofluorescence and immunoperoxidase tests demonstrated the expression of both F and HN proteins in Vero cells. Real-time PCR analysis revealed the expression of HN and/or F genes in muscle, peripheral blood mononuclear cells (PBMC), spleen and liver after immunisation. 3. Chicks inoculated intramuscularly thrice (two booster doses) with pVAX.nd.f and pcDNA.nd.hn did not develop detectable haemagglutination inhibiting (HI) antibodies. In contrast, an increase in a NDV-specific cell-mediated immune response was demonstrated. 4. After challenge with virulent NDV, chicks immunised with the recombinant plasmids as well as those in control groups succumbed to Newcastle disease. 5. Based on these results, it is concluded that DNA vaccines containing HN and/or F genes fail to protect commercial chicks, possibly due to interference from maternal antibodies. PMID:18409084

Rajawat, Y S; Sundaresan, N R; Ravindra, P V; Kantaraja, C; Ratta, B; Sudhagar, M; Rai, A; Saxena, V K; Palia, S K; Tiwari, A K

2008-03-01

182

[Systemic lupus erythematosus presenting chronic relapsing polyneuropathy as the first manifestation without auto-antibodies].  

PubMed

Chronic relapsing polyneuropathy (CRPN) is an idiopathic disorder characterized by relapsing and remitting course, elevated CSF protein, slow nerve conduction and absence of systemic disease(s). Systemic lupus erythematosus (SLE), however, has been reported to manifest clinical symptoms and signs mimicking CRPN. A few authors described CRPN as a presenting manifestation or more rarely as the only illness of SLE. In these cases diagnosis of SLE was confirmed by some laboratory tests to detect auto-antibodies which were positive in subclinical SLE. We experienced a 24-year-old female whose illness started as CRPN without any auto-antibodies and recurred with autoimmune abnormalities indicating SLE. She noticed muscle weakness in the lower extremities about ten months previous to the first admission. The weakness progressed gradually and was accompanied by urinary incontinence and sensory deficits in limbs. In another hospital lumbar puncture revealed highly elevated CSF protein and she was referred to us. Neurologic examination showed sensorimotor polyneuropathy with normal blood chemistry and negative auto-antibodies. Prednisolone therapy brought out gradual improvement. She was readmitted 2 years after the first admission because of severe motor dominant polyneuropathy. Serological examination revealed positive auto-antibodies including antinuclear (ANA), anti-DNA, anti-RNP and anti-ENA antibodies. CBC showed decreased number of white blood cells. Nerve conduction velocities were markedly reduced. Again prednisolone was administrated successfully. Thereafter, she experienced several relapsing and remitting cycles. It was characteristic that deterioration of symptomatological findings such as motor weakness was always accompanied by an elevated titer of ANA and increased CSF protein in each of the cycles.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2265510

Sotomatsu, A; Tanaka, M; Yamaguchi, H; Okamoto, K; Hirai, S

1990-09-01

183

Analysis and solution of false-positives when testing CVA16 sera using an antibody assay against the EV71 virus.  

PubMed

Hand, foot and mouth disease (HFMD) in humans is caused mainly by Enterovirus 71(EV71) and Coxsackievirus A16 (CVA16). EV71 is associated with severe HFMD cases but not CVA16. Use of IgM-capture enzyme-linked immunosorbent assay (ELISA) is important for the early diagnosis of EV71 infection, but cross-reactivity of the anti-CVA16 IgM antibody with EV71 produces false-positive results. In this report, we designed a new EV71 IgM-capture ELISA method using the EV71 VP1 peptide instead of the EV71 virion as the detectable antigen, and tested sera from patients infected with EV71 or CVA16. The results showed that acute sera from 76 EV71-infected patients had similar sensitivity for virus detection (98.68%) or VP1 detection (97.37%). When acute sera from patients infected with CVA16 were used, significant differences between the two methods were observed. The cross-reactivity rate of the virus detection method was 29.4% (5/17), but no cross-reactivity was observed using the VP1 detection method. Western immunoblotting demonstrated that EV71 VP3 cross-reacted with part of the CVA16 IgM antibody. The results demonstrate that EV71 VP3 is the cross-reactive antigen in the EV71 IgM-capture ELISA when testing CVA16 sera using the virus-antibody detection method. The problem of false-positive results was resolved by using the VP1 peptide as the detectable antigen. PMID:23707400

Wang, Changbing; You, Aiping; Tian, Xingui; Zhao, Mingqi; Chen, Yi; Lin, Tao; Zheng, Jianbin; Xiao, Misi; Zhang, Yingying; Kuang, Lu; Zhou, Zhenwen; Zhu, Bing

2013-09-01

184

Prevalence of positive antibody test results for canine parvovirus (CPV) and canine distemper virus (CDV) and response to modified live vaccination against CPV and CDV in dogs entering animal shelters.  

PubMed

Canine parvovirus (CPV) and canine distemper virus (CDV) infections are relatively common in animal shelters and are important population management issues since the immune status of incoming dogs is usually unknown. This study aimed to determine the prevalence of positive antibody test results for CPV and CDV in incoming dogs aged ? 4 months and to measure antibody response over 2 weeks following vaccination with a modified live vaccine (MLV). Dogs aged 4-24 months entering an adoption-guarantee shelter (Shelter 1, n=51) and aged ? 4 months entering a limited admission shelter (Shelter 2; n=51) were enrolled. Dogs from Shelter 1 had been vaccinated with MLV at a municipal shelter 5 days before enrollment, whereas dogs from Shelter 2 had no known history of vaccination at enrollment. Sera were obtained on day 1, immediately prior to CPV/CDV MLV, and tested using an in-clinic ELISA kit to detect CPV/CDV antibodies. Dogs negative for CPV and/or CDV were retested at day 6-8 and those dogs still negative at day 6-8 were retested at day 13-15. Prior to CPV/CDV MLV on day 1, more dogs tested positive for CPV (Shelter 1 - 68.6%; Shelter 2 - 84.3%) than for CDV (Shelter 1 - 37.3%; Shelter 2 - 41.2%). On day 1, prior to MLV, all spayed/neutered animals tested CPV antibody-positive (n=17/102) and CPV antibody-positive dogs were older than serologically negative dogs (Shelter 1, P=0.0029; Shelter 2, P=0.0042). By day 13-15, almost all dogs were CPV antibody-positive (Shelter 1 - 97.9%; Shelter 2 - 100.0%) and CDV antibody-positive (Shelter 1 - 93.8%; Shelter 2 - 97.8%). MLV induces protective antibody titers against CPV/CDV in almost all dogs after 13-15 days. PMID:22261239

Litster, Annette; Nichols, Jamieson; Volpe, Allison

2012-05-25

185

Homozygosity of the Polymorphism MICA5.1 Identifies Extreme Risk of Progression to Overt Adrenal Insufficiency among 21-Hydroxylase Antibody-Positive Patients with Type 1 Diabetes  

PubMed Central

Context: Autoimmunity associated with Addison’s disease (AD) can be detected by measuring 21-hydroxylase (21OH) autoantibodies. Subjects with type 1 diabetes (T1D) are at increased risk for AD. Genetic factors including HLA-DRB1*0404 and MICA have been associated with AD in populations with and without T1D. Objective: The objective of the study was to examine the effect of the MICA5.1 allele in subjects with 21OH autoantibodies on progression to AD. Design: Two components were used: 1) a cross-sectional study with subjects with AD identified and enrolled from September 1993 to November 2008 and 2) a cohort study prospectively following up patients with T1D who screened positive for 21OH autoantibodies. Setting: Subjects were identified from the Barbara Davis Center and through the National Adrenal Diseases Foundation. Patients: Sixty-three subjects with AD were referred through the National Adrenal Diseases Foundation (AD referrals). Sixty-three subjects with positive 21OH antibodies from the Barbara Davis Center were followed up for progression to AD, and 11 were diagnosed with AD (progressors). Results: Seventy-three percent of progressors (eight of 11) and 57% of AD referrals (36 of 63) were MICA5.1 homozygous (P = ns). Overall, 59% of patients with AD (44 of 74) were MICA5.1/5.1 compared with 17% of nonprogressors (nine of 52) (P < 0.0001) and 19% of normal DR3/4-DQB1*0302 controls (64 of 336) (P < 0.0001). Conclusions: Identifying extreme risk should facilitate monitoring of progression from 21OH antibody positivity to overt AD. The HLA-DR3/0404 genotype defines high-risk subjects for adrenal autoimmunity. MICA5.1/5.1 may define those at highest risk for progression to overt AD, a feature unique to AD and distinct from T1D.

Triolo, Taylor M.; Baschal, Erin E.; Armstrong, Taylor K.; Toews, Carrie S.; Fain, Pamela R.; Rewers, Marian J.; Yu, Liping; Miao, Dongmei; Eisenbarth, George S.; Gottlieb, Peter A.; Barker, Jennifer M.

2009-01-01

186

Trastuzumab-based treatment of HER2-positive breast cancer: an antibody-dependent cellular cytotoxicity mechanism?  

Microsoft Academic Search

This study evaluated by immunohistochemistry (IHC) immune cell response during neoadjuvant primary systemic therapy (PST) with trastuzumab in patients with HER2-positive primary breast cancer. In all, 23 patients with IHC 3+ primary breast cancer were treated with trastuzumab plus docetaxel. Pathological complete and partial responses were documented for nine (39%) and 14 (61%) patients, respectively. Case-matched controls comprised patients treated

L Arnould; M Gelly; F Penault-Llorca; L Benoit; F Bonnetain; C Migeon; V Cabaret; V Fermeaux; P Bertheau; J Garnier; J-F Jeannin; B Coudert

2006-01-01

187

Is There an Association between Life Events, Postnatal Depression and Thyroid Dysfunction in Thyroid Antibody Positive Women?  

Microsoft Academic Search

Background: Postnatal depression is more common in women positive for thyroid autoantibodies, independent of thyroid hormone dysfunction, but the basis of this association is unclear.Aims: The objective of the work reported here has been to investigate from data obtained from previously published research, a possible association between life events, postnatal depression and the development of thyroid dysfunction in women who

Rossana G. Oretti; Brian Harris; John H. Lazarus; Arthur B. Parkes; Tina Crownshaw

2003-01-01

188

Hepatitis B reactivation in patients with multiple myeloma and isolated positive hepatitis B core antibody: a call for greater cognizance.  

PubMed

Hepatitis B virus (HBV) reactivation is a well-established complication of severe immunosuppression in patients with hematologic malignancy and positive hepatitis B surface antigen (HBsAg). Patients who receive high-dose chemotherapy, corticosteroids, rituximab, or have a bone marrow transplant are particularly at increased risk for HBV reactivation. However, limited information is available in the literature regarding HBV reactivation in patients with isolated anti-HBc, particularly in the setting of multiple myeloma (MM). We report two cases of HBV reactivation in MM patients with isolated anti-HBc positive with a rather atypical presentation. In conclusion, our cases highlight that clinicians need to be cognizant about this potentially fatal but preventable complication of chemotherapy and immunosuppression. PMID:24927619

Ju Dong, Yang; Mohit, Girotra; Alejandro, Restrepo; Waheed, Sarah; Barlogie, Bart; Duarte-Rojo, Andres

2014-01-01

189

Targeting 11q23 positive acute leukemia cells with high molecular weight-melanoma associated antigen-specific monoclonal antibodies  

Microsoft Academic Search

Background  Acute leukemia with 11q23 aberrations is associated with a poor outcome with therapy. The lack of efficacy of conventional\\u000a therapy has stimulated interest in developing novel strategies. Recent studies have shown that 11q23-positive acute leukemia\\u000a cells express the high molecular weight-melanoma associated antigen (HMW-MAA). This tumor antigen represents a useful target\\u000a to control growth of human melanoma tumors in patients

Allison S. Drake; Michael T. Brady; Xin Hui Wang; Sheila J. N. Sait; Justin C. Earp; Soldano Ferrone; Eunice S. Wang; Meir Wetzler

2009-01-01

190

Shared Epitope Alleles Remain A Risk Factor for Anti-Citrullinated Proteins Antibody (ACPA) - Positive Rheumatoid Arthritis in Three Asian Ethnic Groups  

PubMed Central

Background To investigate the associations between HLA-DRB1 shared epitope (SE) alleles and rheumatoid arthritis in subsets of rheumatoid arthritis defined by autoantibodies in three Asian populations from Malaysia. Methods 1,079 rheumatoid arthritis patients and 1,470 healthy controls were included in the study. Levels of antibodies to citrullinated proteins (ACPA) and rheumatoid factors were assessed and the PCR-SSO method was used for HLA-DRB1 genotyping. Results The proportion of ACPA positivity among Malay, Chinese and Indian rheumatoid arthritis patients were 62.9%, 65.2% and 68.6%, respectively. An increased frequency of SE alleles was observed in ACPA-positive rheumatoid arthritis among the three Asian ethnic groups. HLA-DRB1*10 was highly associated with rheumatoid arthritis susceptibility in these Asian populations. HLA-DRB1*0405 was significantly associated with susceptibility to rheumatoid arthritis in Malays and Chinese, but not in Indians. HLA-DRB1*01 did not show any independent effect as a risk factor for rheumatoid arthritis in this study and HLA-DRB1*1202 was protective in Malays and Chinese. There was no association between SE alleles and ACPA- negative rheumatoid arthritis in any of the three Asian ethnic groups. Conclusion The HLA-DRB1 SE alleles increase the risk of ACPA-positive rheumatoid arthritis in all three Asian populations from Malaysia.

Chun-Lai, Too; Padyukov, Leonid; Dhaliwal, Jasbir Singh; Lundstrom, Emeli; Yahya, Abqariyah; Muhamad, Nor Asiah; Klareskog, Lars; Alfredsson, Lars; Larsson, Per Tobias; Murad, Shahnaz

2011-01-01

191

Antibody-mediated rejection after adult living-donor liver transplantation triggered by positive lymphocyte cross-match combination  

PubMed Central

A 46-year-old female suffering from liver cirrhosis was referred to us for living-donor liver transplantation (LDLT). Pre-transplant lymphocyte cross-match tests were positive. The recipient showed immunoreactivity against donor human leukocyte antigen (HLA) Class I antigens, a finding confirmed by flow cytometry. Additional tests confirmed donor-specific lymphocyte immunoreactivity against HLA B 55. As no other suitable donor was available, we performed LDLT coupled with splenectomy, despite the positive cross-match. Tacrolimus, methylprednisolone and mycophenolate mofetil were used postoperatively for immunosuppression. The postoperative course was uneventful until Day 3 when blood tests showed disorders in liver function and the patient’s condition suddenly worsened. Although intensive care (including plasma exchange) was given, her condition continued to deteriorate. Flow cytometry initially showed that immunoreactivity against Class I antigens was down-regulated immediately after LDLT, but further testing showed that it had increased again. We diagnosed humoral rejection based on clinical, immunological and histopathological findings and suggest that this was mediated by an immune response to donor-specific antigens. The patient experienced multi-organ failure and died on post-operative Day 9.

Hori, Tomohide; Egawa, Hiroto; Uemoto, Shinji

2012-01-01

192

Importance of the dense fine speckled pattern on HEp2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases  

Microsoft Academic Search

The presence of anti-nuclear antibodies (ANA) is a hallmark of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and was recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of serum samples

Michael Mahler; John G. Hanly; Marvin J. Fritzler

193

Significant Association between Serum Interleukin-6 and Helicobacter pylori Antibody Levels among H. pylori-Positive Japanese Adults  

PubMed Central

Background. Interleukin-6 (IL-6) is a multifunctional cytokine produced by many types of cells. Inflammation plays a key role in the pathogenesis of atherosclerosis that is an underlying cause of coronary heart disease (CHD). Since the 1990s, some studies have shown an association between H. pylori infection and CHD, which may be mediated by inflammation. Therefore, this study aimed to evaluate the association between serum anti-H. pylori IgG levels and serum IL-6 levels in H. pylori-infected adults. Methods. We enrolled 158 subjects who visited a clinic located in an urban area to be tested for H. pylori infection, using the 13C-urea breath test, and who were found to be infected and subsequently received eradication. Results. The geometric mean serum IL-6 level was 1.78?pg/mL for men, 1.57?pg/mL for women, and 1.64?pg/mL overall. Logarithms of serum IL-6 levels were positively correlated with logarithms of serum H. pylori IgG levels (r = 0.24, P = 0.002). In multiple linear regression analysis adjusting for sex and age, the serum IL-6 level was still significantly associated with the IgG level in all subjects (? = 0.18, P = 0.012). Conclusion. Higher H. pylori IgG levels were significantly associated with higher serum IL-6 levels among H. pylori-infected individuals.

Nakagawa, Hiroko; Tamura, Takashi; Mitsuda, Yoko; Goto, Yasuyuki; Kamiya, Yoshikazu; Kondo, Takaaki; Wakai, Kenji; Hamajima, Nobuyuki

2013-01-01

194

Immunoglobulin allotype gene polymorphisms in systemic sclerosis: interactive effect of MHC class II and KM genes on anticentromere antibody production  

PubMed Central

OBJECTIVE—To examine potential interactions between immunoglobulin (Ig)allotype gene polymorphisms and susceptibility to systemic sclerosis (SSc) as well as serological expression in SSc patients.?METHODS—IgG heavy chain allotypes G1M(f, z), G2M(n+, n-), G3M(b, g) and Ig light chain allotype KM(1, (1, 2), 3) were genotyped in 105 Japanese SSc patients and 47 race matched normal controls using polymerase chain reaction (PCR) based methods. Associations of each Ig allotype with SSc related antinuclear antibodies were examined in combination with or without MHC class II alleles.?RESULTS—GM/KM genotypic and allelic frequencies were similar in SSc patients and in normal controls. Frequencies of G1M(f) and G2M(n+) were significantly decreased in anticentromere antibody (ACA) positive SSc patients compared with ACA negative SSc patients (p = 0.04 and 0.02, respectively). Conversely, the presence of DQB1*0501 and KM(1, 2) significantly increased the risk of ACA positivity.?CONCLUSION—Ig allotype gene polymorphisms were not associated with susceptibility to SSc. Instead, the results suggested that MHC class II and KM genes are associated with autoimmune responses by interactively promoting the production of ACA.?? Keywords: autoantibody; immunoglobulin allotype; major histocompatibility complex; scleroderma

Kameda, H.; Pandey, J.; Kaburaki, J.; Inoko, H.; Kuwana, M.

1998-01-01

195

ABO-Incompatible Living Donor Liver Transplantation from Hepatitis B Core Antibody Positive Donor to Hepatitis C Liver Cirrhosis Recipient: A Case Report  

PubMed Central

Herein, we describe an extremely rare experience of a patient with liver cirrhosis from hepatitis C virus (LC-HCV) who underwent an ABO-incompatible living donor liver transplantation (ABO-I-LDLT) using a hepatitis B core antibody (HBc-Ab) positive donor's liver graft. A 47-year-old Japanese woman with end stage LC-HCV, as a recipient, was preoperatively administered rituximab, mycophenolate mofetil, and steroids without plasma exchange. A routine ABO-I-LDLT procedure was applied using her daughter's HBc-Ab positive liver graft. Prophylaxis of the hepatitis B virus (HBV) infection using hepatitis B immunoglobulin (HBIG) and entecavir had been properly administered. Three months after the ABO-I-LDLT, HCV hepatitis relapsed. To date, this patient has been under antiviral therapy and prophylaxis of HBV infection using HBIG, while entecavir has been continued. The cognitions and techniques with regard to ABO-I-LDLT, prophylaxis of HBV cross infection, various patterns of immunosuppression, and antiviral therapy for HCV relapse are indispensable in managing a transplant recipient. According to the prophylaxis of HBV cross infection under ABO-I-LDLT, it may be very important to keep the HBs-Ab titer higher than usual for HBV naïve recipients, because severe systemic immunosuppression can cause de novo hepatitis.

Nitta, Hiroyuki; Sasaki, Akira; Hasegawa, Yasushi; Wakabayashi, Go

2014-01-01

196

Antinuclear autoantibodies are more prevalent in COPD in association with low body mass index but not with smoking history  

Microsoft Academic Search

BackgroundChronic obstructive pulmonary disease (COPD) is associated with a higher prevalence of antinuclear autoantibodies (ANAs). However, a significant subgroup of patients is ANA negative. It remains to be determined which patient groups carry autoantibodies.MethodsThe association of smoking behaviour, disease status, gender, age and body mass index (BMI) with the presence of autoantibodies in the serum was determined in 124 patients

H P J Bonarius; C A Brandsma; H A M Kerstjens; J A Koerts; M Kerkhof; E Nizankowska-Mogilnicka; C Roozendaal; D S Postma; W Timens

2010-01-01

197

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

PubMed

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. PMID:20521422

Yamazaki, Masakatsu

2009-01-01

198

Anti-nuclear weapons activism in the United States and Great Britain: a comparative analysis  

SciTech Connect

This study is a response to the lacuna in empirical research into political activism and the nuclear issue and seeks to ascertain the social and value characteristics, political attitudes, and political behavior of activists in the United States and Great Britain. Consideration is also given to gender differences in light of evidence of an emerging gender gap in these two countries. The study investigates the common forces cited in two sets of literature - post-industrialism and anti-nuclear weapons movements - which provide a framework for analysis. Survey research data is employed to assess cross-national similarities and differences. The findings obtained indicate that while American and British activists exhibit common social and value characteristics, British activists appear more integrated in their political opposition to nuclear weapons compared with their American counterparts. Survey results indicate that the political-action repertoire of these activists is quite diverse, suggesting a new style of politics in advanced industrial democracies. Gender-based analysis reveals two important findings. First, activist American men differ significantly from the other three social groups in their attitudes towards nuclear weapons. Second, activist women in both national settings participate at a level equal to or exceeding that of activist men.

Sussman, G.

1987-01-01

199

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

PubMed

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. PMID:16749477

Reitzig, Andreas

2006-01-01

200

Elevated levels of IgM and IgA antibodies to Proteus mirabilis and IgM antibodies to Escherichia coli are associated with early rheumatoid factor (RF)-positive rheumatoid arthritis  

Microsoft Academic Search

Objective. Antibodies to Proteus mirabilis were previously detected in patients with established rheumatoid arthritis (RA). We examined the prevalence of antibodies to P. mirabilis and their associations with RA in early synovitis patients. Methods. Two hundred and forty-six patients with inflammatory arthritis for less than 1 yr were prospectively evaluated for 1 yr. Of these patients, 30% had rheumatoid factor

M. M. Newkirk; R. Goldbach-Mansky; B. W. Senior; J. Klippel; H. R. Schumacher Jr; H. S. El-Gabalawy

2005-01-01

201

EBV-positive diffuse large B-cell lymphoma in a patient with primary Sj?gren's syndrome and membranous glomerulonephritis  

PubMed Central

Background Sjögren’s syndrome is a systemic autoimmune disease in which lymphatic cells destroy the salivary and lacrimal glands. Glomerulonephritis is thought to be a rare occurrence in primary Sjögren’s syndrome. Furthermore, concurrent glomerular involvement and lymphoma in patients with Sjögren’s syndrome has seldom been reported. Case presentation A 52-year-old woman with primary Sjögren’s syndrome developed membranous glomerulonephritis and Epstein-Barr virus-positive diffuse large B-cell lymphoma (DLBCL). She was diagnosed with Sjögren’s syndrome based on the dry eyes, dry mouth, positive anti-nuclear antibody test, anti-Ro (SS-A) antibody, salivary gland biopsy, and salivary scintigraphy. Moreover, renal biopsy confirmed the diagnosis of membranous glomerulonephritis. Three months later, her small bowel was perforated with pneumoperitoneum, and the biopsy revealed Epstein-Barr virus-positive DLBCL. Conclusions We observed the first case of primary Sjögren’s syndrome associated with Epstein-Barr Virus-positive DLBCL and membranous glomerulonephritis. Because of the possibility of malignancy-associated membranous glomerulonephritis in patients with primary Sjögren’s syndrome, we should be careful and examine such patients for hidden malignancy.

2012-01-01

202

Combined vaccination and immunostimulatory antibodies provides durable cure of murine melanoma and induces transcriptional changes associated with positive outcome in human melanoma patients  

PubMed Central

We have developed a recombinant adenovirus vaccine encoding dopachrome tautomerase (rHuAd5-hDCT) that produces robust DCT-specific immunity, but only provides modest suppression of murine melanoma. In the current study, an agonist antibody against 4-1BB was shown to enhance rHuAd5-hDCT efficacy and evoke tumor regression, but most tumors ultimately relapsed. The vaccine triggered upregulation of the immune inhibitory PD-1 signaling pathway and PD-1 blockade dramatically enhanced the rHuAd5-hDCT + anti-4-1BB strategy, resulting in complete regression of growing tumors in > 70% of recipients. The impact of the combined anti-4-1BB/anti-PD-1 treatment did not manifest as a dramatic enhancement in either the magnitude or functionality of DCT-specific tumor infiltrating lymphocytes relative to either treatment alone. Rather, a synergistic enhancement in intratumoral cytokine expression was observed, suggesting that the benefit of the combined therapy was a local event within the tumor. Global transcriptional analysis revealed immunological changes within the tumor following the curative vaccination, which extended beyond the T cell compartment. We identified an immune signature of 85 genes associated with clearance of murine melanoma that correlated with improved survival outcome in two independent cohorts of human melanoma patients. Our data reinforce the concept that successful vaccination must overcome local hurdles in the tumor microenvironment that are not manifest within the periphery. Further, tumor rejection following vaccination involves more than simply T cells. Finally, the association of our immune signature with positive survival outcome in human melanoma patients suggests that similar vaccination strategies may be promising for melanoma treatment.

McGray, A.J. Robert; Bernard, Dannie; Hallett, Robin; Kelly, Ryan; Jha, Mayank; Gregory, Caitlin; Bassett, Jennifer D.; Hassell, John A.; Pare, Guillaume; Wan, Yonghong; Bramson, Jonathan L.

2012-01-01

203

Failure of A Novel, Rapid Antigen and Antibody Combination Test to Detect Antigen-Positive HIV Infection in African Adults with Early HIV Infection  

Microsoft Academic Search

BackgroundAcute HIV infection (prior to antibody seroconversion) represents a high-risk window for HIV transmission. Development of a test to detect acute infection at the point-of-care is urgent.MethodsVolunteers enrolled in a prospective study of HIV incidence in four African cities, Kigali in Rwanda and Ndola, Kitwe and Lusaka in Zambia, were tested regularly for HIV by rapid antibody test and p24

William Kilembe; Michelle Keeling; Etienne Karita; Shabir Lakhi; Paramesh Chetty; Matt A. Price; Heeran Makkan; Mary Latka; Morongwe Likoti; Kenneth Ilukui; Mackenzie Hurlston; Susan Allen; Gwynn Stevens; Eric Hunter

2012-01-01

204

Characterization of a new mitochondrial antigen-antibody system (M9/anti-M9) in patients with anti-M2 positive and anti-M2 negative primary biliary cirrhosis.  

PubMed Central

A new antimitochondrial antibody (AMA) against an outer membrane associated antigen on liver mitochondria was detected by ELISA in sera from patients with primary biliary cirrhosis (PBC). This antibody was named anti-M9. There is evidence that it is a partial organ-specific antibody as shown by absorption studies using submitochondrial particles prepared from heart, liver and kidney. A purified M9-fraction was prepared by subjecting a 100,000 g supernatant from rat liver mitochondria to ion exchange chromatography. This fraction was devoid of the previously described M1-M8 antigens except for M4. Trypsin treatment of the fraction enabled a distinction to be made between M4 which was protease resistant, and M9 which was trypsin sensitive. Applying this M9-fraction in Western blotting anti-M9 positive sera recognized two proteins at a molecular weight of 98 kD and 59 kD. Anti-M9 antibodies were detected in 37% of 156 anti-M2 positive as well as in 82% of 22 anti-M2 negative patients with histologically proven PBC. It is concluded that anti-M9 is a new AMA type in PBC which may be helpful especially for the early diagnosis of PBC in patients who are still anti-M2 negative. As one of the earliest immunological signs in PBC further characterization of M9 could provide new insights into the etiopathogenesis of the disease. Images Fig. 3

Klein, R; Berg, P A

1988-01-01

205

Predictive value of intravenous glucose tolerance test insulin secretion less than or greater than the first percentile in islet cell antibody positive relatives of Type 1 (insulin-dependent) diabetic patients  

Microsoft Academic Search

Summary  We have followed-up 35 islet cell antibody-positive first degree relatives of patients with Type 1 (insulin-dependent) diabetes mellitus for an average of 1,300 days with sequential intravenous glucose tolerance tests. At the time of analysis and manuscript submission approximately half (18 of 35) had developed diabetes during follow-up. At initial intravenous glucose tolerance test, 11 had a 1+3 min insulin

P. Vardi; L. Crisa; R. A. Jackson; R. Dumont Herskowitz; J. I. Wolfsdorf; D. Einhorn; L. Linarelli; R. Dolinar; S. Wentworth; S. J. Brink; H. Starkman; J. S. Soeldner; G. S. Eisenbarth

1991-01-01

206

Relationship between Presence of Cows with Milk Positive for Mycobacterium avium subsp. paratuberculosis-Specific Antibody by Enzyme-Linked Immunosorbent Assay and Viable M. avium subsp. paratuberculosis in Dust in Cattle Barns  

PubMed Central

Paratuberculosis, or Johne's disease, in cattle is caused by Mycobacterium avium subsp. paratuberculosis, which has recently been suspected to be transmitted through dust. This longitudinal study on eight commercial M. avium subsp. paratuberculosis-positive dairy farms studied the relationship between the number of cows with M. avium subsp. paratuberculosis antibody-positive milk and the presence of viable M. avium subsp. paratuberculosis in settled-dust samples, including their temporal relationship. Milk and dust samples were collected in parallel monthly for 2 years. M. avium subsp. paratuberculosis antibodies in milk were measured by enzyme-linked immunosorbent assay (ELISA) and used as a proxy for M. avium subsp. paratuberculosis shedding. Settled-dust samples were collected by using electrostatic dust collectors (EDCs) at six locations in housing for dairy cattle and young stock. The presence of viable M. avium subsp. paratuberculosis was identified by liquid culture and PCR. The results showed a positive relationship (odds ratio [OR], 1.2) between the number of cows with ELISA-positive milk and the odds of having positive EDCs in the same airspace as the adult dairy cattle. Moreover, the total number of lactating cows also showed an OR slightly above 1. This relationship remained the same for settled-dust samples collected up to 2 months before or after the time of milk sampling. The results suggest that removal of adult cows with milk positive for M. avium subsp. paratuberculosis-specific antibody by ELISA might result in a decrease in the presence of viable M. avium subsp. paratuberculosis in dust and therefore in the environment. However, this decrease is likely delayed by several weeks at least. In addition, the data support the notion that M. avium subsp. paratuberculosis exposure of young stock is reduced by separate housing.

Chuchaisangrat, Ruj; Nielen, Mirjam; Koets, Ad P.

2013-01-01

207

Anti-citrullinated protein antibody-positive rheumatoid arthritis associated with RS3PE syndrome-like symptoms and an elevated serum vascular endothelial growth factor level in a patient with myasthenia gravis.  

PubMed

A 73-year-old man with a history of myasthenia gravis (MG) was diagnosed with rheumatoid arthritis (RA) based on a history of polyarthritis and positivity for anti-citrullinated protein antibodies (ACPA). He presented with a high level of serum vascular endothelial growth factor (VEGF) and RS3PE syndrome-like pitting edema in the extremities, which improved following treatment with low-dose prednisolone. This is an interesting case of ACPA-positive RA associated with RS3PE syndrome-like pitting edema and a high VEGF level. PMID:24739614

Horai, Yoshiro; Honda, Mai; Nishino, Ayako; Nakashima, Yoshikazu; Suzuki, Takahisa; Kawashiri, Shin-Ya; Ichinose, Kunihiro; Tamai, Mami; Nakamura, Hideki; Motomura, Masakatsu; Origuchi, Tomoki; Kawakami, Atsushi

2014-01-01

208

Autoantibodies in sera from patients with L-tryptophan-associated eosinophilia-myalgia syndrome. Demonstration of unique antigen-antibody specificities.  

PubMed

The purpose of this study was to determine whether specific autoantibodies could be identified that are associated with eosinophilia-myalgia syndrome (EMS). Sera from 44 patients with EMS were tested by indirect immunofluorescence, immunodiffusion against calf thymus extract, and immunoprecipitation from HeLa cell extract. Antinuclear antibodies were detected in the sera of 24/39 patients with EMS (61.5%) by indirect immunofluorescence against HEp-2 cells. Seven patients (16%) were demonstrated to have specific autoantibodies by immunoprecipitation in which at least two shared patterns were noted. In three sera immunoprecipitation identified a similar 63-kDa band (Ab-1). An additional four sera shared a pattern of bands consisting of a strong 110-kDa protein and a weak 95-kDa protein (Ab-2). Absorption of HeLa extract with a strongly positive Ab-2 serum confirmed that the four patients shared the same antibody. In conclusion, the detection of these autoantibodies provides evidence of autoimmunity in EMS, and may distinguish this syndrome from clinically related conditions. PMID:7542184

Kaufman, L D; Varga, J; Gomez-Reino, J J; Jimenez, S; Targoff, I N

1995-08-01

209

High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 are significant target antigens of perinuclear anti-neutrophil cytoplasmic antibodies in autoimmune hepatitis  

PubMed Central

BACKGROUND—High mobility group (HMG) non-histone chromosomal proteins HMG1 and HMG2 have been identified as novel antigens of perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCAs), and the existence of anti-HMG1 and anti-HMG2 antibodies in a population of patients with ulcerative colitis has been reported.?AIMS—To investigate whether HMG1 and HMG2 are target antigens for p-ANCAs in autoimmune hepatitis (AIH).?PATIENTS—Serum samples from 28 patients with AIH, 44 patients with primary biliary cirrhosis (PBC), 27 patients with chronic hepatitis C, and 23 patients with chronic hepatitis B were tested.?METHODS—ANCAs were detected by routine indirect immunofluorescence (IIF). Anti-HMG1 and anti-HMG2 antibodies were assayed by enzyme linked immunosorbent assay.?RESULTS—p-ANCAs were detected in 89% (25/28) of patients with AIH, 36% (16/44) of patients with PBC, 11% (3/27) of patients with chronic hepatitis C, and 13% (3/23) of patients with chronic hepatitis B. Anti-HMG1 and/or anti-HMG2 antibodies were detected in 89% (25/28) of patients with AIH, 70% (31/44) with PBC, 26% (7/27) with chronic hepatitis C, and 9% (2/23) with chronic hepatitis B. In AIH, anti-HMG1 and/or anti-HMG2 antibodies were detected in 96% (24/25) of p-ANCA positive patients. The p-ANCA staining pattern detected by IIF using sera from patients with AIH disappeared or decreased in titre after preincubation with a mixture of HMG1/HMG2. The presence and titres of those antibodies in AIH correlated significantly with those of p-ANCA, but not with those of anti-nuclear antibody or anti-smooth muscle antibody.?CONCLUSIONS—HMG1 and HMG2 are significant target antigens of p-ANCA in AIH.???Keywords: perinuclear anti-neutrophil cytoplasmic antibodies; chromosomal proteins; high mobility group 1 and 2; autoimmune; hepatitis

Sobajima, J; Ozaki, S; Uesugi, H; Osakada, F; Inoue, M; Fukuda, Y; Shirakawa, H; Yoshida, M; Rokuhara, A; Imai, H; Kiyosawa, K; Nakao, K

1999-01-01

210

Antibody libraries  

US Patent & Trademark Office Database

The present invention relates to the production of antibody libraries. In particular, the present invention relates to the use of integrating retroviral vectors to generate libraries comprising a plurality of combinations of antibody light chains and heavy chains. The present invention thus provides improved methods of generating and screening antibody libraries comprising large numbers of unique antibodies.

2012-07-17

211

The PTPN22 1858C\\/T polymorphism is associated with anti-cyclic citrullinated peptide antibody-positive early rheumatoid arthritis in northern Sweden  

Microsoft Academic Search

The PTPN22 1858C\\/T polymorphism has been associated with several autoimmune diseases including rheumatoid arthritis (RA). We have shown that carriage of the T variant (CT or TT) of PTPN22 in combination with anti-cyclic citrullinated peptide (anti-CCP) antibodies highly increases the odds ratio for developing RA. In the present study we analysed the association between the PTPN22 1858C\\/T polymorphism and early

Heidi Kokkonen; Martin Johansson; Lena Innala; Erik Jidell; Solbritt Rantapää-Dahlqvist

2007-01-01

212

Serum Antibodies from a Subset of Horses Positive for Babesia caballi by Competitive Enzyme-Linked Immunosorbent Assay Demonstrate a Protein Recognition Pattern That Is Not Consistent with Infection  

PubMed Central

Tick-borne pathogens that cause persistent infection are of major concern to the livestock industry because of transmission risk from persistently infected animals and the potential economic losses they pose. The recent reemergence of Theileria equi in the United States prompted a widespread national survey resulting in identification of limited distribution of equine piroplasmosis (EP) in the U.S. horse population. This program identified Babesia caballi-seropositive horses using rhoptry-associated protein 1 (RAP-1)–competitive enzyme-linked immunosorbent assay (cELISA), despite B. caballi being considered nonendemic on the U.S. mainland. The purpose of the present study was to evaluate the suitability of RAP-1–cELISA as a single serological test to determine the infection status of B. caballi in U.S. horses. Immunoblotting indicated that sera from U.S. horses reacted with B. caballi lysate and purified B. caballi RAP-1 protein. Antibody reactivity to B. caballi lysate was exclusively directed against a single ?50-kDa band corresponding to a native B. caballi RAP-1 protein. In contrast, sera from experimentally and naturally infected horses from regions where B. caballi is endemic bound multiple proteins ranging from 30 to 50 kDa. Dilutions of sera from U.S. horses positive by cELISA revealed low levels of antibodies, while sera from horses experimentally infected with B. caballi and from areas where B. caballi is endemic had comparatively high antibody levels. Finally, blood transfer from seropositive U.S. horses into naive horses demonstrated no evidence of B. caballi transmission, confirming that antibody reactivity in cELISA-positive U.S. horses was not consistent with infection. Therefore, we conclude that a combination of cELISA and immunoblotting is required for the accurate serodiagnosis of B. caballi.

Awinda, Peter O.; Mealey, Robert H.; Williams, Laura B. A.; Conrad, Patricia A.; Packham, Andrea E.; Reif, Kathryn E.; Grause, Juanita F.; Pelzel-McCluskey, Angela M.; Chung, Chungwon; Bastos, Reginaldo G.; Kappmeyer, Lowell S.; Howe, Daniel K.; Ness, SallyAnne L.; Knowles, Donald P.

2013-01-01

213

Antiphospholipid antibodies during 6-month treatment with infliximab: A preliminary report  

PubMed Central

Background The introduction of tumor necrosis factor (TNF) antagonists (adalimumab, infliximab, and etanercept) was a major advance and was highly important and beneficial in most rheumatoid arthritis (RA) patients. The adverse effects of this treatment are infrequent, but include opportunistic intracellular infection (especially the reactivation of latent Mycobacterium tuberculosis); exacerbation of demyelinating disorders; and the production of various types of antibodies such as antinuclear antibodies (ANA) or double-stranded DNA autoantibodies (dsDNA) and antiphospholipid antibodies (aPL) such as anti-cardiolipin antibodies (aCL) and anti-B2GP-I antibodies (B2GP-I). The aim of the study was to determine the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Material/Methods We determined the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Results We observed a statistically important increase only in the group of B2GP-I IgM (p<0.05). There are contradictory results concerning the ability of infliximab to induce aPL, but most authors confirm this phenomenon. Conclusions Further investigations are needed to determine if the new aPL appears in patients with ?2-GPI gene polymorphisms such as leucine-to-valine substitution at position 247, which can lead to a conformational changes in ?2-GPI protein, leading to aPL synthesis. The role of aPL in pathogenesis of APS is still unclear, but we should remember the immunogenic aspect of TNF antagonist treatment. Therefore, we recommend early detection of aPL and observation of the patient, paying special attention to signs and symptoms of thromboembolism.

Kolarz, Bogdan; Majdan, Maria; Darmochwal-Kolarz, Dorota A.; Dryglewska, Magdalena

2014-01-01

214

Antiphospholipid antibodies during 6-month treatment with infliximab: A preliminary report.  

PubMed

Background The introduction of tumor necrosis factor (TNF) antagonists (adalimumab, infliximab, and etanercept) was a major advance and was highly important and beneficial in most rheumatoid arthritis (RA) patients. The adverse effects of this treatment are infrequent, but include opportunistic intracellular infection (especially the reactivation of latent Mycobacterium tuberculosis); exacerbation of demyelinating disorders; and the production of various types of antibodies such as antinuclear antibodies (ANA) or double-stranded DNA autoantibodies (dsDNA) and antiphospholipid antibodies (aPL) such as anti-cardiolipin antibodies (aCL) and anti-B2GP-I antibodies (B2GP-I). The aim of the study was to determine the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Material and Methods We determined the prevalence of aCL and B2GP-I in IgM and IgG classes, using ELISA tests, during 6 months of follow-up in patients with refractory RA successfully treated with infliximab. Results We observed a statistically important increase only in the group of B2GP-I IgM (p<0.05). There are contradictory results concerning the ability of infliximab to induce aPL, but most authors confirm this phenomenon. Conclusions Further investigations are needed to determine if the new aPL appears in patients with ?2-GPI gene polymorphisms such as leucine-to-valine substitution at position 247, which can lead to a conformational changes in ?2-GPI protein, leading to aPL synthesis. The role of aPL in pathogenesis of APS is still unclear, but we should remember the immunogenic aspect of TNF antagonist treatment. Therefore, we recommend early detection of aPL and observation of the patient, paying special attention to signs and symptoms of thromboembolism. PMID:25027437

Kolarz, Bogdan; Majdan, Maria; Darmochwal-Kolarz, Dorota A; Dryglewska, Magdalena

2014-01-01

215

Monoclonal antibodies and immobilized antibodies  

Microsoft Academic Search

Antibodies in both their free and immobilized state have been the object of considerable industrial and academic interest.\\u000a A variety of methods are used for preparing and immobilizing antibodies. Applications for monoclonal antibodies include the\\u000a preparation of therapeutics, diagnostics, and in affinity fractionation. Recent US patents on monoclonal and immobilized antibodies\\u000a and scientific literature on monoclonal antibodies are surveyed. A

Robert J. Linhardt; C. W. Abell; R. M. Denney; B. W. Altrock; R. Auerbach; S. D. Bernal; R. E. Canfield; P. H. Ehrlich; W. R. Moyle; T. S. Chan; T. W. Chang; N. T. Chang; J. A. Cidlowski; M. D. Viceps; R. J. Cote; D. M. Morrissey; A. N. Houghton; E. J. Beattie; H. F. Oettgen; L. J. Old; C. M. Croce; R. S. Cubicciotti; A. E. Karu; R. M. Krauss; J. S. Cullor; A. Deutsch; H. Brandwein; H. Platt; D. M. Hunter; A. Dubitsky; S. M. Durham; F. A. Dolbeare; J. W. Gray; G. R. Dreesman; C. E. Kendall; J. C. Egrie; A. R. Frackelton; H. N. Eisen; A. H. Ross; S. Gay; G. Geirnaert; J. E. Geltosky; E. H. Goldberg; E. Goldwasser; C. Kavinsky; T. L. Weiss; H. G. Gratzner; B. Hampar; M. Zweig; S. D. Showalter; H. H. Handley; M. C. Glassy; Y. Hagiwara; H. Hagiwara; C. M. Huang; S. N. Cohen; J. V. Hughes; E. M. Scolnick; J. E. Tomassini; R. Jefferis; J. Steensgaard; H. S. Kaplan; N. N. H. Teng; K. S. Earn; R. F. Calvo; L. Kass; J. R. Kettman; M. V. Norgard; M. B. Khazaeli; W. H. Beierwaltes; B. G. England; P. C. Kung; G. Goldstein; L. Lanier; J. Phillips; N. L. Warner; J. W. Larrick; A. R. Raubitschek; K. E. Truitt; H. Lazarus; J. F. Schwaber; J. Lewicki; C. Lewis; J. V. Olander; W. R. Tolbert; E. L. Milford; C. B. Carpenter; J. M. Paradysz; D. F. Mosher; J. L. Mulshine; J. D. Minna; K. A. Murray; D. M. Neville; R. J. Youle; M. Nicolson; I. Pastan; M. C. Willingham; D. J. Fitzgerald; A. Pucci; A. M. Smithyman; M. B. Slade; P. W. French; G. Wijffels; C. S. Pukel; K. O. Lloyd; L. R. Travassos; W. G. Dippold; R. P. Reckel; J. L. Harris; R. Wellerson; S. M. Shaw; P. M. Kaplan; E. L. Reinherz; S. F. Schlossman; S. C. Mener; J. Sakamoto; C. C. Cordon; E. Friedman; C. L. Finstad; W. E. Enker; M. R. Melamed; J. F. Oettgen; P. J. Scannon; L. E. Spitler; H. M. Lee; R. T. Kawahata; R. P. Mischak; J. Schlom; D. Colcher; M. Nuti; P. H. Hand; F. Austin; G. D. Shockman; D. E. Jackson; W. Wong; Z. Steplewski; H. Koprowski; M. Herlyn; M. Strand; I. S. Trowbridge; D. L. Urdal; C. J. March; S. K. Dower; J. R. Wands; V. R. Zurawski; C. A. White; R. Dulbecco; W. R. Allen; E. C. Arnold; M. Flasher; H. H. Freedman; T. D. Heath; P. Shek; D. Papahadjopoulos; M. Ikeda; S. Sakamoto; K. Suzuki; M. Kuboyama; Y. Harada; A. Kawashiri; E. Takahashi; H. S. Lee; S. Margel; R. C. Nowinski; A. S. Hoffman; J. W. Peterson; K. B. Platt; D. E. Reed; F. X. Real; M. J. Mattes; P. O. Livingston; A. Rembaum; R. C. K. Yen; R. Rosenstein; B. Schneider

1987-01-01

216

Anti-nuclear autoantibodies: clinical utility for diagnosis, prognosis, monitoring, and planning of treatment strategy in systemic immunoinflammatory diseases.  

PubMed

The determination of serum autoantibodies to nuclear and cytoplasmic cell components is relevant to the diagnosis of chronic immunoinflammatory disorders. Detection is based on screening methods that allow antibody binding to intact cell structures, followed by use of assays to demonstrate their antigen target specificity. The results can be used to help clinicians set diagnosis and estimate prognosis, plan further diagnostic work-up, monitoring strategy and sometimes therapeutic approach. To obtain such accuracy of use clinicians need to be involved in revealing the differential diagnostic potential of the autoimmune serology test programme by furnishing detailed clinical data on patients from whom serum samples have been obtained. Borders between positive and negative values should aim at attaining a high diagnostic specificity towards clinically important disease controls. PMID:16195158

Wiik, A S

2005-01-01

217

Role of auto-antibodies for the diagnosis of chronic cholestatic liver diseases.  

PubMed

Auto-antibodies are an integral part of the diagnostic armentarium in chronic cholestatic liver disorders, such as primary sclerosing cholangitis (PSC), primary biliary cirrhosis (PBC),auto-immune cholangitis, or overlap syndromes among these disorders. However, care should be taken not to overestimate the diagnostic specificity. Auto-antibodies to mitochondrial antigens(AMAs) with reactivity to the E2 subunit of the pyruvate dehydrogenase complex represent the hallmark antibody for the diagnosis of PBC, whereas antinuclear antibodies (ANAs)with low disease specificity are found in up to 50% of these sera. Antibodies that recognize nuclear envelope proteins exert a similarly high diagnostic specificity as AMA in PBC but occur at a rather low prevalence. The role of auto-antibodies is less well-studied for patients with PSC, but there is growing evidence that only antineutrophil cytoplasmic antibodies(ANCAs) are of relevant diagnostic significance. In contrast, auto-antibodies-particularlyAMAs-do not contribute to the diagnosis of auto-immune cholangitis, whereas ANCAs,ANAs, smooth muscle antibodies, and AMAs are of varying significance in PBC-auto-immune hepatitis (AIH) or PSC-AIH overlap syndromes. It has been widely accepted that the course of the auto-antibody serum end point titers are not suited for the clinical management of patients with chronic cholestatic liver disorders. Additionally, auto-antibodies in these disorders usually do not contribute to the immunopathogenesis of the disease. PMID:15879618

Terjung, Birgit; Spengler, Ulrich

2005-04-01

218

One-Step 2-Minute Test To Detect Typhoid-Specific Antibodies Based on Particle Separation in Tubes  

PubMed Central

Typhoid fever is caused by Salmonella typhi. Detection of anti-S. typhi antibodies in the patient is a useful diagnostic aid. Among the various methods developed over the years for this purpose, the Widal test, based on bacterial agglutination, has remained the most widely used, even though it is neither specific nor sensitive. Its popularity stems from the fact that it is simple to use and inexpensive. We describe a new test which also uses a simple one-step procedure but is more rapid and accurate than the Widal. The new test (TUBEX) detects anti-Salmonella O9 (both immunoglobulin M [IgM] and IgG) antibodies in patients by inhibiting the binding between an anti-O9 IgM monoclonal antibody (MAb) conjugated to colored latex particles and S. typhi lipopolysaccharide (LPS) conjugated to magnetic latex particles. The reactants are mixed in a specially designed microtube for 2 min, and the result is read based on the resultant color of the supernatant following forced sedimentation of the magnetic beads. In the absence of inhibitory antibodies, there is a color change (from blue to red) due to cosedimentation of the indicator particles with the magnetic particles, whereas if these antibodies are present, they prevent such a change to a degree dependent on their concentration. Preliminary examination of TUBEX using the anti-O9 MAb and irrelevant MAbs as inhibitors revealed the test to be specific and reproducible, with an analytical sensitivity of 16 ?g per ml of antibody. The reagents remained stable for at least 9 months when kept at 4°C. In the examination of 16 stored sera obtained from 14 patients with proven cases of typhoid fever and 78 serum samples from 75 subjects without typhoid fever, TUBEX was found to be 100% sensitive and 100% specific. The nontyphoid group comprised 26 healthy blood donors, 30 antinuclear antibody (ANA)-negative patients, 9 ANA-positive patients, of whom 1 was positive for anti-DNA antibody, 4 typhus patients, and 6 septicemic patients. In addition, the sera obtained from 11 patients clinically diagnosed as having typhoid fever were all positive in the test. The TUBEX results correlated to some extent, albeit insignificantly (r = 0.38, P = 0.07), with those of an enzyme-linked immunoassay (ELISA) which used a similar detection format (inhibition) and reagents (S. typhi LPS and anti-O9 antibody). TUBEX correlated very well with ELISAs which detected anti-S. typhi LPS IgM (r = 0.58, P = 0.003) or IgG (r = 0.54, P = 0.006) antibodies from the typhoid patients. There was no correlation with the Widal test. The TUBEX test, if performed on slides (instead of tubes) or with soluble antigen (instead of antigen-conjugated magnetic beads), suffered significantly in sensitivity. Direct agglutination tests using LPS-conjugated indicator particles performed either on slides or in microwells also failed to detect antibodies from the majority of typhoid patients. Thus, TUBEX appears to be well designed and well suited for use in the laboratory or by the bedside as a simple, rapid aid to the routine diagnosis of typhoid fever.

Lim, Pak-Leong; Tam, Frankie C. H.; Cheong, Yuet-Meng; Jegathesan, M.

1998-01-01

219

Monoclonal Antibodies.  

ERIC Educational Resources Information Center

Monoclonal antibodies have provided an exciting addition to the "armory" of the molecular biologist and immunologist. This article discusses briefly the concept of, techniques available for, production of, and possible uses of monoclonal antibodies. (Author)

Killington, R. A.; Powell, K. L.

1984-01-01

220

Expression of Recombinant Antibodies  

PubMed Central

Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications.

Frenzel, Andre; Hust, Michael; Schirrmann, Thomas

2013-01-01

221

A study of anti-poly (ADP-ribose) antibodies and an anti-DNA antibody idiotype and other immunological abnormalities in lupus family members.  

PubMed Central

The genetic background of systemic lupus erythematosus (SLE) has been reexamined in a study of the serum of 31 lupus patients and 80 asymptomatic first degree relatives by measuring a common, cross reacting anti-DNA antibody idiotype designated 134, antibodies to poly(ADP-ribose), serum C3, circulating immune complexes, and antinuclear antibodies (ANA). Over 30% of the relatives had raised 134 and anti-poly(ADP-ribose) levels, and 9% had ANA titres greater than 1/20. In contrast, only one relative had a low serum C3 level. These results confirm that immunogenetic abnormalities associated with the production of autoantibodies and particular idiotypes must exist amongst lupus relatives as well as the patients. The production of autoantibodies, however, is not necessarily matched to the clinical expression of SLE.

Dudeney, C; Shoenfeld, Y; Rauch, J; Jones, M; Mackworth Young, C; Tavassoli, M; Shall, S; Isenberg, D A

1986-01-01

222

Targeting of saporin to CD25-positive normal and neoplastic lymphocytes by an anti-saporin/anti-CD25 bispecific monoclonal antibody: in vitro evaluation.  

PubMed Central

This study has been designed to verify the specific toxicity of saporin, a type 1 ribosome-inactivating protein (RIP), with the same activity as ricin A chain, targeted by a bispecific monoclonal antibody (bimAb) recognising both the CD25 antigen and the RIP. The CD25 antigen is expressed by lymphoid populations upon activation and by leukaemias and lymphomas with an activated membrane phenotype (Hodgkin's lymphoma, anaplastic large cell lymphoma, adult T cell leukaemia). The bimAb-saporin mixture was tested on CD25+ targets at different bimAb and saporin concentrations. Saporin, in the presence of a bimAb concentration of 10(-9) M, inhibited protein synthesis by CD25+ neoplastic lymphocytes (L540 and MT2 cell lines) with IC50S (concentrations giving 50% of inhibition) ranging from 8 x 10(-12) M to 3 x 10(-11) M. The saporin-bimAb mixture was also effective in blocking the phytohaemagglutinin-driven proliferation of normal lymphocytes, whereas it displayed the same level of toxicity exerted by saporin alone on an irrelevant CD25-negative cell line (EBV-infected B lymphoblastoid cell line). From these results it is possible to envisage a clinical use of this bimAb as a cytotoxic agent for CD25+ leukaemias and lymphomas, as well as an immunosuppressive agent for severe immune disorders such as graft-vs-host disease (GVHD) and transplanted organ rejection.

Tazzari, P. L.; Zhang, S.; Chen, Q.; Sforzini, S.; Bolognesi, A.; Stirpe, F.; Xie, H.; Moretta, A.; Ferrini, S.

1993-01-01

223

Engineering antibodies by yeast display.  

PubMed

Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering. PMID:22450168

Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

2012-10-15

224

Dynamic adhesion of CD8-positive cells to antibody-coated surfaces: the initial step is independent of microfilaments and intracellular domains of cell-binding molecules  

PubMed Central

Cell adhesion is a multistep, metabolically active process usually requiring several minutes or even hours to complete. This results in the formation of strong bonds that cannot be ruptured by mechanical forces encountered by living cells in their natural environment. However, the first seconds after contact formation are much more sensitive to external conditions and may be the critical step of adhesion. This step is very difficult to monitor without disturbing the observed system. We addressed this problem by studying the interaction between anti-CD8-coated or control surfaces and murine lymphoid cell lines bearing wild-type CD8 molecules, or genetically engineered molecules bearing extracellular CD8 domains and transmembranar and intracytoplasmic domains of class I histocompatibility molecules, or with extensive deletion of intracytoplasmic domains. We used a new method that consisted of monitoring the motion of cells driven along adhesive surfaces by a hydrodynamic force weaker than the reported strength of single ligand-receptor bonds, but sufficient to make free cells move with an easily detectable velocity of several micrometers per second. Cells exhibited short-term (< or = 0.5 s) adhesions to the surface with a frequency of about one event per 30-s period of contact. These events did not require specific antigen-antibody bonds. However, when anti-CD8 were present, strong adhesion was achieved within < 1 s, since most arrests were longer than a standard observation period of 1 min. This bond strengthening was not affected by cytochalasin, and it did not require intact intracellular domains on binding molecules. It is concluded that the initial step in strong adhesion may be viewed as a passive, diffusion-driven formation of a new specific bonds.

1994-01-01

225

DRESS syndrome with fatal results induced by sodium valproate in a patient with brucellosis and a positive cytoplasmic antineutrophilic cytoplasmic antibody test result  

Microsoft Academic Search

DRESS syndrome is a life-threatening adverse reaction characterized by skin rashes, fever, leukocytosis with eosinophilia\\u000a or atypical lymphocytosis, lymph node enlargement, and liver or renal dysfunctions. DRESS syndrome related to valproic acid\\u000a use is very rarely observed. We present a case of DRESS syndrome induced by sodium valproate, which developed and progressed\\u000a fatally in a brucellosis patient with a positive

Serkan Cerrah; Ayse Albayrak; Hakan Dursun; Rahsan Yildirim; Abdullah Uyanik

226

In vitro Activity of Monoclonal and Recombinant Yeast Killer Toxin-like Antibodies Against Antibiotic-resistant Gram-positive Cocci  

Microsoft Academic Search

Background: Monoclonal (mAbKT) and recom- binant single-chain (scFvKT) anti-idiotypic anti- bodies were produced to represent the internal image of a yeast killer toxin (KT) characterized by a wide spectrum of antimicrobial activity, including Gram-positive cocci. Pathogenic eukaryotic and prokaryotic microorganisms, such as Candida albi- cans, Pneumocystis carinii, and a multidrug-resistant strain of Mycobacterium tuberculosis, presenting spe- cific, although yet undefined,

S. Conti; W. Magliani; S. Arseni; E. Dieci; A. Salati; P. E. Varaldo; L. Polonelli

2000-01-01

227

Low incidence of positive smooth muscle antibody and high incidence of isolated IgM elevation in Chinese patients with autoimmune hepatitis and primary biliary cirrhosis overlap syndrome: a retrospective study  

PubMed Central

Background Up to now, few data are available regarding the clinical characteristics of autoimmune hepatitis and primary biliary cirrhosis overlap syndrome. The study was to investigate and analyze the prevalent and clinical features of Chinese patients with this disease. Methods Clinical data on patients diagnosed as autoimmune hepatitis and primary biliary cirrhosis overlap syndrome in our hospital from January 2001 to December 2006 were collected and analyzed. Results Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis accounted for 10.33% of patients with autoimmune liver diseases during the past six years. For these patients with overlap syndrome, xanthochromia, lethargy and anorexia were the predominant complaints; a low incidence (14/146) of smooth muscle antibody positivity and a high incidence (37/89) of isolated IgM elevation were the main serological characteristics. Conclusions Overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis was not rare in Chinese patients with clinical manifests of autoimmune liver diseases. Overlap of the diseases should not be disregarded when isolated IgM elevation was exhibited, and smooth muscle antibody might have little diagnostic significance in the overlap syndrome. If it was difficult to make a definite diagnosis, liver biopsy was necessary.

2012-01-01

228

[Antiphospholipid antibodies].  

PubMed

The concept of antiphospholipid syndrome(APS) has been widely accepted. Antiphospholipid antibodies originally included anticardiolipin antibodies and lupus anticoagulants as serological marker of APS. However, recent advances have shown that most pathogenic antiphospholipid antibodies are directed to phospholipid binding proteins such as beta 2-glycoprotein I and prothrombin as well as phospholipids. The preliminary classification criteria for definite APS have been advocated as the "Sapporo criteria". Further prospective investigations are required to re-evaluate the clinical significance of so-called antiphospholipid antibodies. PMID:12924247

Kaburaki, Junichi; Kuwana, Masataka; Ikeda, Yasuo

2003-07-01

229

Study of nonstandard auto-antibodies as prognostic markers in auto immune hepatitis in children  

PubMed Central

Background Antibodies to chromatin and soluble liver antigen have been associated with severe form of autoimmune hepatitis and/or poor treatment response and may provide guidance in defining subsets of patients with different disease behaviors. The major clinical limitation of these antibodies is their lower individual occurrence in patients with autoimmune hepatitis. Aim To estimate the value of detection of these non-standard antibodies in autoimmune hepatitis as prognostic markers. Methods Both antibodies were tested by enzyme immunoassay in 20 patients with autoimmune hepatitis. Results Antibodies to soluble liver antigen were not detected in any of our patients. On the other hand anti chromatin antibodies were present in 50% (10/20). Antibodies to chromatin occurred more commonly in females than males (8/14 versus 2/6). Of the 14 patients who relapsed 8(57%) had antichromatin antibodies while they were present in only 2 out of 6(33.3%) non relapsers. Antichromatin antibodies were found more in patients with antinuclear (3/4) and anti smooth muscle antibodies (9/13) more than in those with liver kidney microsomal antibodies (1/4) and those seronegative (1/4) i.e. they were +ve in patients with type I (8/12(66.6%)) more than those with type II (1/4(25%)) and those seronegative (1/4(25%)). Antibodies to chromatin are associated with high levels of ? globulin but yet with no statistical difference between seropositive and seronegative counterparts (p = 0.65). Conclusion Antibodies to chromatin may be superior than those to soluble liver antigen in predicting relapse and may be useful as prognostic marker. Further studies with larger number of patients and combined testing of more than one antibody will improve the performance parameters of these antibodies and define optimal testing conditions for them before they can be incorporated into management algorithms that project prognosis.

El- Din Elshazly, Lerine B; Youssef, Azza M; Mahmoud, Nermine H; Ibrahim, Mona M

2009-01-01

230

Serum Antibodies Positivity to 12 Helicobacter pylori Virulence Antigens in Patients with Benign or Malignant Gastroduodenal Diseases - Cross-sectional Study  

PubMed Central

Aim To investigate the association of gastric histological and endoscopic findings in patients with Helicobacter pylori (H. pylori), according to presence of seropositivity to 12 bacterial virulence antigens. Methods This is a cross-sectional single-center study of 360 consecutive outpatients referred in the period of one year to upper gastrointestinal endoscopy because of dyspeptic complaints. Patients sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens – p120 (CagA – cytotoxin-associated antigen), p95 (VacA – vacuolating cytotoxin), p67 (FSH – flagellar sheath protein), p66 (UreB – urease enzyme heavy subunit), p57 (HSP homologue – heath shock protein homologue), p54 (flagellin), p33, p30 (OMP – outer membrane protein), p29 (UreA – urease enzyme light subunit), p26, p19, and p17. Upper gastrointestinal endoscopy was performed, endoscopic diagnosis recorded, and 4 mucosal biopsy samples were obtained and assessed according to Updated Sydney protocol. Results The sera of 207 patients were analyzed. Thirty patients had gastric adenocarcinoma, 126 peptic ulcers, and 51 normal finding. p120 (CagA) seropositivity was significantly more often present in patients with higher activity grade in the antrum (P?=?0.025), p30 in patients with greater inflammation in the antrum (P?=?0.025) and the corpus (P?=?0.010), p33 in patients with greater inflammation in the corpus (P?=?0.050), and p19 (OMP) in patients with lower intestinal metaplasia grades in the corpus (P?=?0.025). Seroreactivity to all other bacterial proteins showed no association with the histological status of the stomach mucosa. Except for the seropositivity to protein p95 (VacA), which was more often present in patients with duodenal ulcer (P?=?0.006), there was no difference in seroreactivity to other bacterial proteins and upper gastrointestinal endoscopic findings. Conclusions p120 (CagA), p33, p 30 (OMP), and p19 (OMP) seropositivity was more often present in patients with higher grades of the histological parameters of gastritis and seropositivity to protein p95 (VacA) with endoscopic presence of duodenal ulcer. Histological parameters of gastritis are more associated with bacterial virulence than endoscopic findings.

Filipec Kanizaj, Tajana; Katicic, Miroslava; Presecki, Vladimir; Gasparov, Slavko; Colic Cvrlje, Vesna; Kolaric, Branko; Mrzljak, Anna

2009-01-01

231

Antithyroid microsomal antibody  

MedlinePLUS

Thyroid antimicrosomal antibody; Antimicrosomal antibody; Microsomal antibody; Thyroid peroxidase antibody; TPOAb ... test is done to confirm the cause of thyroid problems, including Hashimoto's thyroiditis . The test may also ...

232

PF4/heparin-antibody complex induces monocyte tissue factor expression and release of tissue factor positive microparticles by activation of Fc?RI  

PubMed Central

Heparin-induced thrombocytopenia (HIT) is a potentially devastating form of drug-induced thrombocytopenia that occurs in patients receiving heparin for prevention or treatment of thrombosis. Patients with HIT develop autoantibodies to the platelet factor 4 (PF4)/heparin complex, which is termed the HIT Ab complex. Despite a decrease in the platelet count, the most feared complication of HIT is thrombosis. The mechanism of thrombosis in HIT remains poorly understood. We investigated the effects of the HIT Ab complex on tissue factor (TF) expression and release of TF-positive microparticles in peripheral blood mononuclear cells and monocytes. To model these effects ex vivo, we used a murine mAb specific for the PF4/heparin complex (KKO), as well as plasma from patients with HIT. We found that the HIT Ab complex induced TF expression in monocytes and the release of TF-positive microparticles. Further, we found that induction of TF is mediated via engagement of the Fc?RI receptor and activation of the MEK1-ERK1/2 signaling pathway. Our data suggest that monocyte TF may contribute to the development of thrombosis in patients with HIT.

Glover, Sam L.; Jonas, William; McEachron, Troy; Pawlinski, Rafal; Arepally, Gowthami M.; Key, Nigel S.; Mackman, Nigel

2012-01-01

233

[IgA antibodies in exogenous allergic alveolitis are more specific than IgG antibodies].  

PubMed

Nineteen sera from patients suffering from extrinsic allergic alveolitis (bird fancier's lung, farmer's lung) and 19 sera from asymptomatic persons demonstrating IgG-antibodies were examined for IgA-antibodies against pigeon serum, Micropolyspora faeni and Aspergillus fumigatus. The IgA-antibodies against pigeon serum and Micropolyspora faeni were less of ten false-positive than the corresponding IgG-antibodies. Hence the IgA-antibodies were more specific than the IgG-antibodies. However, the sensitivity of the IgA-antibodies was lower than that of the IgG-antibodies. On the other hand IgA-antibodies against Aspergillus fumigatus were scarcely more specific than the corresponding IgG-antibodies against pigeon and M. faeni. It would thus seem that IgA-antibodies can supplement the IgG-serodiagnosis of extrinsic allergic alveolitis. PMID:2367456

Sennekamp, J; Rust, M; Kroidl, R; Spyra, M

1990-02-01

234

Reduced IgG anti-small nuclear ribonucleoprotein autoantibody production in systemic lupus erythematosus patients with positive IgM anti-cytomegalovirus antibodies  

PubMed Central

Introduction Systemic lupus erythematosus is characterized by production of autoantibodies to RNA or DNA–protein complexes such as small nuclear ribonucleoproteins (snRNPs). A role of Epstein–Barr virus in the pathogenesis has been suggested. Similar to Epstein–Barr virus, cytomegalovirus (CMV) infects the majority of individuals at a young age and establishes latency with a potential for reactivation. Homology of CMV glycoprotein B (UL55) with the U1snRNP-70 kDa protein (U1–70 k) has been described; however, the role of CMV infection in production of anti-snRNPs is controversial. We investigated the association of CMV serology and autoantibodies in systemic lupus erythematosus. Methods Sixty-one Mexican patients with systemic lupus erythematosus were tested for CMV and Epstein–Barr virus serology (viral capsid antigen, IgG, IgM) and autoantibodies by immunoprecipitation and ELISA (IgG and IgM class, U1RNP/Sm, U1–70 k, P peptide, rheumatoid factor, dsDNA, ?2-glycoprotein I). Results IgG anti-CMV and IgM anti-CMV were positive in 95% (58/61) and 33% (20/61), respectively, and two cases were negative for both. Clinical manifestation and autoantibodies in the IgM anti-CMV(+) group (n = 20) versus the IgM anti-CMV(-)IgG (+) (n = 39) group were compared. Most (19/20) of the IgM anti-CMV(+) cases were IgG anti-CMV(+), consistent with reactivation or reinfection. IgM anti-CMV was unrelated to rheumatoid factor or IgM class autoantibodies and none was positive for IgM anti-Epstein–Barr virus–viral capsid antigen, indicating that this is not simply due to false positive results caused by rheumatoid factor or nonspecific binding by certain IgM. The IgM anti-CMV(+) group has significantly lower levels of IgG anti-U1RNP/Sm and IgG anti-U1–70 k (P = 0.0004 and P = 0.0046, respectively). This finding was also confirmed by immunoprecipitation. Among the IgM anti-CMV(-) subset, anti-Su was associated with anti-U1RNP and anti-Ro (P < 0.05). High levels of IgG anti-CMV were associated with production of lupus-related autoantibodies to RNA or DNA–protein complex (P = 0.0077). Conclusions Our findings suggest a potential role of CMV in regulation of autoantibodies to snRNPs and may provide a unique insight to understand the pathogenesis.

Palafox Sanchez, Claudia Azucena; Satoh, Minoru; Chan, Edward KL; Carcamo, Wendy C; Munoz Valle, Jose Francisco; Orozco Barocio, Gerardo; Oregon Romero, Edith; Navarro Hernandez, Rosa Elena; Salazar Paramo, Mario; Cabral Castaneda, Antonio; Vazquez del Mercado, Monica

2009-01-01

235

Evaluation of assay methods for hepatitis B surface (HBsAg) antigen and its antibody (anti-HBs) in viral hepatitis B (VHB)-HBsAg-positive.  

PubMed

The sensitivity of methods for the detection of HBsAg and its anti-HBs was compared in serial 1200 sera samples from 30 patients with VHB-HBsAg-positive. HBsAg was tested by gel-diffusion (GD), counter-immunoelectrophoresis (CIE), reversed haemogglutination (rHA), redioimmunoassay (RIA), and enzyme immunoassay (EIA). RIA and EIA methods are statistically significantly more sensitive compared with the other methods (P less than 0.0005). By these methods the minimal concentrations of HBsAg in sera can be proved. Although there is no statistically significant difference in the sensitivity between RIA and EIA, the latter is more sensitive if the subtype ay-HBsAg is considered (12 sera samples). In 24 patients the subtype was ay, in two ad, and in four it could not be differentiated. In 70% of patients anti-HBs was proved by RIA and in 10% by CIE, i.e., in 73% and 9% of sera samples, respectively. In 117 sera samples of these patients the sensitivity of RIA and EIA was compared for determination of anti-HBs. No statistically significant difference between the methods for determination of anti-HBs was found (50.42%: 40.17%). No immune response to HBsAg has been observed in 9 cases, but 6 of them have remained permanent carriers of this antigen. PMID:102913

Mudri?, V; Vukovi?, B; Dimi?, E; Borota, R

1978-11-17

236

Positive anti-citrullinated protein antibody status and small joint arthritis are consistent predictors of chronic disease in patients with very early arthritis: results from the NOR-VEAC cohort  

PubMed Central

Introduction The current 1987 American College of Rheumatology (ACR) classification criteria for rheumatoid arthritis (RA) have proven less useful in early arthritis. The objective of this study was to identify and compare predictors of three relevant outcomes of chronic arthritis in a cohort of very early arthritis patients. Methods The Norwegian Very Early Arthritis Cohort (NOR-VEAC) includes adult patients with at least one swollen joint of ?16 weeks' duration. Patients are followed for 2 years with comprehensive clinical and laboratory examinations. Logistic regression analyses were performed to determine independent predictors of three outcomes: persistent synovitis, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and established clinical RA diagnosis within one year. Results Of 384 patients eligible for one year follow-up (56.3% females, mean (SD) age 45.8 (14.7) years, median (IQR) duration of arthritis 31 (10-62) days), 14.4% were anti-CCP2 positive, and 11.2% were IgM RF positive. 98 patients (25.5%) had persistent synovitis, 106 (27.6%) had received DMARD treatment during follow-up, while 68 (17.7%) were diagnosed with RA. Consistent independent predictors across all three outcomes were positive anti-citrullinated protein antibody (ACPA) status (odds ratio (OR) 3.2, 5.6 and 19.3), respectively, and small joint arthritis (proximal interphalangeal joint (PIP), metacarpo-phalangeal joint (MCP), and/or metatarso-phalangeal joint (MTP) joint swelling) (OR 1.9, 3.5, and 3.5, respectively). Conclusions Positive ACPA status and small joint arthritis were consistent predictors of three relevant outcomes of chronic arthritis in very early arthritis patients. This consistency supports DMARD prescription as a valid surrogate endpoint for chronic arthritis. Importantly, this surrogate is used in ongoing efforts to develop new diagnostic criteria for early RA.

2009-01-01

237

Smoking interacts with HLA-DRB1 shared epitope in the development of anti-citrullinated protein antibody-positive rheumatoid arthritis: results from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA)  

PubMed Central

Introduction Rheumatoid arthritis (RA) is a multifactorial autoimmune disease in which genetic and environmental factors interact in the etiology. In this study, we investigated whether smoking and HLA-DRB1 shared-epitope (SE) alleles interact differently in the development of the two major subgroups of rheumatoid arthritis (RA), anti-citrullinated proteins antibody (ACPA)-positive and ACPA-negative disease, in a multiethnic population of Asian descent. Methods A case-control study comprising early diagnosed RA cases was carried out in Malaysia between 2005 and 2009. In total, 1,076 cases and 1,612 matched controls participated in the study. High-resolution HLA-DRB1 genotyping was performed for shared-epitope (SE) alleles. All participants answered a questionnaire on a broad range of issues, including smoking habits. The odds ratio (OR) of developing ACPA-positive and ACPA-negative disease was calculated for smoking and the presence of any SE alleles separately. Potential interaction between smoking history (defined as "ever" and "never" smoking) and HLA-DRB1 SE alleles also was calculated. Results In our multiethnic study, both the SE alleles and smoking were associated with an increased risk of developing ACPA-positive RA (OR SE alleles, 4.7; 95% confidence interval (CI), 3.6 to 6.2; OR smoking, 4.1; 95% CI, 1.9 to 9.2). SE-positive smokers had an odds ratio of ACPA-positive RA of 25.6 (95% CI, 10.4 to 63.4), compared with SE-negative never-smokers. The interaction between smoking and SE alleles was significant (attributable proportion due to interaction (AP) was 0.7 (95% CI, 0.5 to 1.0)). The HLA-DRB1*04:05 SE allele, which is common in Asian populations, but not among Caucasians, was associated with an increased risk of ACPA-positive RA, and this allele also showed signs of interaction with smoking (AP, 0.4; 95% CI, -0.1 to 0.9). Neither smoking nor SE alleles nor their combination was associated with an increased risk of ACPA-negative RA. Conclusions The risk of developing ACPA-positive RA is associated with a strong gene-environment interaction between smoking and HLA-DRB1 SE alleles in a Malaysian multiethnic population of Asian descent. This interaction seems to apply also between smoking and the specific HLA-DRB1*04:05 SE allele, which is common in Asian populations but not in Caucasians.

2012-01-01

238

Isotype profile and clinical relevance of anticardiolipin antibodies in Sj?gren's syndrome.  

PubMed Central

The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear.

Jedryka-Goral, A; Jagiello, P; D'Cruz, D P; Maldykowa, H; Khamashta, M A; Hughes, G R; Swana, G T; Luft, S

1992-01-01

239

Isotype profile and clinical relevance of anticardiolipin antibodies in Sjögren's syndrome.  

PubMed

The purpose of this study was to determine the occurrence and clinical value of anticardiolipin antibodies in patients with Sjögren's syndrome. Thirty one patients with primary Sjögren's syndrome (all women, mean (SD) age 48.3 (11.2) years) and 32 patients with secondary Sjögren's syndrome with rheumatoid arthritis (all women, mean (SD) age 54.9 (11) years) were studied. IgG, IgM, and IgA anticardiolipin antibodies were determined by a standard enzyme linked immunosorbent assay (ELISA) technique. Anticardiolipin antibodies were found in five patients (16%) with primary Sjögren's syndrome and in seven patients (22%) with secondary Sjögren's syndrome. There was no correlation between anticardiolipin antibodies and the clinical features of the antiphospholipid syndrome (thrombotic events, fetal loss, thrombocytopenia) or extraglandular manifestations of Sjögren's syndrome (arthritis, skin lesions, myositis, polyneuropathy, central nervous system disease, pulmonary and renal disease) in either group. Among the various serological features studied, anticardiolipin antibodies correlated with antinuclear antibodies and antibodies to RNP only in patients with primary Sjögren's syndrome. These results indicate that although anticardiolipin antibodies are often found in serum samples from patients with Sjögren's syndrome, their clinical significance remains unclear. PMID:1632664

Jedryka-Goral, A; Jagiello, P; D'Cruz, D P; Maldykowa, H; Khamashta, M A; Hughes, G R; Swana, G T; Luft, S

1992-07-01

240

Antinuclear Antibody, Rheumatoid Factor, and Cyclic-Citrullinated Peptide Tests for Evaluating Musculoskeletal Complaints in Children. Executive Summary. Effective Health Care Program. Comparative Effectiveness Review Number 50.  

National Technical Information Service (NTIS)

Musculoskeletal (MSK) pain is common in children and adolescents, with an estimated prevalence ranging from 2 to 50 percent. MSK pain can affect physical, psychological, and social function and often prompts consultation with a physician. However, MSK pai...

C. Ha D. M. Dryden J. Homik J. E. Ellsworth K. Bond K. O. Wong M. Kirkland

2012-01-01

241

Presence of antibodies against cyclic citrullinated peptides in patients with 'rhupus': a cross-sectional study  

PubMed Central

'Rhupus' is a rare condition sharing features of rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). If rhupus is a distinctive entity, an overlap between RA and SLE or a subset of SLE is currently debated. This study was performed to explore the prevalence of antibodies against cyclic citrullinated peptides (anti-CCP antibodies) in rhupus. Patients meeting American College of Rheumatology criteria for RA, SLE, or both were included. Clinical and radiographic features were recorded and sera were searched for anti-CCP antibodies, rheumatoid factor, antinuclear antibodies, anti-extractable nuclear antigens, and antibodies against double-stranded DNA (anti-dsDNA antibodies). Seven patients for each group were included. Clinical and serological features for RA or SLE were similar between rhupus and RA patients, and between rhupus and SLE patients, respectively. Values for anti-CCP antibodies obtained were significantly (p < 0.05) higher in RA (6/7) and rhupus (4/7) than in SLE patients (0/7) and healthy subjects (0/7). Our data support the possibility that rhupus is an overlap between RA and SLE, because highly specific autoantibodies for RA (anti-CCP) and for SLE (anti-dsDNA and anti-Sm) are detected in coexistence.

Amezcua-Guerra, Luis M; Springall, Rashidi; Marquez-Velasco, Ricardo; Gomez-Garcia, Lorena; Vargas, Angelica; Bojalil, Rafael

2006-01-01

242

Autoantibodies in sera of Thai patients with Plasmodium falciparum infection.  

PubMed Central

Serum from 98 Thai adults infected with Plasmodium falciparum were examined for the presence of autoantibodies. Malarial containing antibodies sera were also revealed positive for anti-nuclear antibodies with fluorescence speckled pattern, anti-smooth muscle antibodies, anti-mitochondria antibodies and rheumatoid factor. There was no detectable antibody to double stranded DNA. There was a significant relationship between high titre of malarial antibody and high frequency of speckled pattern of anti-nuclear factor or anti-nuclear antibodies. By the ELISA technique determination of serum antibodies against an extractable nuclear antigen (ENA) in patients with P. falciparum infection gave 43.8% (43 of 98) positive result. In addition, sera contained malarial antibodies gave positive antibodies to ENA in 50% (49 of 98) by tanned red cell haemagglutination. Among the positive sera with antibodies to ENA, they showed the presence of antibodies to both ribonucleoprotein RNAase sensitive (RNP) and ribonucleoprotein RNAase resistance (Sm). Also both of antibodies exhibited positive staining of speckled pattern of antinuclear factor. This observation indicated that malaria infection induces autoantibodies which were predominantly anti-nuclear antibodies.

Boonpucknavig, S; Ekapanyakul, G

1984-01-01

243

Antibody fragments  

PubMed Central

The antibody molecule is modular and separate domains can be extracted through biochemical or genetic means. It is clear from review of the literature that a wave of novel, antigen-specific molecular forms may soon enter clinical evaluation. This report examines the developmental histories of therapeutics derived from antigen-specific fragments of antibodies produced by recombinant processes. Three general types of fragments were observed, antigen-binding fragments (Fab), single chain variable fragments (scFv) and “third generation” (3G), each representing a successive wave of antibody fragment technology. In parallel, drug developers have explored multi-specificity and conjugation with exogenous functional moieties in all three fragment types. Despite high hopes and an active pipeline, enthusiasm for differentiating performance of fragments should, perhaps, be tempered as there are yet few data that suggest these molecules have distinct clinical properties due only to their size.

2010-01-01

244

Radioimmunoguided surgery using monoclonal antibody  

SciTech Connect

The potential proficiency of radioimmunoguided surgery in the intraoperative detection of tumors was assessed using labeled monoclonal antibody B72.3 in 66 patients with tissue-proved tumor. Monoclonal antibody B72.3 was injected 5 to 42 days preoperatively, and the hand-held gamma-detecting probe was used intraoperatively to detect the presence of tumor. Intraoperative probe counts of less than 20 every 2 seconds, or tumor-to-adjacent normal tissue ratios less than 2:1 were considered negative (system failure). Positive probe counts were detected in 5 of 6 patients with primary colon cancer (83 percent), in 31 of 39 patients with recurrent colon cancer (79 percent), in 4 of 5 patients with gastric cancer (80 percent), in 3 of 8 patients with breast cancer (37.5 percent), and in 4 of 8 patients with ovarian cancer (50 percent) undergoing second-look procedures. Additional patients in each group were scored as borderline positive. Overall, radioimmunoguided surgery using B72.3 identified tumors in 47 patients (71.2 percent), bordered on positive in 6 patients (9.1 percent), and failed to identify tumor in 13 patients (19.7 percent). Improved selection of patients for antigen-positive tumors, the use of higher affinity second-generation antibodies, alternate routes of antibody administration, alternate radionuclides, and more sophisticatedly bioengineered antibodies and antibody combinations should all lead to improvements in radioimmunoguided surgery.

Martin, E.W. Jr.; Mojzisik, C.M.; Hinkle, G.H. Jr.; Sampsel, J.; Siddiqi, M.A.; Tuttle, S.E.; Sickle-Santanello, B.; Colcher, D.; Thurston, M.O.; Bell, J.G.

1988-11-01

245

Introduction to Antibodies  

NSDL National Science Digital Library

This site contains a thorough overview of the fundamentals of antibodies. The site starts with an introduction to antigens and antibodies, antibody production and titer including practical information.

2011-02-14

246

Auto-Antibodies and Their Association with Clinical Findings in Women Diagnosed with Microscopic Colitis  

PubMed Central

Background Microscopic colitis (MC) is a disease manifested by diarrhoea and is divided into collagenous and lymphocytic colitis. The aetiology is unknown, but auto-immunity is suggested. Auto-antibodies have been only rarely examined in this entity. The aim of the study was to examine the prevalence of auto-antibodies, and to examine associations between the presence of antibodies and clinical findings. Methods and Findings Women with MC verified by biopsy and younger than 73 years, at any Department of Gastroenterology, in the district of Skåne, between 2002 and 2010 were invited to participate in this study. The patients were asked to complete both a questionnaire describing their medical history and the Gastrointestinal Symptom Rating Scale (GSRS). Blood samples were collected. Anti-nuclear antibodies (ANA), anti-neutrophil cytoplasmic antibodies (ANCA), anti-Saccharomyces cerevisiae antibodies (ASCA), and antibodies against glutamic acid decarboxylase (anti-GAD), islet antigens-like insulin 2 (anti-IA2), thyroid peroxidase (anti-TPO), and thyrotropin receptor (TRAK) were analysed. Of 240 women identified, 133 were finally included in the study, median age 63 (59–67) years. Apart from the MC diagnosis, 52% also suffered from irritable bowel syndrome, 31% from hypertension and 31% from allergy. The prevalence of ANA (14%), ASCA IgG (13%), and anti-TPO antibodies (14%) for these patients was slightly higher than for the general population, and were found together with other concomitant diseases. Patients had more of all gastrointestinal symptoms compared with norm values, irrespective of antibody expression. Conclusions Women with MC have a slightly increased prevalence of some auto-antibodies. These antibodies are not associated with symptoms, but are expressed in patients with concomitant diseases, obscuring the pathophysiology and clinical picture of MC.

Ohlsson, Bodil

2013-01-01

247

ANTIBODY FORMATION  

PubMed Central

Injection of a sufficient dose of bacteriophage ?X 174 into guinea pigs results in the formation of rapidly sedimenting antibody molecules (19S), and later, slowly sedimenting molecules (7S). Above a threshold dose of antigen, the relative rate of 19S formation is maximal and dose-independent; below this dose, slower relative rates are obtained. The time for doubling the serum 19S level is as short as 6 to 8 hours, suggesting that the absolute rate of antibody formation per cell is increasing in addition to proliferation of antibody-producing cells. Synthesis of 19S after injection of 1010 ?X virtually ceases at 10 days after which 19S antibody activity disappears from the circulation with a half-life of approximately 24 hours. A second injection of ?X on day 5 or 9 prolongs 19S synthesis, indicating that antigen not only can regulate the relative rate, but also is essential for continued synthesis of 19S. 19S synthesis is also prolonged in guinea pigs by injection of ?X with endotoxin or by 400 r whole body x-irradiation 24 hours after injection of phage into rabbits. The primary 7S response is not detected until approximately 1 week after immunization and relative rates are antigen-dependent. Primary 7S synthesis can continue for many months and leads to preparation for a secondary antibody response (immunological memory) during which only 7S is detected. In contrast, in animals that form precipitating 19S without detectable 7S, a second injection of phage 1 month later results in a second 19S response which closely resembles the first. These findings have led to the suggestion that formation of 19S does not lead to persisting immunological memory.

Uhr, Jonathan W.; Finkelstein, Martin S.

1963-01-01

248

Recently Added Antibodies  

Cancer.gov

Reagents Data Portal AntibodiesNCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit. Print

249

Trifunctional antibody ertumaxomab  

PubMed Central

Background: The trifunctional antibody ertumaxomab bivalently targets the human epidermal growth factor receptor 2 (Her2) on epithelial (tumor) cells and the T cell specific CD3 antigen, and its Fc region is selectively recognized by Fc? type I/III receptor-positive immune cells. As a trifunctional immunoglobulin, ertumaxomab therefore not only targets Her2 on cancer cells, but also triggers immunological effector mechanisms mediated by T and accessory cells (e.g., macrophages, dendritic cells, natural killer cells). Whether molecular effects, however, might contribute to the cellular antitumor efficiency of ertumaxomab are largely unknown. Methods: Potential molecular effects of ertumaxomab on Her2-overexpressing BT474 and SK-BR-3 breast cancer cells were evaluated. The dissociation constant Kd of ertumaxomab was calculated from titration curves that were recorded by flow cytometry. Treatment-induced changes in Her2 homodimerization were determined by flow cytometric fluorescence resonance energy transfer measurements on a cell-by-cell basis. Potential activation / deactivation of Her2, ERK1/2, AKT and STAT3 were analyzed by western blotting, Immunochemistry and immunofluorescent cell staining. Results: The Kd of ertumaxomab for Her2-binding was determined at 265 nM and the ertumaxomab binding epitope was found to not overlap with that of the therapeutic anti-Her2 monoclonal antibodies trastuzumab and pertuzumab. Ertumaxomab caused an increase in Her2 phosphorylation at higher antibody concentrations, but changed neither the rate of Her2-homodimerization /-phosphorylation nor the activation state of key downstream signaling proteins analyzed. Conclusions: The unique mode of action of ertumaxomab, which relies more on activation of immune-mediated mechanisms against tumor cells compared with currently available therapeutic antibodies for breast cancer treatment, suggests that modular or sequential treatment with the trifunctional bivalent antibody might complement the therapeutic activity of other anti-Her2/anti-ErbB receptor reagents.

Diermeier-Daucher, Simone; Ortmann, Olaf; Buchholz, Stefan; Brockhoff, Gero

2012-01-01

250

Evidence in patients with systemic lupus erythematosus of the presence of antibodies against RNA-dependent DNA polymerase of baboon endogenous virus.  

PubMed Central

Immunoglobulin G (IgG) in six out of 30 patients with systemic lupus erythematosus (SLE) strongly inhibited the activity of RNA-dependent DNA polymerase (RDPase) of baboon endogenous virus, M7, while IgG obtained from scleroderma patients, rheumatoid arthritis patients and normal subjects was less reactive. Experiments with anti-human IgG and with IgG F (ab')2-bound immunoaffinity columns indicated that the inhibition of RDPase was antibody-mediated. The RDPase inhibiting activity of SLE IgG was considered not to be due to cross-reactions of anti-nuclear antibodies including anti-DNA, anti-ribonucleoprotein, anti-Sm and anti-SS.B antibodies. SLE IgG preferably inhibited the RDPase activity of baboon endogenous virus and a feline endogenous virus, RD114. These findings support the hypothesis that retrovirus(es) might be involved in SLE.

Okamoto, T; Tamura, T; Takano, T

1983-01-01

251

The antineutrophil antibody in uveitis.  

PubMed Central

Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular single/repeated rather than nonrecurrent uveitis was associated with a positive test. Three groups of patients seem more likely to have positive tests: those with bilateral chronic posterior uveitis; a group with an anterior uveitis which is single/repeated who were younger than 46 at disease onset and had isolated eye disease; and an older group, aged 60 years or more at onset, with single/repeated uveitis and systemic features.

Young, D W

1991-01-01

252

An evaluation of autoimmune antibody testing patterns in a Canadian health region and an evaluation of a laboratory algorithm aimed at reducing unnecessary testing.  

PubMed

Autoantibody tests are often ordered inappropriately. We aimed to evaluate the ordering patterns of these tests in our local health region and to develop a laboratory algorithm aimed at reducing unnecessary tests. Laboratory data including the number and sequence of tests, ordering physician specialties and results for antinuclear (ANA), extractable nuclear antigen (ENA) and anti-double stranded DNA (anti-dsDNA) antibody tests from 2007 to 2009 were evaluated. Based on this information and a clinical consensus meeting, an algorithm was developed and applied retrospectively to 1 year of inpatient laboratory data to simulate potential cost savings. We identified a large volume of these autoantibody tests performed, equating to testing costs of $862,706.72, where less than 17 % of each were positive. Repeated ANA tests were mostly ordered after a previously negative result, and 1 % of patients with negative results changed to ?1:160 on repeat testing. Close to half of all ENA and anti-dsDNA tests that were ordered were done so simultaneously with ANA, suggesting their use as screening tests. This was done more frequently in the inpatient setting. An algorithm was developed where ENA and anti-dsDNA tests would be cancelled if ANA was negative in the same sample. ANA repeated within 1 year would be cancelled and the prior result provided. Application of the algorithm retrospectively simulated a 30 % cost savings. Repeat testing and simultaneous ordering of multiple tests contributed to the excessive ordering of autoantibody tests in our health region. Our proposed algorithm would reduce testing costs and should be accompanied by appropriate educational information for physicians. PMID:23292519

Man, Ada; Shojania, Kam; Phoon, Carmen; Pal, Jason; de Badyn, Monika Hudoba; Pi, David; Lacaille, Diane

2013-05-01

253

Reagents Data Portal Antibodies  

Cancer.gov

NCI announces the release of monoclonal antipeptide antibodies from rabbit for distribution on the antibody portal. There are 60 recently added monoclonal antibodies, with 56 generated from mouse and 4 generated from rabbit.

254

Antibodies to P40.  

National Technical Information Service (NTIS)

The invention relates, in general, to antibodies to p40 (both polyclonal and monoclonal). Additionally, the invention relates to hybridomas which produce monoclonal antibodies to p40 and diagnostic kits comprising antibodies to p40.

T. G. Fanning

1991-01-01

255

Antibody to intermediate filaments of the cytoskeleton.  

PubMed Central

IgM antibodies against cultures of intermediate filaments (IMF) of the cytoskeleton were demonstrated by immunofluorescence in the sera of 94 (80%) of 118 patients with seropositive rheumatoid arthritis. These antibodies reacted with IMF in cultures of both human fetal fibroblasts and laryngeal carcinoma (HEp2) cells. Of 10 patients from whom paired synovial fluids were also available 8 had anti-IMF antibodies in both serum and fluid. In seronegative RA the incidence of anti-IMF was 40%, in ankylosing spondylitis 25%, in osteoarthrosis 16%, and in normal subjects 14%. Only a minority of RA sera positive for anti-IMF antibodies were also positive for smooth muscle antibody. Absorption experiments suggest that in RA anti-IMF is directed at the intermediate filament protein, vimentin. Images

Osung, O A; Chandra, M; Holborow, E J

1982-01-01

256

Analytical performance of the AtheNA MultiLyte® ANA II assay in sera from lupus patients with multiple positive ANAs  

Microsoft Academic Search

The purpose of this study was to evaluate the precision and accuracy of a commercial multiplexed kit for the measurement of\\u000a 9 anti-nuclear antibodies (ANAs; anti-SS\\/A, anti-SS\\/B, anti-Sm, anti-RNP, anti-Jo-1, anti-Scl-70, anti-dsDNA, anti-Centromere\\u000a B, and anti-Histone), and to compare these results to a subset of ANAs measured by enzyme-linked immunosorbent assays (ELISA)\\u000a and immunodiffusion (ID). Sera were obtained from 22

Raymond E. Biagini; Christine G. Parks; Jerome P. Smith; Deborah L. Sammons; Shirley A. Robertson

2007-01-01

257

Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines  

Microsoft Academic Search

Calicheamicin-conjugated humanized anti-CD33 mouse monoclonal antibody, CMA-676, has recently been introduced to clinics as a promising drug to treat patients with acute myeloid leukemia (AML) in relapse. However, the mechanism of action of CMA-676 has not been well elucidated. The cytotoxic effect of CMA-676 on HL60, NOMO-1, NB4, NKM-1, K562, Daudi, and the multidrug-resistant sublines, NOMO-1\\/ADR and NB4\\/MDR, was investigated

K Naito; A Takeshita; K Shigeno; S Nakamura; S Fujisawa; K Shinjo; H Yoshida; K Ohnishi; M Mori; S Terakawa; R Ohno

2000-01-01

258

Subclass restriction and polyclonality of the systemic lupus erythematosus marker antibody anti-Sm.  

PubMed Central

Anti-Sm antibodies are highly specific markers for the diagnosis of systemic lupus erythematosus (SLE). This specificity suggests that the immunoregulation of these autoantibodies would reflect fundamental immune abnormalities in this disorder. As a clue to this immunoregulation, we have investigated the isotype distribution of anti-Sm antibodies by enzyme-linked immunosorbent assays. We have found that the anti-Sm response is markedly restricted to the IgG1 heavy chain isotype. On the other hand, the light chain distribution reflects that in normal serum, while isoelectric focusing analysis fails to show an oligoclonal pattern. The related specificity, anti-ribonucleoprotein, is also restricted to IgG1, while the SLE-specific antibody anti-double-stranded DNA is mostly IgG1 with a lesser contribution by IgG3. These results suggest that antinuclear antibodies that are strongly associated with SLE are produced by a T cell-dependent response, probably driven by antigen. The immunoregulation of the response to several autoantigens may be quite similar. Images

Eisenberg, R A; Dyer, K; Craven, S Y; Fuller, C R; Yount, W J

1985-01-01

259

Renewable, recombinant antibodies to histone post-translational modifications  

PubMed Central

Variability in the quality of antibodies to histone post-translational modifications (PTMs) presents widely recognized hindrance in epigenetics research. Here, by using antibody engineering technologies we produced recombinant antibodies directed to the trimethylated lysine residues of histone H3 with high specificity and affinity and no lot-to-lot variation. These recombinant antibodies performed well in common epigenetics applications, and their high specificity enabled us to identify positive and negative correlations among histone PTMs.

Hattori, Takamitsu; Taft, Joseph M.; Swist, Kalina M.; Luo, Hao; Witt, Heather; Slattery, Matthew; Koide, Akiko; Ruthenburg, Alexander J.; Krajewski, Krzysztof; Strahl, Brian D.; White, Kevin P.; Farnham, Peggy J.; Zhao, Yingming; Koide, Shohei

2013-01-01

260

Antibody Phage Display Technology  

Microsoft Academic Search

In the past decade, the drive to develop completely human antibodies for human therapy has led to the develop- ment of phage display technology. This technology is able to deliver the ultimate in antibody engineering, that is, high-affinity fully human antibodies to any antigen of choice. Here, this application of phage display technology is reviewed, and the many other antibody

Patrick Chames; Hennie R Hoogenboom

2002-01-01

261

Status of antithyroid antibodies in Bangladesh.  

PubMed

To study autoimmunity among thyroid diseases, 397 thyroid patients (age 30 (13) years; M/F 75/322) from two referral centres in Bangladesh and 94 healthy controls (age 30 (13) years; M/F 24/70) were studied for antimicrosomal and antithyroglobulin antibodies. Thyroid patients were clinically grouped as suspected autoimmune thyroid disease (AITD), non-autoimmune, or indeterminate groups (where no decision could be reached). Antimicrosomal antibody was strongly positive in 19.4% and weakly positive in 7.3% of patients but only 4.3% and 2.1% respectively in the controls (chi(2) = 17.852; p = 0.000) whereas strong and weak positivity were 27.2% and 6. 8% in patients compared with 8.5% and 4.3% respectively in the controls (chi(2) = 16.916; p = 0.000) for antithyroglobulin antibody. Antibodies were positive in 63.0% with Hashimoto's thyroiditis, 36.4% with Graves' disease, and 44.7% with atrophic thyroiditis among the autoimmune group. In the non-autoimmune group antibodies were positive in 100% with multinodular hypothyroidism, 46.7% with subacute thyroiditis, 40.0% with suspected iodine deficiency goitre, 31.3% with toxic multinodular goitre, 30.8% with non-toxic solitary nodules, and 19.4% with simple diffuse goitre. None was positive for antimicrosomal antibody without being positive for antithyroglobulin antibody. The two antibodies strongly correlated in both patients (r = 0.977, p = 0.000) and controls (r = 0.986, p = 0.000). About 9% (36/397) of patients were mismatched with the final diagnosis on antibody measurement; most of them had Hashimoto's thyroiditis (33/36). Prevalence of AITD among thyroid patients was 48.36%. Specificity of antimicrosomal and antithyroglobulin antibodies were 93% and 87%. It was concluded that AITD is not uncommon in Bangladesh; antimicrosomal antibody is a useful marker for AITD and unless antibodies are checked, an appreciable number of patients with AITDs will remain undetected. PMID:10824048

Hasanat, M A; Rumi, M A; Alam, M N; Hasan, K N; Salimullah, M; Salam, M A; Fariduddin, M; Mahtab, H; Khan, A K

2000-06-01

262

Status of antithyroid antibodies in Bangladesh  

PubMed Central

To study autoimmunity among thyroid diseases, 397 thyroid patients (age 30 (13) years; M/F 75/322) from two referral centres in Bangladesh and 94 healthy controls (age 30 (13) years; M/F 24/70) were studied for antimicrosomal and antithyroglobulin antibodies. Thyroid patients were clinically grouped as suspected autoimmune thyroid disease (AITD), non-autoimmune, or indeterminate groups (where no decision could be reached). Antimicrosomal antibody was strongly positive in 19.4% and weakly positive in 7.3% of patients but only 4.3% and 2.1% respectively in the controls (?2 = 17.852; p = 0.000) whereas strong and weak positivity were 27.2% and 6.8% in patients compared with 8.5% and 4.3% respectively in the controls (?2 = 16.916; p = 0.000) for antithyroglobulin antibody. Antibodies were positive in 63.0% with Hashimoto's thyroiditis, 36.4% with Graves' disease, and 44.7% with atrophic thyroiditis among the autoimmune group. In the non-autoimmune group antibodies were positive in 100% with multinodular hypothyroidism, 46.7% with subacute thyroiditis, 40.0% with suspected iodine deficiency goitre, 31.3% with toxic multinodular goitre, 30.8% with non-toxic solitary nodules, and 19.4% with simple diffuse goitre. None was positive for antimicrosomal antibody without being positive for antithyroglobulin antibody. The two antibodies strongly correlated in both patients (r = 0.977, p = 0.000) and controls (r = 0.986, p = 0.000). About 9% (36/397) of patients were mismatched with the final diagnosis on antibody measurement; most of them had Hashimoto's thyroiditis (33/36). Prevalence of AITD among thyroid patients was 48.36%. Specificity of antimicrosomal and antithyroglobulin antibodies were 93% and 87%. It was concluded that AITD is not uncommon in Bangladesh; antimicrosomal antibody is a useful marker for AITD and unless antibodies are checked, an appreciable number of patients with AITDs will remain undetected.???Keywords: thyroid autoimmunity; diagnostic dilemma

Hasanat, M; Rumi, M; Alam, M; Hasan, K; Salimullah, M; Salam, M; Fariduddin, M; Mahtab, H.; Khan, A

2000-01-01

263

Antibodies with infinite affinity  

Microsoft Academic Search

Here we report an approach to the design and production of antibody\\/ligand pairs, to achieve functional affinity far greater than avidin\\/biotin. Using fundamental chemical principles, we have developed antibody\\/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody\\/ligand pair as an example, we engineered complementary reactive groups in the antibody binding

Albert J. Chmura; Molly S. Orton; Claude F. Meares

2001-01-01

264

Induction and detection of antibodies to squalene.  

PubMed

An enzyme-linked immunosorbent assay (ELISA) utilizing antigen coated on hydrophobic polyvinyldiene fluoride (PVDF) membranes is described for detecting antibodies that bind to squalene (SQE). Because of the prior lack of availability of validated antibodies to SQE, positive controls for the assay were made by immunization with formulations containing SQE to create monoclonal antibodies (mAbs) that reacted with SQE. Among eight immunogens tested, only two induced detectable murine antibodies to SQE: liposomes containing dimyristoyl phosphatidylcholine, dimyristoyl phosphatidylglycerol, 71% SQE, and lipid A [L(71% SQE+LA)], and, to a much lesser extent, an oil-in-water emulsion containing SQE, Tween 80, Span 85, and lipid A. In each case, lipid A served as an adjuvant, but neither SQE alone, SQE mixed with lipid A, liposomes containing 43% SQE and lipid A, nor several other emulsions containing both SQE and lipid A, induced antibodies that reacted with SQE. Monoclonal antibodies produced after immunizing mice with [L(71% SQE+LA)] served as positive controls for developing the ELISA. Monoclonal antibodies were produced that either recognized SQE alone but did not recognize squalane (SQA, the hydrogenated form of SQE), or that recognized both SQE and SQA. As found previously with other liposomal lipid antigens, liposomes containing lipid A also induced antibodies that reacted with the liposomal phospholipids. However, mAbs were also identified that reacted with SQE on PVDF membranes, but did not recognize either SQA or liposomal phospholipid. The polyclonal antiserum produced by immunizing mice with [L(71% SQE+LA)] therefore contained a mixed population of antibody specificities and, as expected, the ELISA of polyclonal antiserum with PVDF membranes detected antibodies both to SQE and SQA. We conclude that SQE is a weak antigen, but that antibodies that specifically bind to SQE can be readily induced by immunization with [L(71% SQE+LA)] and detected by ELISA with PVDF membranes coated with SQE. PMID:11042279

Matyas, G R; Wassef, N M; Rao, M; Alving, C R

2000-11-01

265

SSA (Ro) antibody in random mother-infant pairs  

Microsoft Academic Search

In a study of the occurrence of detectable antibodies to SS-A and SS-B in 300 randomly selected mother-infant pairs, three (1%) mother-infant pairs were positive for precipitating antibodies to SS-A. No matched pairs were positive for SS-B. Review of the clinical history of the mother-infant pairs with SS-A antibodies failed to reveal evidence of connective tissue disease or the neonatal

M Calmes; B A Bartholomew

1985-01-01

266

Type-specific epitopes targeted by monoclonal antibodies with exceptionally potent neutralizing activities for selected strains of human immunodeficiency virus type 1 map to a common region of the V2 domain of gp120 and differ only at single positions from the clade B consensus sequence.  

PubMed

Only a few monoclonal antibodies (MAbs) have been isolated that recognize conserved sites in human immunodeficiency virus type 1 (HIV-1) Env proteins and possess broad neutralizing activities. Other MAbs directed against targets in various domains of Env have been described that are strongly neutralizing, but they possess limited breadth. One such MAb, 2909, possesses a uniquely potent neutralizing activity specific for a quaternary epitope on SF162 Env that requires the presence of both the V2 and the V3 domains. We now show that replacement of the SF162 V3 sequence with consensus V3 sequences of multiple subtypes led to attenuated but still potent neutralization by 2909 and that the main determinants for the type specificity of 2909 reside in the V2 domain. A substitution at position 160 completely eliminated 2909 reactivity, and mutations at position 167 either attenuated or potentiated neutralization by this antibody. Different substitutions at the same positions in V2 were previously shown to introduce epitopes recognized by MAbs 10/76b and C108g and to allow potent neutralization by these MAbs. Two substitutions at key positions in the V2 domain of JR-FL Env also allowed potent expression of the 2909 epitope, and single substitutions in YU2 V2 were sufficient for expression of the 2909, C108g, and 10/76b epitopes. These results demonstrate that the minimal epitopes for 2909, C108g, and 10/76b differed from that of the clade B consensus sequence only at single positions and suggest that all three MAbs recognize distinct variants of a relatively conserved sequence in V2 that is a particularly sensitive mediator of HIV-1 neutralization. PMID:17121806

Honnen, W J; Krachmarov, C; Kayman, S C; Gorny, M K; Zolla-Pazner, S; Pinter, A

2007-02-01

267

Passive Antibody to Bartonella henselae Protects against Clinical Disease following Homologous Challenge but Does Not Prevent Bacteremia in Cats  

PubMed Central

We challenged cats transfused with anti-Bartonella serum and kittens born to antibody-positive queens with Bartonella henselae to determine the contribution of antibodies to the control of B. henselae in cats. In both experiments, antibody-positive cats were protected from clinical disease but passive antibody to the homologous strain of B. henselae did not prevent bacteremia.

O'Reilly, Kathy L.; Parr, Katy A.; Brown, Tracy P.; Tedder-Ferguson, Belinda; Scholl, Daniel T.

2001-01-01

268

Neutralising antibodies to Akabane virus in ruminants in Cyprus  

Microsoft Academic Search

Neutralising antibodies to Akabane virus, a cause of arthrogryposis and hydranencephaly, were demonstrated in serum samples from 33 sheep, 3 goats and 1 bovine among 285 serum samples collected in south-eastern Cyprus from December 1970 onwards. Twenty-four of the 29 sheep having positive antibodies came from one farm in Liopetri. No positive sera came from animals born after 1969, no

R. F. Sellers; K. A. J. Herniman

1981-01-01

269

Coeliac Disease-Associated Antibodies in Psoriasis  

PubMed Central

Background The possible relationship between psoriasis and coeliac disease (CD) has been attributed to the common pathogenic mechanisms of the two diseases and the presence of antigliadin antibodies in patients has been reported to increase the incidence of CD. Objective The aim of this report was to study CD-associated antibodies serum antigliadin antibody immunoglobulin (Ig)A, IgG, anti-endomysial antibody IgA and anti-transglutaminase antibody IgA and to demonstrate whether there is an increase in the frequency of those markers of CD in patients with psoriasis. Methods Serum antigliadin antibody IgG and IgA, antiendomysial antibody IgA and anti-transglutaminase antibody IgA were studied in 37 (19 males) patients with psoriasis and 50 (23 males) healthy controls. Upper gastrointestinal endoscopy and duodenal biopsies were performed in patients with at least one positive marker. Results Antigliadin IgA was statistically higher in the psoriasis group than in the controls (p<0.05). Serological markers were found positive in 6 patients with psoriasis and 1 person from the control group. Upper gastrointestinal endoscopy was performed in all these persons, with biopsies collected from the duodenum. The diagnosis of CD was reported in only one patient with psoriasis following the pathological examination of the biopsies. Whereas one person of the control group was found to be positive for antigliadin antibody IgA, pathological examination of the duodenal biopsies obtain from this patient were found to be normal. Conclusion Antigliadin IgA prominently increases in patients diagnosed with psoriasis. Patients with psoriasis should be investigated for latent CD and should be followed up.

Akbulut, Sabiye; Gur, Gunes; Topal, Firdevs; Topal, Fatih Esad; Alli, Nuran; Saritas, Ulku

2013-01-01

270

Progranulin antibodies in autoimmune diseases.  

PubMed

Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

2013-05-01

271

Antibody Blood Tests  

MedlinePLUS

... CeliacDisease.net People with celiac disease who eat gluten have higher than normal levels of certain antibodies ... rye and barley that are generically known as “gluten.” Find Out For Sure Antibody tests are only ...

272

Novel nuclear autoantigen with splicing factor motifs identified with antibody from hepatocellular carcinoma.  

PubMed Central

A patient with liver cirrhosis who progressed to hepatocellular carcinoma was found to develop novel antinuclear antibodies. The serum was used to isolate full-length cDNA clones encoding related proteins of 530 amino acids (representative clone HCC1.4) and 524 amino acids (representative clone HCC1.3). Affinity-purified antibodies eluted from recombinant proteins recognized a 64-kD nuclear protein in Western blotting and decorated the nucleoplasm in a speckled-network fashion in immunofluorescence, colocalizing with antibodies to pre-mRNA splicing factor SC35 and uridine-rich small nuclear RNAs. The deduced amino acid sequence contained an arginine/serine-rich (RS) domain and three-ribonucleoprotein consensus sequence domains, two classes of motifs present in several splicing factors. A repeating octapeptide of Arg-Ser-Arg-Ser-Arg(Lys)-Glu(Asp)-Arg-Lys(Arg) was present in RS region of HCC1. This octapeptide sequence called RS-ERK motif was also found in splicing factors U2AF 35- and 65-kD proteins and 70-kD U1 small nuclear ribonucleoprotein. The molecular features and immunolocalization data suggest that the HCC1 autoantigen may be associated with splicing activities and are consistent with observations that autoantibody responses frequently target molecules involved in important cellular biosynthetic functions. Images

Imai, H; Chan, E K; Kiyosawa, K; Fu, X D; Tan, E M

1993-01-01

273

Schistosome Infection Intensity Is Inversely Related to Auto-Reactive Antibody Levels  

PubMed Central

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.

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

274

Antibody profiling sensitivity through increased reporter antibody layering  

DOEpatents

A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

Apel, William A; Thompson, Vicki S

2013-02-26

275

Intracellular antibodies for proteomics  

Microsoft Academic Search

The intracellular antibody technology has many applications for proteomics studies.The potential of intracellular antibodies for the systematic study of the proteome has been made possible by the development of new experimental strategies that allow the selection of antibodies under conditions of intracellular expression. The Intracellular Antibody Capture Technology (IACT) is an in vivo two-hybrid-based method originally developed for the selection

Michela Visintin; Giovanni Antonio Meli; Isabella Cannistraci; Antonino Cattaneo

2004-01-01

276

Antibody therapy of cancer  

Microsoft Academic Search

The use of monoclonal antibodies (mAbs) for cancer therapy has achieved considerable success in recent years. Antibody–drug conjugates are powerful new treatment options for lymphomas and solid tumours, and immunomodulatory antibodies have also recently achieved remarkable clinical success. The development of therapeutic antibodies requires a deep understanding of cancer serology, protein-engineering techniques, mechanisms of action and resistance, and the interplay

Jedd D. Wolchok; Lloyd J. Old; Andrew M. Scott

2012-01-01

277

Modeling Antibody Diversity.  

ERIC Educational Resources Information Center

Understanding antibody structure and function is difficult for many students. The rearrangement of constant and variable regions during antibody differentiation can be effectively simulated using a paper model. Describes a hands-on laboratory exercise which allows students to model antibody diversity using readily available resources. (PVD)

Baker, William P.; Moore, Cathy Ronstadt

1998-01-01

278

Antibodies to OPGL  

US Patent & Trademark Office Database

Antibodies that interact with osteoprotegerin ligand (OPGL) are described. Methods of treating osteopenic disorders by administering a pharmaceutically effective amount of antibodies to OPGL are described. Methods of detecting the amount of OPGL in a sample using antibodies to OPGL are described.

2008-04-29

279

[Bispecific antibodies: what future?].  

PubMed

Monoclonal antibodies have emerged as a very successful class of therapeutic agents. In their native format, monoclonal antibodies are monospecific in that they recognize only one epitope, but their Fc domain also binds to FcfR-expressing cells. Attempts to improve the cytotoxicity of antibodies, particularly in the cancer field, have led to the design of bispecific antibodies: this can occur through various strategies, such as quadroma, thioether-linked Fab' gamma fragments or genetic engineering. Such bispecific antibodies have been developped to enhance immunotherapy, by bridging tumor cells and T cells, or radioimmunotherapy by combining bispecific antibodies and radiolabeled bivalent haptens that bind cooperatively to target cells. Multiple further applications can be envisaged such as targeting two different antigens on the same cell, or two epitopes of the same antigen. Although progresses have been slowed by technical constraints, there is little doubt that this class of novel antibodies derivatives will experience a promising development. PMID:20035697

Pèlegrin, André; Robert, Bruno

2009-12-01

280

Method for altering antibody light chain interactions  

DOEpatents

A method for recombinant antibody subunit dimerization including modifying at least one codon of a nucleic acid sequence to replace an amino acid occurring naturally in the antibody with a charged amino acid at a position in the interface segment of the light polypeptide variable region, the charged amino acid having a first polarity; and modifying at least one codon of the nucleic acid sequence to replace an amino acid occurring naturally in the antibody with a charged amino acid at a position in an interface segment of the heavy polypeptide variable region corresponding to a position in the light polypeptide variable region, the charged amino acid having a second polarity opposite the first polarity. Nucleic acid sequences which code for novel light chain proteins, the latter of which are used in conjunction with the inventive method, are also provided.

Stevens, Fred J. (Naperville, IL); Stevens, Priscilla Wilkins (Evanston, IL); Raffen, Rosemarie (Elmhurst, IL); Schiffer, Marianne (Downers Grove, IL)

2002-01-01

281

A prospective analysis of antibodies reacting with pancreatic islet cells in insulin-dependent diabetic children  

Microsoft Academic Search

Summary  Islet cell cytoplasmic and cell surface antibodies along with other autogenic tissue antibodies were determined prospectively from the day of diagnosis of insulin-dependent diabetes in a group of children and adolescents. Prior to the initiation of insulin therapy 30 out of 33 were antibody-positive, 67% having islet cytoplasmic antibodies and 67% islet cell surface antibodies. Among 74 age- and sex-matched

Å. Lernmark; B. Hägglöf; Z. Freedman; J. Irvine; J. Ludvigsson; G. Holmgren

1981-01-01

282

Association of antipituitary antibody and type 2 iodothyronine deiodinase antibody in patients with autoimmune thyroid disease.  

PubMed

Antipituitary antibody (APA) has been reported to be detected in patients with autoimmune thyroid disease. Type 2 iodothyronine deiodinase (D2) is expressed in both pituitary gland and thyroid gland. We studied the association of APA and D2 peptide antibody in patients with autoimmune thyroid disease. Rat pituitary gland homogenate and D2 peptide were used as antigens in the present study. APA and D2 peptide antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in sera obtained from 42 patients with Hashimoto's disease, 26 patients with Graves' disease and 70 healthy control subjects. Moreover, D2 activity precipitation assay was performed in some patients with Hashimoto's disease. APA and D2 peptide antibody were elevated in patients with Hashimoto's disease and patients with Graves' disease, compared with control subjects. APA was positive in 32.4% (22/68), D2 peptide antibody was positive in 26.5% (18/68) of patients with autoimmune thyroid disease. APA was positive in 31.0% (13/42) of patients with Hashimoto's disease and 34.6% (9/26) of patients with Graves' disease. D2 peptide antibody was positive in 26.2% (11/42) of patients with Hashimoto's disease and 26.9% (7/26) of patients with Graves' disease. D2 peptide antibody was correlated with APA in patients with autoimmune thyroid disease. Moreover, precipitation of D2 activity was increased in some patients with Hashimoto's disease including a patient who also had idiopathic diabetes insipidus, and was correlated with D2 peptide antibody. These results suggest that D2 antibody may be associated with APA in patients with autoimmune thyroid disease. PMID:16410660

Nakahara, Rieko; Tsunekawa, Katsuhiko; Yabe, Shigeki; Nara, Misa; Seki, Koji; Kasahara, Takayuki; Ogiwara, Takayuki; Nishino, Michio; Kobayashi, Isao; Murakami, Masami

2005-12-01

283

Nursing Positions  

MedlinePLUS

... breast with your other hand. The Clutch or Football Hold This is also a good position for ... same time may also choose this position. The football hold allows babies to take milk more easily — ...

284

Anticardiolipin antibodies in patients with Behcet's disease.  

PubMed

The aims of this study are to determine anticardiolipin antibodies in patients with Sy Behcet and to determine correlation between the levels of anticardiolipin antibodies in serum in patients with clinic systemic and ocular manifestations. The study was conducted on 11 patients with Behcet disease (group I), and on 11 healthy subjects (group II). Anticardiolipin antibodies -aCL were determined by the standard ELISA method, where 1GPL= 1 microgram/ml IgG aCL and 1 MPL= 1 microgram/ ml IgM, and were considered negative < 10 GPL or MPL, low positive (10-40 GPL and MPL), or high positive (>40 GPL and MPL). In the group of 11 patients with the diagnosis Sy Behcet, 6 of them were (54.5%) with values of anticardiolipin antibodies over 10 positive. In the control group of the healthy examinees aCl were positive in 2 cases (18.2%). There are no statistically significant differences in the presence of systemic clinic characteristics between aCl positive and negative patients. All the patients with SY Behcet in whom anticardiolipn antibodies were found have extremely severe visual damage which is not present in the group of those patients where the values of aCl were low. The difference is statistically significant. The level of anticardiolipin antibodies is increased in the patients with Behcet. There are no statistically significant differences in the presence of systemic clinical characteristics between aCL positive and negative patients. Visual acuity in patients with SY Behcet is statistically significantly much lower in patients who had increased values of aCL. PMID:21342144

Zivkovic, Maja; Zlatanovic, Marko; Zlatanovic, Gordana; Djordjevic-Jocic, Jasmina; Cekic, Sonja

2011-02-01

285

Anti-salivary gland protein 1 antibodies in two patients with Sjogren's syndrome: two case reports  

PubMed Central

Introduction Current diagnostic criteria for Sjogren’s syndrome developed by the American College of Rheumatology include the presence of antinuclear antibodies, rheumatoid factor, anti-Ro or anti-La autoantibodies. The purpose of this report is to describe two patients with biopsy-proven Sjogren’s syndrome lacking these autoantibodies but identified by antibodies to salivary gland protein 1. Diagnosis was delayed until salivary gland tumors developed in these patients because of the lack of the classic autoantibodies. This report emphasizes the existence of patients with primary Sjogren’s syndrome who lack autoantibodies anti-Ro or anti-La and may therefore be misdiagnosed. Antibodies to salivary gland protein 1 identify some of these patients. Case presentation Two patients are described and were seen in the autoimmune disease clinics of the State University of New York (SUNY) at the Buffalo School of Medicine. In both patients, chronic dry mouth and dry eye had been dismissed as idiopathic because test results for autoantibodies anti-Ro and anti-La were negative. Both patients had swelling of major salivary glands that prompted biopsies. Biopsies of major salivary glands from both cases demonstrated salivary gland tumors and existence of inflammation consistent with Sjogren’s syndrome. Serologic testing revealed antibodies to salivary gland protein 1. Conclusions Patients presenting with classic clinical symptoms of dry mouth and eyes do not always show the current serologic markers of Sjogren’s syndrome, anti-Ro and anti-La. In these cases, investigation for antibodies to salivary gland protein 1 is of importance to make the diagnosis of Sjogren’s syndrome. Early diagnosis of Sjogren’s syndrome is necessary for improved management as well as for vigilance regarding potential complications, such as salivary gland tumors as were seen in the described cases.

2014-01-01

286

Expression studies of catalytic antibodies  

SciTech Connect

We have examined the positive influence of human constant regions on the folding and bacterial expression of active soluble mouse immunoglobulin variable domains derived form a number of catalytic antibodies. Expression yields of eight hybridoma-and myeloma-derived chimeric Fab fragments are compared in both shake flasks and high-density fermentation. In addition the usefulness of this system for the generation of in vivo expression libraries is examined by constructing and expressing combinations of heavy and light chain variable regions that were not selected as a pair during an immune response. A mutagenesis study of one of the recombinant catalytic Fab fragments reveals that single amino acid substitutions can have dramatic effects on the expression yield. This system should be generally applicable to the production of Fab fragments of catalytic and other hybridoma-derived antibodies for crystallographic and structure-function studies. 41 refs., 4 figs., 1 tab.

Ulrich, H.D.; Patten, P.A.; Yang, P.L. [Univ. of California, Berkeley, CA (United States)] [and others

1995-12-05

287

Positional plagiocephaly  

PubMed Central

Cranial asymmetry occurring as a result of forces that deform skull shape in the supine position is known as deformational plagiocephaly. The risk of plagiocephaly may be modified by positioning the baby on alternate days with the head to the right or the left side, and by increasing time spent in the prone position during awake periods. When deformational plagiocephaly is already present, physiotherapy (including positioning equivalent to the preventive positioning, and exercises as needed for torticollis and positional preference) has been shown to be superior to counselling about preventive positioning only. Helmet therapy (moulding therapy) to reduce skull asymmetry has some drawbacks: it is expensive, significantly inconvenient due to the long hours of use per day and associated with skin complications. There is evidence that helmet therapy may increase the initial rate of improvement of asymmetry, but there is no evidence that it improves the final outcome for patients with moderate or severe plagiocephaly.

Cummings, Carl

2011-01-01

288

HIV antibody testing in hospitalized patients.  

PubMed

We retrospectively reviewed the charts of 190 hospitalized patients who had human immunodeficiency virus (HIV) antibody testing at our medical center in 1986 and 1987. From 1986 to 1987, HIV antibody testing increased fourfold based on total hospital discharges. Nine patients (5%) tested positive by enzyme immunoassay and the Western blot method. No risk factor for HIV infection was identified in 30% of cases. Documentation of patients' consent for testing was found in 14% of cases. We conclude that HIV antibody testing of hospitalized patients has increased. However, the indication for testing is often not clear by chart review, and consent for testing is poorly documented in the absence of a formal hospital policy requiring consent before testing. Further physician education and establishment of hospital policies addressing these important aspects of HIV antibody testing are indicated. PMID:2300830

Manian, F A; Rinke, D

1990-01-01

289

Recombinant antibodies to histone post-translational modifications.  

PubMed

Variability in the quality of antibodies to histone post-translational modifications (PTMs) is a widely recognized hindrance in epigenetics research. Here, we produced recombinant antibodies to the trimethylated lysine residues of histone H3 with high specificity and affinity and no lot-to-lot variation. These recombinant antibodies performed well in common epigenetics applications, and enabled us to identify positive and negative correlations among histone PTMs. PMID:23955773

Hattori, Takamitsu; Taft, Joseph M; Swist, Kalina M; Luo, Hao; Witt, Heather; Slattery, Matthew; Koide, Akiko; Ruthenburg, Alexander J; Krajewski, Krzysztof; Strahl, Brian D; White, Kevin P; Farnham, Peggy J; Zhao, Yingming; Koide, Shohei

2013-10-01

290

[Antiganglioside complex antibody].  

PubMed

Antiganglioside antibodies are known to play a pathogenic role in development of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). Recently, antibodies to ganglioside complexes (GSCs) consisting of two different gangliosides were found in some patients with GBS and FS. Some anti-GSC antibodies such as anti-GD1a/GD1b, anti-GM1/GQ1b or anti-GM1/GalNAc-GD1a antibodies correlate with specific clinical features. Anti-GSCs antibodies can be found also in chronic inflammatory demyelinating polyneuropathy and neuropathy associated with IgM monoclonal gammopathy. Latest studies have revealed molecular basis of anti-GSCs antibody-mediated nerve injury. The concept of GSCs will provide new vistas on understanding of pathogenesis of GBS and related autoimmune diseases. PMID:23777091

Hongo, Yu; Kaida, Kenichi

2013-05-01

291

Biobarcodes: Antibodies and Nanosensors  

NSDL National Science Digital Library

In this activity/demo, learners investigate biobarcodes, a nanomedical technology that allows for massively parallel testing that can assist with disease diagnosis. Learners define antibodies and learn how each antibody binds to a unique protein. Learners also discover how biobarcoding uses nanoparticles, antibodies, DNA and magnetism to detect diseases earlier than we could detect before. Learners assemble a jigsaw puzzle that models how biobarcodes work.

Network, Nanoscale I.; Industry, Oregon M.

2014-06-04

292

Antibodies to cholesterol.  

PubMed Central

Cholesterol-dependent complement activation has been proposed as a factor that might influence the pathogenesis of atherosclerosis. Although antibodies to cholesterol conjugates have been reported, cholesterol is widely regarded as a poorly immunogenic substance. Monoclonal IgM complement-fixing antibodies to cholesterol were obtained in the present study after immunizing mice with liposomes containing high amounts of cholesterol (71 mol % relative to phosphatidylcholine) and lipid A as an adjuvant. Clones were selected for the ability of secreted antibodies to react with liposomes containing 71% cholesterol but not with liposomes containing 43% cholesterol. The antibodies also reacted with crystalline cholesterol in a solid-phase enzyme-linked immunosorbent assay. Binding of monoclonal antibodies to the surface of crystalline cholesterol was demonstrated by electron microscopy by utilizing a second antibody (anti-IgM) labeled with colloidal gold. The immunization period required to induce monoclonal antibodies was very short (3 days) and a high fraction of the hybrid cells (at least 70%) were secreting detectable antibodies to cholesterol. The results demonstrate that cholesterol can be a highly immunogenic molecule and that complement-fixing antibodies to cholesterol can be readily obtained. Images

Swartz, G M; Gentry, M K; Amende, L M; Blanchette-Mackie, E J; Alving, C R

1988-01-01

293

Broad neutralization coverage of HIV by multiple highly potent antibodies.  

PubMed

Broadly neutralizing antibodies against highly variable viral pathogens are much sought after to treat or protect against global circulating viruses. Here we probed the neutralizing antibody repertoires of four human immunodeficiency virus (HIV)-infected donors with remarkably broad and potent neutralizing responses and rescued 17 new monoclonal antibodies that neutralize broadly across clades. Many of the new monoclonal antibodies are almost tenfold more potent than the recently described PG9, PG16 and VRC01 broadly neutralizing monoclonal antibodies and 100-fold more potent than the original prototype HIV broadly neutralizing monoclonal antibodies. The monoclonal antibodies largely recapitulate the neutralization breadth found in the corresponding donor serum and many recognize novel epitopes on envelope (Env) glycoprotein gp120, illuminating new targets for vaccine design. Analysis of neutralization by the full complement of anti-HIV broadly neutralizing monoclonal antibodies now available reveals that certain combinations of antibodies should offer markedly more favourable coverage of the enormous diversity of global circulating viruses than others and these combinations might be sought in active or passive immunization regimes. Overall, the isolation of multiple HIV broadly neutralizing monoclonal antibodies from several donors that, in aggregate, provide broad coverage at low concentrations is a highly positive indicator for the eventual design of an effective antibody-based HIV vaccine. PMID:21849977

Walker, Laura M; Huber, Michael; Doores, Katie J; Falkowska, Emilia; Pejchal, Robert; Julien, Jean-Philippe; Wang, Sheng-Kai; Ramos, Alejandra; Chan-Hui, Po-Ying; Moyle, Matthew; Mitcham, Jennifer L; Hammond, Phillip W; Olsen, Ole A; Phung, Pham; Fling, Steven; Wong, Chi-Huey; Phogat, Sanjay; Wrin, Terri; Simek, Melissa D; Koff, Wayne C; Wilson, Ian A; Burton, Dennis R; Poignard, Pascal

2011-09-22

294

Chagas disease and anticardiolipin antibodies in older adults.  

PubMed

Infectious agents have been implicated in the induction of antiphospholipid antibodies and the development of antiphospholipid antibody syndrome. The objective of this study was to evaluate the association of anticardiolipin antibodies with Chagas' disease antibodies. A total of 45 patients, who were positive for Chagas' disease (American Trypanosomiasis) antibodies and had elevated levels of anticardiolipin antibodies, were investigated in a case-control study. Twenty-four of the patients were male and 21 female with ages ranging from 60 to 81 years and with a mean age of 68.3 years. Twenty-three female and 11 male individuals from a senior citizen support group who were apparently healthy formed a control group. Their ages varied from 62 to 80 years with a mean of 68 years. The measurement of anticardiolipin antibodies was performed by means of enzyme-linked immunoabsorbent assay (ELISA) for quantitative measurement of IgG and IgM antibodies against cardiolipins in serum and evaluation of Chagas' disease was confirmed by the Machado Guerreiro test. Statistical analysis was made using Fisher's exact test with a confidence interval of 95% and a p-value <0.05. Elevated levels of anticardiolipin antibodies were detected in 48.8% of the patients and in 26.4% of the control group giving a p-value <0.038 using the Fisher's exact test. Thus, an association between Chagas' disease antibodies and anticardiolipin antibodies was evidenced in this series of patients. PMID:15979738

Pereira de Godoy, Maria Regina; Cação, João Castilho; Pereira de Godoy, José Maria; Brandão, Antonio Carlos; Silva Rossi Souza, Dorotéia

2005-01-01

295

Multiplicity of antibodies in myositis sera.  

PubMed

Serologic studies on 114 patients with polymyositis and dermatomyositis revealed that 89% had either a precipitating antibody to antigens in calf thymus extract or a positive immunofluorescent reaction on HEp-2 cells, a human tissue culture line. Previously, the greatest proportion of polymyositis sera demonstrating positive serologic results (i.e., the proportion of patients' sera forming precipitates with calf thymus extract) was reported to be 60%. Use of the HEp-2 cell as immunofluorescent substrate enabled the detection of antibody in 89 (78%) of the sera, providing the additional probe which demonstrated specific antibody. Nuclear, cytoplasmic, and nucleolar staining are the most common patterns of immunofluorescence. The immunofluorescent patterns and individual precipitin reactions are related to each other and to the clinical syndromes in which they appear. PMID:6386003

Reichlin, M; Arnett, F C

1984-10-01

296

The antibody mining toolbox  

PubMed Central

In vitro selection has been an essential tool in the development of recombinant antibodies against various antigen targets. Deep sequencing has recently been gaining ground as an alternative and valuable method to analyze such antibody selections. The analysis provides a novel and extremely detailed view of selected antibody populations, and allows the identification of specific antibodies using only sequencing data, potentially eliminating the need for expensive and laborious low-throughput screening methods such as enzyme-linked immunosorbant assay. The high cost and the need for bioinformatics experts and powerful computer clusters, however, have limited the general use of deep sequencing in antibody selections. Here, we describe the AbMining ToolBox, an open source software package for the straightforward analysis of antibody libraries sequenced by the three main next generation sequencing platforms (454, Ion Torrent, MiSeq). The ToolBox is able to identify heavy chain CDR3s as effectively as more computationally intense software, and can be easily adapted to analyze other portions of antibody variable genes, as well as the selection outputs of libraries based on different scaffolds. The software runs on all common operating systems (Microsoft Windows, Mac OS X, Linux), on standard personal computers, and sequence analysis of 1–2 million reads can be accomplished in 10–15 min, a fraction of the time of competing software. Use of the ToolBox will allow the average researcher to incorporate deep sequence analysis into routine selections from antibody display libraries.

D'Angelo, Sara; Glanville, Jacob; Ferrara, Fortunato; Naranjo, Leslie; Gleasner, Cheryl D; Shen, Xiaohong; Bradbury, Andrew RM; Kiss, Csaba

2014-01-01

297

Antibodies as effectors.  

PubMed

Antibodies are critical in protection against extracellular microbial pathogens. Although antibodies also play a role in transplant/tumor rejection and in autoimmune disease, this paper focuses on defense against bovine infections. Effector mechanisms of different bovine isotypes, subisotypes and allotypes are discussed. The importance of antigen specificity is also stressed. PMID:12072231

Corbeil, L B

2002-09-10

298

Antibodies with infinite affinity.  

PubMed

Here we report an approach to the design and production of antibody/ligand pairs, to achieve functional affinity far greater than avidin/biotin. Using fundamental chemical principles, we have developed antibody/ligand pairs that retain the binding specificity of the antibody, but do not dissociate. Choosing a structurally characterized antibody/ligand pair as an example, we engineered complementary reactive groups in the antibody binding pocket and the ligand, so that they would be in close proximity in the antibody/ligand complex. Cross-reactions with other molecules in the medium are averted because of the low reactivity of these groups; however, in the antibody/ligand complex the effective local concentrations of the complementary reactive groups are very large, allowing a covalent reaction to link the two together. By eliminating the dissociation of the ligand from the antibody, we have made the affinity functionally infinite. This chemical manipulation of affinity is applicable to other biological binding pairs. PMID:11447282

Chmura, A J; Orton, M S; Meares, C F

2001-07-17

299

Nuclear Positioning  

PubMed Central

SUMMARY The nucleus is the largest organelle and is commonly depicted in the center of the cell. Yet during cell division, migration and differentiation, it frequently moves to an asymmetric position aligned with cell function. We consider the toolbox of proteins that move and anchor the nucleus within the cell and how forces generated by the cytoskeleton are coupled to the nucleus to move it. The significance of proper nuclear positioning is underscored by numerous diseases resulting from genetic alterations in the toolbox proteins. Finally, we discuss how nuclear position may influence cellular organization and signaling pathways.

Gundersen, Gregg G.; Worman, Howard J.

2013-01-01

300

Antibodies for biodefense  

PubMed Central

Potential bioweapons are biological agents (bacteria, viruses and toxins) at risk of intentional dissemination. Biodefense, defined as development of therapeutics and vaccines against these agents, has seen an increase, particularly in the US, following the 2001 anthrax attack. This review focuses on recombinant antibodies and polyclonal antibodies for biodefense that have been accepted for clinical use. These antibodies aim to protect against primary potential bioweapons or category A agents as defined by the Centers for Disease Control and Prevention (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox virus and certain others causing viral hemorrhagic fevers) and certain category B agents. Potential for prophylactic use is presented, as well as frequent use of oligoclonal antibodies or synergistic effect with other molecules. Capacities and limitations of antibodies for use in biodefense are discussed, and are generally applicable to the field of infectious diseases.

Froude, Jeffrey W; Stiles, Bradley; Pelat, Thibaut

2011-01-01

301

[Humanized antibodies as therapeutics].  

PubMed

Since 1997, nine humanized antibodies received the approval of the FDA to be used as drugs for the treatment of various diseases including transplant rejections, metastatic breast and colon cancers, leukaemia, non-Hodgkin lymphomas, allergic conditions or multiple sclerosis. This review describes techniques used to engineer these antibodies and presents the recent evolutions of these techniques : SDRs grafting or < abbreviated > CDRs grafting. Based on the illustrative examples of several antibodies, Mylotarg, Herceptin or Xolair, the therapeutic effectiveness of humanized antibodies are underlined and, with the example of Tysabri, the sometimes dramatic adverse effects associated with their clinical use is stressed. In a second part, this review presents some future and realistic avenues to improve the effectiveness of the humanized antibodies, to decrease their immunogenicity and to reduce their cost. PMID:16324646

Bellet, Dominique; Dangles-Marie, Virginie

2005-12-01

302

Red Blood Cell Antibody Identification  

MedlinePLUS

... Antibody ID, RBC; RBC Ab ID Formal name: Red Blood Cell Antibody Identification Related tests: Direct Antiglobulin ... None The Test Sample What is being tested? Red blood cell antibodies are proteins produced by the ...

303

Encephalitozoon cuniculi in rabbits in Germany: prevalence and sensitivity of antibody testing.  

PubMed

The aim of this study was to investigate the prevalence of Encephalitozoon cuniculi antibodies in healthy and diseased rabbits in Germany. Age and gender dependencies were taken into consideration. The sensitivity of the E cuniculi antibody test and its relevance for the diagnosis of E cuniculi infection in rabbits was also examined. A total of 773 healthy and diseased rabbits were tested for E cuniculi antibodies (indirect immune fluorescence antibody test (IFAT) or carbon immunoassay (CIA). No differences between diseased and healthy rabbits were observed with regard to gender, but diseased rabbits were significantly older (P>0.001). Forty-three percent (336/773) of all rabbits were positive for E cuniculi antibodies. Of the diseased rabbits, 48 per cent (266/555) were positive for E cuniculi antibodies. While 96 per cent (91/95) of the rabbits with histopathologically or PCR confirmed encephalitozoonosis were E cuniculi antibody-positive, only 60 per cent (144/241) of the rabbits suspected of E cuniculi infection were antibody-positive. Of the healthy rabbits, 18 per cent (39/218) were positive for E cuniculi antibodies. Diseased rabbits were almost three times more likely to be E cuniculi antibody-positive than healthy ones (P>0.001; relative risk (RR): 2.68; 95% CI 1.99 to 3.61). The sensitivity of the E cuniculi antibody test was 96 per cent. PMID:24570403

Hein, J; Flock, U; Sauter-Louis, C; Hartmann, K

2014-04-01

304

Positive Proof.  

ERIC Educational Resources Information Center

Presents experiments which show that in electrostatics there are logical reasons for describing charged materials as positive or negative. Indicates that static and current electricity are not separate areas of physics. Diagrams of experiments and circuits are included. (RT)

Auty, Geoffrey

1988-01-01

305

Positive Computing  

Microsoft Academic Search

\\u000a In his opening speech at the International Positive Psychology Association (IPPA) Conference in June 2009, Martin Seligman,\\u000a founder of Positive Psychology, formulated a formidable challenge: By the year 2051, 51% of the world population should be\\u000a flourishing. This is an ambitious goal given that even in the richer, “happier” Western world only 2 in 10 people are considered\\u000a to be

Tomas Sander

306

Antibody discovery: sourcing of monoclonal antibody variable domains.  

PubMed

Historically, antibody variable domains for therapeutic antibodies have been sourced primarily from the mouse IgG repertoire, and typically either chimerized or humanized. More recently, human antibodies from transgenic mice producing human IgG, phage display libraries, and directly from human B lymphocytes have been used more broadly as sources of antibody variable domains for therapeutic antibodies. Of the total 36 antibodies approved by major maket regulatory agencies, the variable domain sequences of 26 originate from the mouse. Of these, four are marketed as murine antibodies (of which one is a mouse-rat hybrid IgG antibody), six are mouse-human chimeric antibodies, and 16 are humanized. Ten marketed antibodies have originated from human antibody genes, three isolated from phage libraries of human antibody genes and seven from transgenic mice producing human antibodies. Five antibodies currently in clinical trials have been sourced from camelids, as well as two from non-human primates, one from rat, and one from rabbit. Additional sources of antibody variable domains that may soon find their way into the clinic are potential antibodies from sharks and chickens. Finally, the various methods for retrieval of antibodies from humans, mouse and other sources, including various display technologies and amplification directly from B cells, are described. PMID:24168292

Strohl, William R

2014-03-01

307

Tumor localization by combinations of monoclonal antibodies in a new human colon carcinoma cell line (LIM1899)  

SciTech Connect

One of the problems of in vivo diagnosis and therapy of tumors with monoclonal antibodies is their heterogeneity with respect to antigen expression, with some cells expressing no antigen and others being weakly or strongly positive. Selected mixtures of antibodies to different antigens are therefore likely to react with more cells than single antibodies and be more effective for imaging and therapy. With this in mind, we have examined a new human colon cancer cell line (LIM1899) which has a heterogeneous expression of several cell surface molecules: by flow cytometry 38% were carcinoembryonic antigen positive; 64%, human milk fat globule positive, and 73%, CD46 positive; 87% of tumor cells bound a mixture of all three antibodies in vitro. Some blocking of the binding of anti-human milk fat globule antibody by the anti-CD46 antibody was noted. LIM1899 was established as a xenograft in nude mice and in vivo biodistribution studies performed using antibodies alone or in combination. Mixtures of antibodies clearly showed a higher percentage of injected dose of antibody in the tumor than did single antibodies: one antibody gave 10%; two together, 17 to 21%; and all three together gave 29% of the injected dose in the tumor. Tumor:blood ratios were also superior for combinations of antibodies, provided that low doses of the antibodies were used; at higher doses the effect was lost. The study demonstrates that combinations of antibodies are better than single antibodies for localization, provided that the dose used is carefully selected.

Andrew, S.M.; Teh, J.G.; Johnstone, R.W.; Russell, S.M.; Whitehead, R.H.; McKenzie, I.F.; Pietersz, G.A. (Univ. of Melbourne, Parkville, Victoria (Australia))

1990-09-01

308

Generation of neutralising antibodies against porcine endogenous retroviruses (PERVs)  

SciTech Connect

Antibodies neutralising porcine endogenous retroviruses (PERVs) were induced in different animal species by immunisation with the transmembrane envelope protein p15E. These antibodies recognised epitopes, designated E1, in the fusion peptide proximal region (FPPR) of p15E, and E2 in the membrane proximal external region (MPER). E2 is localised in a position similar to that of an epitope in the transmembrane envelope protein gp41 of the human immunodeficiency virus-1 (HIV-1), recognised by the monoclonal antibody 4E10 that is broadly neutralising. To detect neutralising antibodies specific for PERV, a novel assay was developed, which is based on quantification of provirus integration by real-time PCR. In addition, for the first time, highly effective neutralising antibodies were obtained by immunisation with the surface envelope protein of PERV. These data indicate that neutralising antibodies can be induced by immunisation with both envelope proteins.

Kaulitz, Danny; Fiebig, Uwe; Eschricht, Magdalena; Wurzbacher, Christian; Kurth, Reinhard; Denner, Joachim, E-mail: DennerJ@rki.d

2011-03-01

309

Class specific antibodies in serodiagnosis of farmer's lung.  

PubMed Central

The aim of the present study was to determine which microbes and which immunoglobulin (Ig) classes should be included in tests to discriminate between patients with farmer's lung and reference persons. The sera of a group of farmer's lung patients and their spouses were measured for IgG, IgA, IgM, and IgE antibodies against a panel of farmer's lung microbes. The concentrations of IgG, IgA, and IgE antibodies were higher in patients compared with their spouses. The patients were generally positive for antibodies of several Ig classes whereas the spouses had only either IgG or IgA antibodies. A test comprising the determinations of IgG antibodies against T vulgaris and IgA antibodies against A fumigatus would correctly group 94% of the cases in the Finnish farming population. The selection of microbes for other environments needs to be determined locally.

Ojanen, T

1992-01-01

310

Usefulness of IgG4 subclass antibodies for diagnosis of human clonorchiasis  

PubMed Central

The present study analyzed serum IgG subclass antibody reaction to major antigenic bands of Clonorchis sinensis to investigate improvement of its serodiagnosis. Of the four subclass antibodies, IgG1 and IgG2 antibodies were produced but not specific, IgG3 antibody was least produced, and IgG4 antibody was prominent and specific. The serum IgG antibody reaction to any of 43-50, 34-37, 26-28, and 8 kDa bands was found in 65.5% of 168 egg positive cases while IgG4 antibody reaction was found in 22.0% of them. The positive rates of IgG and IgG4 antibodies were directly correlated with the intensity of infection. All of the sera from heavily infected cases over EPG 5,000 showed positive reaction for specific IgG and IgG4 antibodies. The specific serum IgG4 antibody disappeared within 6 months after treatment. The bands of 35 kDa and 67 kDa cross-reacted with IgG antibodies but not with IgG4 antibodies in sera of other trematode infections. The present findings suggest that serum IgG4 antibody reaction to 8 kDa band is specific but not sensitive. Any method to increase its sensitivity is required for improved serodiagnosis.

Lee, Mejeong; Sung, Nak-Jin; Cho, Sang Rock; Chai, Jong-Yil; Lee, Soon-Hyung

1999-01-01

311

A serological survey of domestic poultry in the united kingdom for antibody to chicken anaemia agent  

Microsoft Academic Search

A serological survey for antibody to chicken anaemia agent (CAA) was carried out by indirect immunofluorescence. Antibody to CAA was widespread in broiler breeders and in parent and commercial layers in the UK. Antibody to CAA was also detected in five of 11 specific pathogen?free (SPF) chicken flocks tested; positive flocks included those being used for vaccine production or as

M. S. McNulty; T. J. Connor; F. McNeilly; K. S. Kirkpatrick; J. B. McFerran

1988-01-01

312

Antibody production in mice  

PubMed Central

To study the mechanism of antigenic stimulation in the secondary immune response, primed lymphoid cells were stimulated with antigen in various ways in vitro. The effect of antigenic stimulation was assessed by the antibody titres obtained after in vivo culture of primed cells in X-irradiated recipients. Primed cells were much more effectively stimulated by antigen—antibody (Ag—Ab) complex than by free antigen. Primed cells could also be stimulated by spleen or lymph node cells from normal mice which had been exposed to free antigen or Ag—Ab complex in vitro or in vivo and thoroughly washed. Under these conditions, Ag—Ab complex was again much more effective than free antigen. When the cells were incubated with Ag—Ab complex, the dose of antigen bound to the cells was somewhat increased. But this increased binding of antigen could not solely account for the increase in immunogenicity. It is suggested that the ingestion of antigen by macrophages is facilitated by the presence of antibody and that the macrophages mediate the effective immune stimulus to memory cells. The effect of antibody in increasing the immunogenicity of antigen was lost completely when antibody was digested with pepsin. Thus, the Fc portion of antibody seemed to be important for this effect. However, it was demonstrated that antibody does not operate by becoming attached to macrophages as cytophilic antibody, and that complement is not involved in this process. The augmenting mechanism of antibody on the antigenic stimulation mediated by macrophages was discussed. ImagesFIG. 2

Hamaoka, T.; Kitagawa, M.

1971-01-01

313

EQUINE ANTIHAPTEN ANTIBODY  

PubMed Central

Eight antigenically unique immunoglobulins have been identified in purified equine anti-p-azophenyl-?-lactoside (Lac) antibody isolated from a single horse. The Fc fragments of the ?Ga-, ?Gb-, ?Gc-, and -?A-globulins have been shown to possess unique antigenic determinants. Common ?G- and ?A-Fc fragment antigenic determinants, which were absent from the 10S?1- and ?M-globulins, have also been observed. All antibody populations share two antigenically distinct light (B, L) chain variants. The association of anti-Lac antibody with the hapten p-(p-dimethylamino-benzeneazo)-phenyl-?-lactoside has been measured by equilibrium dialysis and by fluorescence quenching. A variation in the affinity of anti-Lac antibody for hapten has been observed. The affinity of antibody was unaltered by enzymatic removal of the Fc fragments by peptic digestion or dissociation of the two combining sites on the papain 3.5S Fab fragments, indicating that the observed heterogeneity of affinities was not a direct function of the heterogeneity in structure of the Fc fragments. Isolated heavy (A, H) chains of ?A-anti-Lac antibody have been shown to have retamed affinity for Lac dye by equilibrium dialysis and by analytical ultracentrifugation, employing a combination of schlieren and absorption optics. The heavy (A, H) chains from two physically separable, antigenically distinct antibody populations, isolated from the same animal and having affinity for the same haptenic determinant, have been found to differ in their amino acid composition. Anti-Lac antibody light (B, L) chains have also been shown to be chemically heterogeneous, and contained populations of polypeptide chains possessing, and populations lacking methionine. The relevance of the observed structural heterogeneity of equine anti-Lac antibody to the problem of defining the mechanism of acquisition of immunological specificity is briefly discussed.

Rockey, John H.

1967-01-01

314

Monoclonal antibody "gold rush".  

PubMed

The market, sales and regulatory approval of new human medicines, during the past few years, indicates increasing number and share of new biologics and emergence of new multibillion dollar molecules. The global sale of monoclonal antibodies in 2006 were $20.6 billion. Remicade had annual sales gain of $1 billion during the past 3 years and five brands had similar increase in 2006. Rituxan with 2006 sales of $4.7 billion was the best selling monoclonal antibody and biological product and the 6th among the top selling medicinal brand. It may be the first biologic and monoclonal antibody to reach $10 billion annual sales in the near future. The strong demand from cancer and arthritis patients has surpassed almost all commercial market research reports and sales forecast. Seven monoclonal antibody brands in 2006 had sales exceeding $1 billion. Humanized or fully human monoclonal antibodies with low immunogenicity, enhanced antigen binding and reduced cellular toxicity provide better clinical efficacy. The higher technical and clinical success rate, overcoming of technical hurdles in large scale manufacturing, low cost of market entry and IND filing, use of fully human and humanized monoclonal antibodies has attracted funds and resources towards R&D. Review of industry research pipeline and sales data during the past 3 years indicate a real paradigm shift in industrial R&D from pharmaceutical to biologics and monoclonal antibodies. The antibody bandwagon has been joined by 200 companies with hundreds of new projects and targets and has attracted billions of dollars in R&D investment, acquisitions and licensing deals leading to the current Monoclonal Antibody Gold Rush. PMID:17691940

Maggon, Krishan

2007-01-01

315

Designing antibodies for oncology.  

PubMed

The past five years have witnessed the emergence of monoclonal antibodies as important therapeutics for cancer treatment. Lower toxicity for antibodies versus small molecules, the potential for increased efficacy by conjugation to radioisotopes and cellular toxins, or the ability to exploit immune cell functions have led to clinical performances on par or superior to conventional drug therapies. This review outlines the various immunoglobulin design strategies currently available, techniques used to reduce Ig antigenicity and toxicity, and points to consider during the manufacture of antibodies for use in clinical oncology. PMID:16408163

Tanner, Jerome E

2005-12-01

316

Position indicator  

DOEpatents

A nuclear reactor system is described in which a position indicator is provided for detecting and indicating the position of a movable element inside a pressure vessel. The movable element may be a valve element or similar device which moves about an axis. Light from a light source is transmitted from a source outside the pressure vessel to a first region inside the pressure vessel in alignment with the axis of the movable element. The light is redirected by a reflector prism to a second region displaced radially from the first region. The reflector prism moves in response to movement of the movable element about its axis such that the second region moves arcuately with respect to the first region. Sensors are arrayed in an arc corresponding to the arc of movement of the second region and signals are transmitted from the sensors to the exterior of the reactor vessel to provide indication of the position of the movable element.

Tanner, David E. (Poway, CA)

1981-01-01

317

Relationship between formaldehyde-related antibodies and cross-reacting anti-N-like antibodies in patients undergoing chronic haemodialysis.  

PubMed

An attempt was made to determine the sequence of events leading to the production of two distinct antibodies in patients with chronic renal failure who regularly undergo haemodialysis with formaldehyde-resterilizable dialysis units by Multipoint (UK) or Cordis (USA). A distinct pattern emerged-namely, the production of anti-formaldehyde red cells started about six months after the beginning of haemodialysis treatment. Only when the titre of these antibodies reached 64 or 128 another, apparently cross-reacting, antibody appeared which reacted like an anti-N antibody. A strong direct antiglobulin reaction was found to be positive for formalin-treated red cells after five minutes' contact with specific antibody, indicating a high affinity of the antibody fo the formalin-altered red cell. PMID:7053234

Sharon, R

1981-01-01

318

Lyme disease antibody  

MedlinePLUS

Lyme disease serology; ELISA for Lyme disease; Western blot for Lyme disease ... see: Venipuncture . A laboratory specialist will look for Lyme disease antibodies in the blood sample using the ELISA ...

319

Future of antibody purification.  

PubMed

Antibody purification seems to be safely ensconced in a platform, now well-established by way of multiple commercialized antibody processes. However, natural evolution compels us to peer into the future. This is driven not only by a large, projected increase in the number of antibody therapies, but also by dramatic improvements in upstream productivity, and process economics. Although disruptive technologies have yet escaped downstream processes, evolution of the so-called platform is already evident in antibody processes in late-stage development. Here we perform a wide survey of technologies that are competing to be part of that platform, and provide our [inherently dangerous] assessment of those that have the most promise. PMID:17134947

Low, Duncan; O'Leary, Rhona; Pujar, Narahari S

2007-03-15

320

Designing antibodies for oncology  

Microsoft Academic Search

Summary  The past five years have witnessed the emergence of monoclonal antibodies as important therapeutics for cancer treatment.\\u000a Lower toxicity for antibodies versus small molecules, the potential for increased efficacy by conjugation to radioisotopes\\u000a and cellular toxins, or the ability to exploit immune cell functions have led to clinical performances on par or superior\\u000a to conventional drug therapies. This review outlines

Jerome E. Tanner

2005-01-01

321

Monoclonal antibodies as a tool for phylogenetic studies of major histocompatibility antigens and ? 2 -microglobulin  

Microsoft Academic Search

The cross-reactivity of several monoclonal antibodies recognizing monomorphic determinants of human HLA-A, B, C, and DR antigens and human ß2-microglobulin (ß2m) has been studied on peripheral blood leukocytes in 24 different species. An monoclonal HLA-A-, B-, and C-specific antibody and four monoclonal HLA-DR-specific antibodies cross-reacted with cells from all the primate species tested. Furthermore, antibodies HLA-DR-specific were positive with peripheral

Jean-Luc Teillaud; Denis Crevat; Patrick Chardon; Jorge Kalil; Cécile Goujet-Zalc; Guy Mahouy; Marcel Vaiman; Marc Fellous; Donald Piou

1982-01-01

322

The presence of thyrogastric antibodies in first degree relatives of type 1 diabetic patients is associated with age and proband antibody status.  

PubMed

A quarter of type 1 diabetic patients have thyrogastric autoantibodies (thyroid peroxidase and gastric parietal cell antibodies). Clinical, immune, and genetic risk factors help predict antibody status. First degree relatives of these patients may also frequently exhibit these antibodies. We assessed the prevalence of thyrogastric antibodies and dysfunction in first degree relatives in relation to age, gender, human leukocyte antigen-DQ type, beta-cell antibody (islet cell, glutamic acid decarboxylase-65, and tyrosine phosphatase antibodies), and proband thyrogastric antibody status. Sera from 272 type 1 diabetic patients (116 men and 156 women; mean age, 27 +/- 18 yr; duration, 10 +/- 9 y), 397 first degree relatives (192 men and 205 women; parents/siblings/offspring, 48/222/127; age, 22 +/- 10 yr), and 100 healthy controls were tested for islet cell antibodies and gastric parietal cell antibodies by indirect immunofluorescence and for tyrosine phosphatase, glutamic acid decarboxylase-65, and thyroid peroxidase antibodies by radiobinding assays. Glutamic acid decarboxylase-65 antibodies were present in 68% and 5%, islet cell antibodies were present in 36% and 2.5%, tyrosine phosphatase antibodies were present in 45% and 0.5%, thyroid peroxidase antibodies were present in 21% and 4.5%, and gastric parietal cell antibodies were present in 18% and 11% of diabetic patients and relatives, respectively. The presence of thyroid peroxidase antibodies in relatives was determined by age (beta = 0.22; P = 0.0001) and proband thyroid peroxidase antibodies status (beta = -2.6; P = 0.002; odds ratio = 11.1). Gastric parietal cell antibody positivity in relatives was associated with age (beta = 0.04; P = 0.026). Gastric parietal cell antibody-positive compared with gastric parietal cell antibody-negative relatives were more likely to have gastric parietal cell antibody-positive probands (P = 0.01; odds ratio = 3.0). beta-Cell antibody status and human leukocyte antigen-DQ type did not influence thyrogastric antibody status in relatives. (Sub)clinical dysthyroidism was found in 3%, iron deficiency anemia was present in 12% (26% gastric parietal cell antibody-positive and 9% gastric parietal cell antibody-negative subjects; P = 0.009), and pernicious anemia was found in 0.5% (5% gastric parietal cell antibody-positive and 0% gastric parietal cell antibody-negative subjects; P = 0.012) of relatives. They had less thyroid dysfunction (P < 0.0001) and pernicious anemia (P = 0.018) than diabetic probands. In conclusion, thyrogastric antibodies and dysfunction are more prevalent in type 1 diabetic patients than in first degree relatives. The presence of these antibodies in relatives is associated with age and proband antibody status, but not with beta-cell antibodies or human leukocyte antigen-DQ type. PMID:11549675

De Block, C E; De Leeuw, I H; Decochez, K; Winnock, F; Van Autreve, J; Van Campenhout, C M; Martin, M; Gorus, F K

2001-09-01

323

Intracellular antibody immunity.  

PubMed

Antibodies allow the immune system to target pathogens despite their tremendous diversity and rapid evolution. Once bound to a pathogen, antibodies induce a broad range of effector mechanisms, including phagocytosis and complement. However, these mechanisms are all initiated in the extracellular space, meaning that pathogens like viruses evade them upon infection of their target cells. Recently, it has been shown that, in addition to mediating extracellular immune responses, antibodies also activate immunity inside infected cells. Antibodies that are bound to the surface of non-enveloped viruses or bacteria are carried into the cell during pathogen entry. Once inside the cell, these pathogen-attached antibodies are recognised by a highly conserved, high affinity cytosolic antibody receptor called TRIM21. TRIM21 initiates both sensor and effector responses that reduce viral replication and induce an antiviral state. These responses are an important part of antiviral immunity and the removal of TRIM21 results in uncontrolled viraemia and death in a mouse model of infection. PMID:24722852

Watkinson, Ruth E; McEwan, William A; James, Leo C

2014-07-01

324

STUDIES ON HUMAN ANTIBODIES  

PubMed Central

Human antibodies to blood group A substance were purified by absorption on columns of insoluble polyleucyl hog blood group A + H substance and eluted first with N-acetylgalactosamine and then with an A active reduced pentasaccharide ARL0.52. The ?M and ?G antibodies in these eluates were separated by density gradient centrifugation. The antibodies were studied for their relative capacities to be inhibited by various blood group A active oligosaccharides. Antibodies eluted by the N-acetylgalactosamine could be inhibited by N-acetylgalactosamine, as well as by lower concentrations of A active tri- and pentasaccharides, while those eluted by the pentasaccharide ARL0.52 could only be inhibited by the two oligosaccharides, but not by N-acetylgalactosamine, indicating that the N-acetylgalactosamine eluate had more antibodies with smaller size combining sites than the ARL0.52 eluate. Measurements by equilibrium dialysis gave values ranging from 2 x 103 to 1 x 105 M–1 and the values obtained with the ARL0.52 eluate were somewhat higher than those with the GalNAc eluate. Only one of three anti-A sera had ?M anti-A in the ARL0.52 eluate, while all three had ?M in the N-acetylgalactosamine eluate. Data on the precipitating, hemagglutinating, complement fixing, hemolytic properties of the eluted antibodies, and of their content of ? and ? light chains are given.

Moreno, Carlos; Kabat, Elvin A.

1969-01-01

325

Monoclonal antibodies and cancer therapy  

SciTech Connect

These proceedings collect papers on the subject of monoclonal antibodies. Topics include: Monoclonal antibody, biochemical effects and cancer therapeutic potential of tunicamycin, use of monoclonal antibodies for detection of lymph node metastases, active specific immunotherapy, and applications of monoclonal antibodies to investigations of growth factors.

Reisfeld, R.A.; Sell, S.

1985-01-01

326

Phage Display Derived Therapeutic Antibodies  

Microsoft Academic Search

This article gives an overview about the development of human therapeutic antibodies generated by phage dis- play. After an introduction to the method, the focus is on approved antibodies and those currently in clinical trials, 14 of which are described in detail. 1. ANTIBODY PHAGE DISPLAY In the mid 1980s, the development of recombinant tech- nologies for antibody chimerization and

Holger Thie; Torsten Meyer; Thomas Schirrmann; Michael Hust; Stefan Dubel

2008-01-01

327

Anti-EPHA2 antibody  

US Patent & Trademark Office Database

Problem to Be Solved It is intended to provide an antibody having an inhibitory activity against cell malignant transformation and/or tumor cell growth, etc. Solution The present invention provides an antibody which recognizes an epitope recognized by an antibody produced by a hybridoma SH348-1 (FERM BP-10836) or a hybridoma SH357-1 (FERM BP-10837), an antibody produced by the hybridoma SH348-1 or the hybridoma SH357-1, an antibody obtained by humanizing the antibody produced by the hybridoma SH348-1 or the hybridoma SH357-1, a pharmaceutical agent comprising the antibody as an active ingredient, etc.

2013-05-28

328

Serum auto antibodies presence in multiple sclerosis patients treated with beta-interferon 1a and 1b.  

PubMed

To verify the possible effect of IFN-beta treatment on auto antibodies development in multiple sclerosis (MS) we studied 69 MS patients before and during the treatment with IFN-beta 1b (n=35) and IFN-beta 1a (n=20) for 27 and 12 months respectively, and, as controls, 14 untreated MS patients. The serum, collected every 3 months from all the patients, was investigated for the presence of antinuclear (ANA), anti-smooth muscle (ASMA), anti-mitochondrial (AMA), anti-native DNA (nDNA) anti-cardiolipin (aCL), anti-parietal cells (APCA), anti-microsomal (AMC) and anti-tireoglobulin (ATG) antibodies. Among the IFN-beta 1b-treated MS patients an increase of the frequency and of the level of ANA, AMC and ATG was observed. ASMA and ANA antibodies were already present in about 45% of the MS patients before the treatment and fluctuated over the time. In one patient the treatment was interrupted after 6 months because of the occurrence of high ASMA level and of an autoimmune hepatitis. The data obtained in the smaller number of MS patients treated with IFN-beta 1a were very similar. No increase in aCL level was observed during both the IFN treatments. Our results indicate that the treatment with IFN-beta induces an increase of AMC and ATG antibodies in MS patients and confirm that, although rare, autoimmune diseases could be observed. The possible effect of these auto antibodies on the treatment efficacy and on MS clinical course need to be further investigated. PMID:10871787

Speciale, L; Saresella, M; Caputo, D; Ruzzante, S; Mancuso, R; Calvo, M G; Guerini, F R; Ferrante, P

2000-05-01

329

Positive Psychologists on Positive Constructs  

ERIC Educational Resources Information Center

Comments on the original article by McNulty and Fincham (see record 2011-15476-001). In their article, the authors offered compelling evidence that constructs such as forgiveness and optimism can have both beneficial and adverse consequences, depending on the context. Their caution about labeling particular psychological processes as "positive" is…

Lyubomirsky, Sonja

2012-01-01

330

Structural Comparison of Different Antibodies Interacting with Parvovirus Capsids? †  

PubMed Central

The structures of canine parvovirus (CPV) and feline parvovirus (FPV) complexed with antibody fragments from eight different neutralizing monoclonal antibodies were determined by cryo-electron microscopy (cryoEM) reconstruction to resolutions varying from 8.5 to 18 Å. The crystal structure of one of the Fab molecules and the sequence of the variable domain for each of the Fab molecules have been determined. The structures of Fab fragments not determined crystallographically were predicted by homology modeling according to the amino acid sequence. Fitting of the Fab and virus structures into the cryoEM densities identified the footprints of each antibody on the viral surface. As anticipated from earlier analyses, the Fab binding sites are directed to two epitopes, A and B. The A site is on an exposed part of the surface near an icosahedral threefold axis, whereas the B site is about equidistant from the surrounding five-, three-, and twofold axes. One antibody directed to the A site binds CPV but not FPV. Two of the antibodies directed to the B site neutralize the virus as Fab fragments. The differences in antibody properties have been linked to the amino acids within the antibody footprints, the position of the binding site relative to the icosahedral symmetry elements, and the orientation of the Fab structure relative to the surface of the virus. Most of the exposed surface area was antigenic, although each of the antibodies had a common area of overlap that coincided with the positions of the previously mapped escape mutations.

Hafenstein, Susan; Bowman, Valorie D.; Sun, Tao; Nelson, Christian D. S.; Palermo, Laura M.; Chipman, Paul R.; Battisti, Anthony J.; Parrish, Colin R.; Rossmann, Michael G.

2009-01-01

331

Defining antibody targets in Streptococcus oralis infection.  

PubMed Central

Immunoblotting of sera from 12 neutropenic patients with Streptococcus oralis septicemia and 18 patients with endocarditis due to viridans group streptococci revealed immunodominant S. oralis antigens at 85 and 180 kDa. The former cross-reacted with a mouse monoclonal antibody to hsp90. The latter was identified by sequencing positive clones obtained by screening a genomic expression library of S. oralis with pooled sera from patients who had been infected with S. oralis. Antibody eluted from one of these clones reacted with the 180-kDa antigen of S. oralis. Southern blotting confirmed the origin of the clone from S. oralis. The derived amino acid sequence showed 76.2% homology with the PAc protein precursor of Streptococcus mutans and 73.8% homology with the SpaA protein precursor of Streptococcus sobrinus. Epitope mapping of the derived amino acid sequence with sera from patients with viridans group streptococcal endocarditis delineated nine epitopes. Peptides 1 (TMYPNRQPGSGWDSS) and 2 (WYSLNGKIRAVDVPK), representing two of these epitopes, and peptide 3 (YEVEKPLEPAPVAPS), representing the repeat proline region, were synthesized. These three peptides were used to screen a phage antibody display library derived from a patient who had recovered from S. oralis infection. Two of the human recombinant antibodies produced (SORAL 3 and SORAL 4 against peptide 3) and a human recombinant antibody (B3.7) against the conserved epitope (LKVIRK) of hsp90 gave statistically significant protection, compared with control groups, in a mouse model of lethal S. oralis infection.

Burnie, J P; Brooks, W; Donohoe, M; Hodgetts, S; al-Ghamdi, A; Matthews, R C

1996-01-01

332

Antineurofilament and antiretinal antibodies in AIDS patients with cytomegalovirus retinitis.  

PubMed Central

Sera obtained from AIDS patients with cytomegalovirus (CMV) retinitis before and after treatment with foscarnet, AIDS patients with human immunodeficiency virus (HIV) retinopathy, AIDS patients without retinal disease, and normal healthy controls with and without positive CMV serologies were assayed for the presence of antibodies against the 200-kDa outer, 160-kDa middle, and 68-kDa core subunits of the neurofilament triplet. Additional studies were performed to determine the presence of antibodies reactive with proteins extracted from crude human retinal antigen preparations. Antibodies against the 200-, 260-, and 68-kDa proteins of the neurofilament triplet were detected in 15 of 15 AIDS patients with CMV retinitis. The expression of these antibodies was unaffected, qualitatively, by successful treatment with foscarnet. In contrast, only 30% of patients with HIV retinopathy unrelated to CMV, fewer than 35% of AIDS patients with positive CMV titers but without evident retinitis, and fewer than 25% of healthy controls with positive or negative CMV titers possessed antibodies against any of the triplet proteins (P < 0.001). Antibodies against several clusters of retinal antigens were also identified in the sera of patients with CMV retinitis. In summary, the data indicate that retinal elements damaged by CMV infection induce an antibody response against the 200-, 160-, and 68kDa components of the neurofilament triplet as well as other, as yet undefined retinal antigens. Images

Rosberger, D F; Tshering, S L; Polsky, B; Heinemann, M H; Klein, R F; Cunningham-Rundles, S

1994-01-01

333

Positioning apparatus  

DOEpatents

An apparatus is provided for precisely adjusting the position of an article relative to a beam emerging from a neutron source disposed in a housing. The apparatus includes a support pivotably mounted on a movable base plate and freely suspended therefrom. The support is gravity biased toward the housing and carries an article holder movable in a first direction longitudinally of the axis of said beam and normally urged into engagement against said housing. Means are provided for moving the base plate in two directions to effect movement of the suspended holder in two mutually perpendicular directions, respectively, normal to the axis of the beam.

Vogel, M.A.; Alter, P.

1983-07-07

334

Positioning apparatus  

DOEpatents

An apparatus for precisely positioning materials test specimens within the optimum neutron flux path emerging from a neutron source located in a housing. The test specimens are retained in a holder mounted on the free end of a support pivotably mounted and suspended from a movable base plate. The support is gravity biased to urge the holder in a direction longitudinally of the flux path against the housing. Means are provided for moving the base plate in two directions to effect movement of the holder in two mutually perpendicular directions normal to the axis of the flux path.

Vogel, Max A. (Kennewick, WA); Alter, Paul (Richland, WA)

1986-01-01

335

Positive Lives  

NSDL National Science Digital Library

The Positive Lives project is "a unique international project that photographs and documents the social and emotional impact of the global HIV/AIDS epidemic, illuminating positive human responses to this world crisis." Sponsored by the Levi Strauss Foundation and the Terrence Higgins Trust, the project has sponsored photographers from across the world to photograph various persons living with HIV/AIDS in a host of very different settings. While the project has sponsored a number of various photographic exhibits, this online collection represents a small portion of the work thus far. Using an interactive map of the world, users can click on different geographic areas to view photographic exhibits documenting the lived experience of this condition. In South Africa, visitors can learn about the work and the residents of Nazareth House, which is a children's home in Cape Town taking care of abandoned children with HIV or AIDS. In Edinburgh, visitors are taken through the lives of young drug abusers at the Muirhouse Estate who are also living with either HIV or AIDS. In the words of photographer John Sturrock, "In Muirhouse I witnessed the emotional struggle of people enduring a tragedy..." However, hope is present in these photographic essays as well, as they represent a broad range of emotions.

336

Evaluation of the sensitivity and specificity of six HIV combined p24 antigen and antibody assays  

Microsoft Academic Search

In this study, we evaluated the performance of six HIV combined p24 antigen and antibody (Ag\\/Ab) assays versus two third-generation anti-HIV antibody assays. The assays were evaluated using p24 antigen panel of 31 HIV-1 subtypes (n=124), 25 HIV-1 seroconversion panels (n=176), HIV-1 antibody positive samples including group M subtypes and group O (n=559), HIV-2 positive samples (n=110), and unselected HIV

Thoai Duong Ly; Syria Laperche; Catherine Brennan; Ana Vallari; Anne Ebel; Jeffrey Hunt; Lynn Martin; David Daghfal; Gerald Schochetman; Sushil Devare

2004-01-01

337

Development of syngeneic monoclonal anti-idiotype antibodies to mouse monoclonal anti-asialoglycoprotein receptor antibody.  

PubMed

Anti-idiotype antibodies (Ab2) play an important role in the homeostasis of immune responses and are related to the development and the disease activity of certain autoimmune diseases. The asialoglycoprotein receptor (ASGPR) is considered one of the target antigens in the pathogenesis of autoimmune chronic active hepatitis (AIH). We previously developed a mouse monoclonal antibody (clone 8D7) which recognizes rat and human ASGPR. In this study, to help investigate the anti-ASGPR antibody-anti-idiotype antibody network in patients with AIH, we developed a syngeneic mouse monoclonal Ab2 to the 8D7 anti-ASGPR antibody (Ab1). One clone, designated as 3C8, tested positive for specific reactivity to 8D7-Ab1 and did not bind to other irrelevant immunoglobulins. By competitive inhibition assays, the binding of 8D7-Ab1 to liver membrane extracts, i.e., the crude antigen preparation, was inhibited by 3C8-Ab2 in a dose-dependent manner, and the binding of 8D7-Ab1 to 3C8-Ab2 was inhibited by the liver membrane extracts. In the immunohistochemical analysis, 3C8-Ab2 blocked the specific staining of sinusoidal margins of rat hepatocytes by 8D7-Ab1. These results suggest that 3C8 anti-idiotype antibody recognizes the specific idiotypic determinants within the antigen-binding site of 8D7-Ab1. PMID:12108584

Hirai, Michio; Mizuno, Motowo; Morisue, Yoshiko; Yoshioka, Masao; Shimada, Morizou; Nasu, Junichirou; Okada, Hiroyuki; Shimomura, Hiroyuki; Yamamoto, Kazuhide; Tsuji, Takao

2002-06-01

338

Mapping of B-cell epitopes recognized by antibodies to histones in subsets of juvenile chronic arthritis.  

PubMed

The sera of 138 patients with juvenile chronic arthritis (JCA) were tested in ELISA with the five individual histones, 34 histone peptides covering the full length of the four core histones, and two peptides corresponding to the N- and C-terminal domains of H1. The occurrence of IgG antibodies was examined regarding the different subsets of JCA (pauciarticular, polyarticular, and systemic onset) and regarding clinical features (chronic anterior uveitis, CAU) and other serological features (antinuclear antibodies, ANA). Seventy-two percent of the 138 sera reacted with at least 1 histone peptide. The peptides 204-218 of H1, 1-25 of H2B, and 111-130 of H3 were recognized by 22-28% of JCA sera, and 42% of JCA sera reacted with one or both peptides 1-25 of H2B and 111-130 of H3. The frequency of occurrence of anti-histone antibodies (AHA) regarding the type of histone fraction (H1, H2A, H2B, H3 and H4) or the regions of histones was not significantly different in the three subsets of JCA. No obvious association was found between IgG antibodies to histone peptides and uveitis. In the subset of pauciarticular JCA, 13/31 patients (41.9%) with CAU against 14/41 patients (34.1%) without CAU possessed IgG antibodies reacting with peptides of the C-terminal domain 83-135 of H3. This difference is not statistically significant. Finally, the presence of antibodies to histones and histone peptides cannot completely explain ANA reactivity found in patients' sera. Although antibodies to histone peptides occur frequently in the serum of children with JCA, the antibody profiles seem to be highly individual and do not correlate with disease subtype or activity. Identification of AHA present not only in the circulation but also in tissue deposits may provide better insight into the identification of pathogenic antibodies. PMID:7541736

Stemmer, C; Tuaillon, N; Prieur, A M; Muller, S

1995-07-01

339

[Production of antibodies to aflatoxins].  

PubMed

A panel of ten monoclonal antibodies to aflatoxins B1, B2, and G2 was produced and comprehensively characterized. The affinity and cross reactivity of these antibodies were determined using the methods of direct, indirect, and competitive ELISA. The structures of monoclonal antibody genes were comprehensively studied and the variable and constant domains of the antibody genes were cloned and sequenced. Sequencing analysis confirmed the results of isotyping the light and heavy antibody chains obtained by ELISA. Variable and constant fragments of the antibody genes were cloned into a bicistron expression vector for the recombinant Fab' fragment for one of the antibodies expressed in Escherichia coli and purified. Thus, data were obtained that can be useful for the development of an aflatoxin detection system on the basis of the described monoclonal antibodies and the creation of recombinant antibodies with changed parameters of specificity using protein engineering methods. PMID:20386586

Kalinichenko, A A; Toporova, V A; Panina, A A; Aliev, T K; Kriukova, E A; Shemchukova, O B; Solopova, O N; Pozdniakova, L P; Sveshnikov, P G; Dolgikh, D A; Kirpichnikov, M P

2010-01-01

340

An Antibody Molecule  

NSDL National Science Digital Library

An antibody molecule. (A) Schematic drawing of a typical antibody molecule. As indicated, this protein is Y-shaped and has two identical binding sites for its antigen, one on either arm of the 3Y.2 The protein is composed of four polypeptide chains (two identical heavy chains and two identical and smaller light chains) held together by disulfide bonds. Each chain is made up of several different domains, here shaded either blue or gray. The antigen-binding site is formed where a heavy chain variable domain (VH) and a light chain variable domain (VL) come close together. These are the domains that differ most in their sequence and structure in different antibodies. (B) Ribbon drawing of a light chain showing the parts of the VL domain most closely involved in binding to the antigen in red; these contribute half of the fingerlike loops that fold around each of the antigen molecules in (A).

BEGIN:VCARD VERSION:2.1 FN:Martin Raff N:Raff;Martin REV:2005-04-15 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Julian Lewis N:Lewis;Julian REV:2005-04-15 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Alexander Johnson N:Johnson;Alexander REV:2005-04-15 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Dennis Bray N:Bray;Dennis REV:2005-04-15 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Bruce Alberts N:Alberts;Bruce REV:2005-04-15 END:VCARD; BEGIN:VCARD VERSION:2.1 FN:Keith Roberts N:Roberts;Keith REV:2005-04-15 END:VCARD

1998-07-01

341

Radiolabeled antibody fragments  

SciTech Connect

This patent describes an antibody conjugate of the formula: wherein Ab is the residue of a Fab fragment of a monoclonal antibody. The antibody being one which retains antigen-binding activity following enzymatic removal for the F/sub c/ fragment and reductive cleavage of the disulfide bond joining the heavy chains; -S- is the residue of the free sulfhydryl group of the Fab' fragment; R is a divalent organic linker; and R' is a nontoxic, weakly acidic chelating group capable of forming a chelate with a radionuclide metal ion that is thermodynamically stable under physiological conditions and has a higher stability constant than a chelate of the radionuclide with transferrin in vivo.

Nicolotti, R.A.

1989-06-06

342

Glycoproteomic Analysis of Antibodies*  

PubMed Central

Antibody glycosylation has been shown to change with various processes. This review presents mass spectrometric approaches for antibody glycosylation analysis at the level of released glycans, glycopeptides, and intact protein. With regard to IgG fragment crystallizable glycosylation, mass spectrometry has shown its potential for subclass-specific, high-throughput analysis. In contrast, because of the vast heterogeneity of peptide moieties, fragment antigen binding glycosylation analysis of polyclonal IgG relies entirely on glycan release. Next to IgG, IgA has gained some attention, and studies of its O- and N-glycosylation have revealed disease-associated glycosylation changes. Glycoproteomic analyses of IgM and IgE are lagging behind but should complete our picture of glycosylation's influence on antibody function.

Zauner, Gerhild; Selman, Maurice H. J.; Bondt, Albert; Rombouts, Yoann; Blank, Dennis; Deelder, Andre M.; Wuhrer, Manfred

2013-01-01

343

Immune Regulatory Antibodies  

PubMed Central

During the past decade, new insights into the mechanisms by which T-cell activation and proliferation are regulated have led to the identification of checkpoint proteins that either up- or down-modulate T-cell reactivity. In the presence of active malignancy, pathophysiologic inhibition of T-cell activity may predominate over stimulation. A number of antibodies have been generated that can block inhibitory checkpoint proteins or promote the activity of activating molecules. In murine models, their use alone or with a vaccine strategy has resulted in regression of poorly immunogenic tumors and cures of established tumors. The prototypical immune regulatory antibodies are those directed against cytotoxic T-lymphocyte antigen-4, a molecule present on activated T cells. In this review, the preclinical rationale and clinical experience with 2 anticytotoxic T-lymphocyte antigen-4 antibodies are extensively discussed, demonstrating that abrogation of an immune inhibitory molecule can result in significant regression of tumors and long-lasting responses. The unique kinetics of antitumor response and the characteristic immune-related side effects of ipilimumab are also discussed. This clinical efficacy of this promising antitumor agent has been evaluated in 2 randomized phase III trials, whose results are eagerly awaited. Programmed death (PD)-1 is another immune inhibitory molecule against which an abrogating human antibody has been prepared. Initial preclinical testing with anti–PD-1 and anti–PD-L1 has shown encouraging results. Stimulatory molecules such as CD40, 41-BB, and OX-40 are also targets for antibody binding and activation, not blockade, and early dose ranging trials with antibodies against all 3 have shown that they can mediate regression of tumors, albeit with their own spectrum of side effects that are different from those that occur with abrogation of immune inhibition.

Wolchok, Jedd D.; Yang, Arvin S.; Weber, Jeffrey S.

2014-01-01

344

The presence of non-organ-specific autoantibodies is associated with a negative response to combination therapy with interferon and ribavirin for chronic hepatitis C  

Microsoft Academic Search

BACKGROUND: Non-organ-specific autoantibodies are found in a considerable number of anti-HCV positive patients. Previous studies investigated the clinical relevance of these antibodies in patients treated with interferon monotherapy, but not combination therapies. METHODS: Anti-nuclear, anti-smooth muscle, anti-mitochondrial, anti-neutrophil-cytoplasmatic and anti-liver\\/kidney microsomal antibodies were determined in 78 consecutive anti-HCV positive patients by indirect immunofluorescence. The presence of these antibodies was related

Hermann E Wasmuth; Christian Stolte; Andreas Geier; Christoph G Dietrich; Carsten Gartung; Johann Lorenzen; Siegfried Matern; Frank Lammert

2004-01-01

345

Antineuronal antibodies and infectious pathogens in severe acute pediatric encephalitis.  

PubMed

The pathogenesis of acute encephalitis is divided into either direct infection or by immune-mediated inflammation, but the cause is still unknown. This retrospective study aimed to screen antineuronal antibodies in children with severe acute encephalitis. Thirty-four children (22 boys and 12 girls) underwent assessments such as antineuronal antibodies survey for autoimmune encephalitis and polymerase chain reaction/viral culture and antibody assays for all commonly recognized causes of infectious encephalitis. Sixteen (47.1%) were positive for autoantibodies, including antiglutamic acid decarboxylase antibodies in 16 and voltage-gated potassium channel complex antibodies in 1. Sixteen patients (47.1%) had presumed infectious etiologies, including 6 with influenza, 6 with Mycoplasma pneumoniae, 3 with enterovirus, and 1 with herpes simplex virus. In this study, influenza and Mycoplasma pneumoniae infection are the main presumed causes of severe acute encephalitis in children, although an immune-mediated mechanism may also play a role. PMID:23143714

Lin, Jainn-Jim; Lin, Kuang-Lin; Chiu, Cheng-Hsun; Hsia, Shao-Hsuan; Wang, Huei-Shyong; Chou, I-Jun; Lin, Yun-Tong

2014-01-01

346

Antibody-Antigen Interactions  

NSDL National Science Digital Library

The experimental protocol in this Web site is just one of many microbiology resources provided by the University of Leicester. The procedure guides students in finding the antibody concentration of a test antiserum and the number of antibody binding sites on an antigen molecule. A results graph and correct answers to the required calculations are given, providing the option of performing a virtual experiment in lieu of an actual one. This activity is probably most appropriate for high school and undergraduate level biology labs.

Cann, Alan.

2010-01-05

347

Therapeutic antibodies against cancer.  

PubMed

Antibody-based therapeutics against cancer are highly successful and currently enjoy unprecedented recognition of their potential; 13 monoclonal antibodies (mAbs) have been approved for clinical use in the European Union and in the United States. Bevacizumab, rituximab, and trastuzumab had sales in 2010 of more than $5 billion each. Hundreds of mAbs, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small-molecule drugs, and mAbs with optimized pharmacokinetics, are in clinical trials. However, deeper understanding of mechanisms is needed to overcome major problems including resistance to therapy, access to targets, complexity of biological systems, and individual variations. PMID:22520975

Adler, Mark J; Dimitrov, Dimiter S

2012-06-01

348

The activated seven lupus anticoagulant assay detects clinically significant antibodies.  

PubMed

Lupus anticoagulants are a heterogeneous group of autoantibodies detected by their effects on phospholipid-dependent coagulation assays. Persistent lupus anticoagulants are associated with thrombotic disease, but not all are clinically significant. Antibody heterogeneity and reagent and test variability dictate that at least 2 tests, of different types, should be used to screen lupus anticoagulants. The objective of this study was to investigate whether the activated seven lupus anticoagulant assay detects clinically significant antibodies. Eighty-two patients with antiphospholipid syndrome (APS) and 32 with systemic lupus erythematosus + positive for activated seven lupus anticoagulant and who were without thrombosis, who were positive by activated seven lupus anticoagulant assay, were investigated for lupus anticoagulants by dilute Russell's viper venom time, dilute activated partial thromboplastin time, and Taipan snake venom time, and for anticardiolipin antibodies. Fifty-seven of the APS patients were positive for lupus anticoagulants in multiple assays, 25 in activated seven lupus anticoagulant alone. Fourteen of the latter group were previously positive in other antiphospholipid antibodies assays, and 11 had only been positive for lupus anticoagulants by activated seven lupus anticoagulant. Twenty-eight had elevated anticardiolipin antibodies, 6 of whom were from the group that was positive in activated seven lupus anticoagulant only. Eight of the systemic lupus erythematosus + lupus anticoagulants (without thrombosis) patients were positive for lupus anticoagulant by activated seven lupus anticoagulant alone and had only been positive in activated seven lupus anticoagulant previously, and none had elevated anticardiolipin antibodies. The remaining 24 patients were lupus-anticoagulant positive in multiple assays, and 9 had elevated anticardiolipin antibodies. Dilute Russell's viper venom time and Dilute activated partial thromboplastin time are widely used to detect lupus anticoagulants and are considered to detect clinically significant antibodies. Activated seven lupus anticoagulant detected antibodies in APS patients who were positive by these assays and also lupus anticoagulants undetectable by the dilute Russell's viper venom time/dilute activated partial thromboplastin time reagents used, demonstrating its utility as a first-line or second-line assay. PMID:17895508

Moore, Gary W; Rangarajan, Savita; Savidge, Geoffrey F

2008-07-01

349

A mutagenesis study of a catalytic antibody.  

PubMed Central

We have generated seven site-specific mutations in the genes encoding the variable region of the heavy chain domain (VH) of the phosphocholine-binding antibody S107. S107 is a member of a family of well-characterized highly homologous antibodies that bind phosphorylcholine mono- and diesters. Two of these antibodies, MOPC-167 and T15, have previously been shown to catalyze the hydrolysis of 4-nitrophenyl N-trimethylammonioethyl carbonate. Two conserved heavy-chain residues, Tyr-33 and Arg-52, were postulated to be involved in binding and hydrolysis of 4-nitrophenylcholine carbonate esters. To more precisely define the catalytic roles of these residues, three Arg-52 mutants (R52K, R52Q, R52C) and four Tyr-33 mutants (Y33H, Y33F, Y33E, Y33D) of antibody S107 were generated. The genes encoding the VH binding domain of S107 were inserted into plasmid pUC-fl, and in vitro mutagenesis was performed. The wild-type and mutant S107 antibodies were expressed in P-3X63-Ag8.653 (P-3) myeloma cells by using a modified SV2 shuttle vector. The catalytic properties of wild-type antibody S107 are similar to those of the phosphocholine-specific antibody T15, which has the same VH protein sequence. In general, mutations at Tyr-33 had little effect on catalytic activity, whereas mutations at Arg-52 that result in loss of the positively charged side chain significantly lower the catalytic activity of S107. One mutant, Y33H, catalyzed the hydrolysis of 4-nitrophenyl N-trimethylammonioethyl carbonate with a kcat of 5.7 min-1 and a Km of 1.6 mM at pH 7.5. These results not only demonstrate the importance of electrostatic interactions in catalysis by antibody S107 but also show that catalytic side chains can be introduced into antibodies to enhance their catalytic efficiency.

Jackson, D Y; Prudent, J R; Baldwin, E P; Schultz, P G

1991-01-01

350

Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women.  

PubMed

Antithyroid antibodies (ATA) are found in 5-15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA are associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. This study evaluated the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)-embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI-embryo transfer cycles were prospectively enrolled in this study. Women positive for at least one of the thyroid antibodies, with normal thyroid-stimulating hormone (TSH) and free T4 concentrations and negative for anticardiolipin antibodies and lupus anticoagulant were included. ICSI was performed for fertilization in all cycles. Of 253 women, 219 were ATA negative and 34 ATA positive. Implantation rates (19.1% versus 18.4%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. The presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women was not found to significantly affect the outcome of ICSI-embryo transfer cycles. Antithyroid antibodies (ATA) can interact with thyroid hormone receptors located on the human oocyte and impair the chance of fertilization and healthy pregnancy. They are found in 5-15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA have been reported to be associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. The objective of our study was to evaluate the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)-embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI-embryo transfer cycles were prospectively enrolled in this study. Women with at least one of the thyroid antibodies positive and normal TSH and free T4 concentrations were included in the study. Since other immunological disorders might affect the results, antiphospholipid antibodies (APA), which are the markers of antiphospholipid antibody syndrome, were also screened in all women prior to study. Women with positive for APA were excluded in the final analysis. Of 253 women, 219 (86.6%) were ATA negative and 34 (13.4%) ATA positive. Implantation rates (19.1% versus 18.4%), biochemical pregnancy rates (9.2% versus 14.3%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. In conclusion, presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women does not affect the outcome of ICSI-embryo transfer cycles. PMID:23953066

Karacan, Meric; Alwaeely, Faiz; Cebi, Ziya; Berberoglugil, Munip; Batukan, Melike; Ulug, Murat; Arvas, Ayse; Caml?bel, Teksen

2013-10-01

351

Selection of recombinant antibodies from antibody gene libraries.  

PubMed

Antibodies are indispensable detection reagents for research and diagnostics and represent the biggest class of biological therapeutics on the market. In vitro antibody selection systems offer many advantages over animal-based technologies because the whole selection process is independent of the in vivo immune response. In the last two decades antibody phage display has evolved to the most robust and widely used method and has already yielded thousands of antibodies. The selection of binders by phage display is also referred to as "panning" and based on the specific molecular interaction of antibody phage with an immobilized antigen thus allowing the enrichment and isolation of antigen-specific monoclonal binders from very large antibody gene libraries. Here, we give detailed protocols for the selection of recombinant antibody fragments from antibody gene libraries in microtiter plates. PMID:24233787

Hust, Michael; Frenzel, André; Schirrmann, Thomas; Dübel, Stefan

2014-01-01

352

HLA Antibodies and Neonatal Alloimmune Thrombocytopenia  

Microsoft Academic Search

A female baby with a severe thrombocytopenia at 18 × 109\\/l was born to a 29-year-old (gestation 2\\/partum 2) mother. Scattered petechiae were present on her legs, arms, chest and face, but there was no bleeding, infection, fever or hepatosplenomegaly. A platelet antibody screening immunocapture test was positive, which was performed on the mother’s serum 3, 12 and 38 days

P. Moncharmont; V. Dubois; C. Obegi; M. Vignal; Y. Mérieux; L. Gebuhrer; D. Rigal

2004-01-01

353

Antibodies to human caudate nucleus neurons in Huntington's chorea.  

PubMed Central

Antibodies reacting with neuronal cytoplasmic antigens present in normal human caudate and subthalamic nuclei were detected in 37 of 80 probands afflicted with Huntington's disease (HD). IgG antibodies were detected by immunofluorescence using frozen sections of unfixed normal human and rat brain. Specificity of IgG binding was confirmed using pepsin F(ab')2 fragments of IgG isolated from positive sera. In vitro complement fixation of IgG antibody was detected in 22 of 31 sera tested. Neuronal cytoplasmic antigens reacting with positive HD sera were diminished after trypsin or RNAase treatment of tissue sections but were not removed by DNAase, neuraminidase, EDTA, or dithiothreitol treatment. Antibody staining of neurons could be removed after absorption with isolated caudate nucleus neurons or by using perchloroacetic acid extracts of caudate nucleus. Prevalence of antibody reacting with neuronal cytoplasm was 3% in 60 normal controls and 6% among a wide variety of patients with diverse neurological disorders. However, one-third of 33 patients with Parkinson's disease showed presence of antineuronal antibody. Among patients with HD, a significant association was noted between duration of clinical disease greater than 7 yr and titers of antibody of 1:2 or greater (P less than 0.001). When 115 family members of HD probands were tested, 30% of unaffected spouses showed presence of antineuronal antibody. 23.2% of first-degree relatives at risk for developing HD was also positive (P less than 0.001). 10.5% of second-degree relatives showed presence of antineuronal antibody. These data may support an environmental or infectious factor somehow involved in the ultimate expression of HD. Images

Husby, G; Li, L; Davis, L E; Wedege, E; Kokmen, E; Williams, R C

1977-01-01

354

Monoclonal antibody based ELISA tests to detect antibodies against neuraminidase subtypes 1, 2 and 3 of avian influenza viruses in avian sera  

Microsoft Academic Search

The objective of this study was the development and the evaluation of competitive ELISA assays based on monoclonal antibodies for the detection of antibodies specific for neuraminidase type 1 (N1), 2 (N2) and 3 (N3) in avian sera. A total of 1450 sera from different avian species (854 negative, 185 positive to N1, 136 positive to N2, 219 positive to

Ana Moreno; Emiliana Brocchi; Davide Lelli; Daniela Gamba; Massimo Tranquillo; Paolo Cordioli

2009-01-01

355

Sandwich antibody arrays using recombinant antibody-binding protein L.  

PubMed

Antibody arrays are a useful for detecting antigens and other antibodies. This technique typically requires a uniform and well-defined orientation of antibodies attached to a surface for optimal performance. A uniform orientation can be achieved by modification of antibodies to include a single site for attachment. Thus, uniformly oriented antibody arrays require a bioengineered modification for the antibodies directly immobilization on the solid surface. In this study, we describe a "sandwich-type" antibody array where unmodified antibodies are oriented through binding with regioselectively immobilized recombinant antibody-binding protein L. Recombinant proL-CVIA bearing C-terminal CVIA motif is post-translationally modified with an alkyne group by protein farnesyltransferase (PFTase) at the cysteine residue in the CVIA sequence to give proL-CVIApf, which is covalently attached to an azido-modified glass slide by a Huisgen [3 + 2] cycloaddition reaction. Slides bearing antibodies bound to slides coated with regioselectively immobilized proL-CVIApf gave stronger fluorescence outputs and those where the antibody-binding protein was immobilized in random orientations on an epoxy-modified slide. Properly selected capture and detection antibodies did not cross-react with immobilized proL-CVIApf in sandwich arrays, and the proL-CVIApf slides can be used for multiple cycles of detected over a period of several months. PMID:24841983

Seo, Jin-Soo; Poulter, C Dale

2014-06-10

356

Double Antibody ELISA for HEV Antigen and Antibody.  

National Technical Information Service (NTIS)

The objects of the invention are: to provide a more sensitive and specific assay for HEV antibody and antigen than the previously described single-antibody ELISA; to provide a facile and effective means for determining titers of maternal antibody to HEV i...

K. Nazerian L. F. Lee

1990-01-01

357

Monoclonal antibodies in haematopathology  

SciTech Connect

This book contains over 40 selections. Some of the titles are: Oncogene (c-myc, c-myb) amplification in acute myelogenous leukaemia; Ultrastructural characterization of leukaemic cells with monoloclonal antibodies; Origin of B-cell malignancies; Immunohistology of gut lymphomas; and Spurious evidence of lineage infidelity in monocytic leukaemia.

Grignani, F.; Martelli, M.F.; Mason, D.Y.

1985-01-01

358

Reshaping Antibody Diversity  

PubMed Central

Summary Unlike humans or mice, some species have limited genome encoded combinatorial diversity potential, yet mount a robust antibody response. Cows are unusual in having exceptionally long CDR H3 loops and few V-regions, but the mechanism for creating diversity is not understood. Deep sequencing revealed that ultralong CDR H3s contain a remarkable complexity of cysteines, suggesting that disulfide-bonded mini-domains may arise during repertoire development. Indeed, crystal structures of two cow antibodies reveal that these CDR H3s form a very unusual architecture composed of a ?-strand “stalk” that supports a structurally diverse, disulfide-bonded, “knob” domain. Sequence analysis suggests that diversity arises from somatic hypermutation of an ultralong DH with a severe codon bias towards mutation to cysteine. These unusual antibodies can be elicited to recognize defined antigens through the knob domain. Thus, the bovine immune system produces an antibody repertoire composed of CDR H3s of unprecedented length that fold into a diversity of mini-domains generated through combinations of somatically generated disulfides.

Wang, Feng; Ekiert, Damian C.; Ahmad, Insha; Yu, Wenli; Zhang, Yong; Bazirgan, Omar; Torkamani, Ali; Raudsepp, Terje; Mwangi, Waithaka; Criscitiello, Michael F.; Wilson, Ian A.; Schultz, Peter G.; Smider, Vaughn V.

2014-01-01

359

Therapeutic antibody engineering  

PubMed Central

It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.

Parren, Paul W.H.I.; Lugovskoy, Alexey A.

2013-01-01

360

Antibodies for CFTR studies  

Microsoft Academic Search

Abstract For most expression studies focusing on the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, sensitive and specific antibodies (Abs) are critically needed. Several Abs have been produced commercially,or by research laboratories for CFTR detection in both cell lines with heterologous or endogenous expression and native cells\\/tissues. Here, we review the applicability of most Abs currently in use in CF

Filipa Mendes; Carlos M. Farinha; M Onica Roxo-rosa; Pascale Fanen; Aleksander Edelman; Robert Dormer; Margaret Mcpherson; Heather Davidson; Edith Puchelle; Hugo De Jonge; Ghanshyam D. Heda; Martina Gentzsch; Gergely L. Lukacs; Deborah Penque; Margarida D. Amaral

361

Antibodies for CFTR studies  

Microsoft Academic Search

For most expression studies focusing on the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, sensitive and specific antibodies (Abs) are critically needed. Several Abs have been produced commercially or by research laboratories for CFTR detection in both cell lines with heterologous or endogenous expression and native cells\\/tissues. Here, we review the applicability of most Abs currently in use in CF

Filipa Mendesa; Carlos M. Farinhaa; Pascale Fanenc; Robert Dormere; Ghanshyam D. Hedai; Gergely L. Lukacsk; Margarida D. Amarala; Ricardo Jorge; S. C. Johnson

362

Antibodies for CFTR studies  

Microsoft Academic Search

For most expression studies focusing on the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein, sensitive and specific antibodies (Abs) are critically needed. Several Abs have been produced commercially or by research laboratories for CFTR detection in both cell lines with heterologous or endogenous expression and native cells\\/tissues. Here, we review the applicability of most Abs currently in use in CF

Filipa Mendes; Carlos M. Farinha; Mónica Roxo-Rosa; Pascale Fanen; Aleksander Edelman; Robert Dormer; Margaret McPherson; Heather Davidson; Edith Puchelle; Hugo De Jonge; Ghanshyam D. Heda; Martina Gentzsch; Gergely Lukacs; Deborah Penque; Margarida D. Amaral

2004-01-01

363

Humanized Antibodies for Antiviral Therapy  

NASA Astrophysics Data System (ADS)

Antibody therapy holds great promise for the treatment of cancer, autoimmune disorders, and viral infections. Murine monoclonal antibodies are relatively easy to produce but are severely restricted for therapeutic use by their immunogenicity in humans. Production of human monoclonal antibodies has been problematic. Humanized antibodies can be generated by introducing the six hypervariable regions from the heavy and light chains of a murine antibody into a human framework sequence and combining it with human constant regions. We humanized, with the aid of computer modeling, two murine monoclonal antibodies against herpes simplex virus gB and gD glycoproteins. The binding, virus neutralization, and cell protection results all indicate that both humanized antibodies have retained the binding activities and the biological properties of the murine monoclonal antibodies.

Co, Man Sung; Deschamps, Marguerite; Whitley, Richard J.; Queen, Cary

1991-04-01

364

The Art of Making Antibodies.  

ERIC Educational Resources Information Center

Provides background information for teachers on the nature and production of antibodies. Points out that the production of monoclonal antibodies blends the malignant with the beneficial to create a medical tool of exciting potential. (JN)

Headon, Denis R.

1986-01-01

365

Langmuir films from antibodies based on amphiphilic polyelectrolytes.  

PubMed

A technique for forming Langmuir films from antibodies based on an amphiphilic polyelectrolyte was developed. The physicochemical and immunochemical properties of the Langmuir films obtained were studied. The interaction of HBsAg with the films was found to be described by a model with one binding site, whereas that of HBsAg with antibodies adsorbed on a polystyrene plate, by a model with a positive cooperativity. The use of the novel Langmuir films from antibodies increases the sensitivity of the immunoenzyme assay. PMID:9231367

Babitskaya, J I; Budashov, I A; Chernov, S F; Kurochkin, I N; Doroshenko, N V; Zubov, S V

1997-01-01

366

[Antierythrocyte antibodies due to ovarian dysgerminoma. A case report].  

PubMed

The case of a 24-year-old woman with fever, abdominal pain and weight loss, is presented. Right ovarian dysgerminoma was diagnosed; group A blood, negative direct Coombs. The search for free serum antibodies was positive, with specificity: auto anti 1, anti P with activity at 37 degrees C. Hysterectomy, appendectomy, omentectomy and retroperitoneal ganglia biopsy, were performed; the latter one showed metastasis. Blood transfusions were given. Thirty days postoperative, the red cell polyagglutination had disappeared, as well as antibodies. PMID:2076838

Mejía López, D; Baptista González, H A; Rosenfeld Mann, F; Tenorio González, F; Domínguez Chilabert, V; Santarosa Pérez, M A; Quintanar García, E

1990-12-01

367

Porcine reproductive and respiratory syndrome antibody detection on filter discs  

Microsoft Academic Search

Summary Two enzyme-linked immunosorbent assay (ELISA) kits were evaluated for detection of porcine reproductive and respiratory syndrome (PRRS) antibodies in pooled sera and filter discs (FDs). Elution and incubation procedures and positive thresholds for both ELISAs were determined using FDs collected from sixty non- infected pigs and five pigs with low PRRS-antibody titres. Eighty paired samples (serum\\/FD) from infected pigs

E. Albina

2003-01-01

368

[Immobilization of von Willebrand factor antibody on solid host membranes].  

PubMed

This study aimed at immobilizing the antibodies on the surfaces of the solid host membranes in order to improve the property of the biomaterial. The von Willebrand factor (vWf) antibodies were immobilized on the surface of Bombyx mori silk fibroin and PLA (Poly Lactic Acid) membrane by NH3 plasma treatment followed by covalent cross-linking reaction. The immobilization efficiency was evaluated by two methods including the antibody surplus and enzyme-linked immunosorbent assay (ELISA). The in vitro antithrombogenicity representing the activity of immobilized vWf antibody was determined by the method of Activated Partial Thromboplastin Time (APTT), Prothrombin Time (PT) and Thrombin Time (TT) test. The results demonstrate that the vWf antibodies are immobilized on silk fibroin and PLA membranes in an efficient way with the efficiency of antibody surplus up to 23.88% and ELISA reaction is positive. APTT and TT exceeded the upper limits distinctly, but the value of PT did not change noticeably. The in vitro antithrombogenicity represented the is activity-retaining form of antibodies. These results extend the application of antibody immobilization technique and provide a new idea about the design of biomaterials relating to the coagulation factors. PMID:16294733

Gao, Yunhua; Yang, Xinlin

2005-10-01

369

Calculation of Monoclonal Antibody Affinity Constants Directly from Antibody Dilution Curves.  

National Technical Information Service (NTIS)

A method for estimating the affinity constants of monoclonal antibody directly from antibody dilution curves is described. Antibody affinity is a major determinant of the interaction of antigen with antibody. Knowledge of antibody affinity, as well as spe...

W. R. Griswold D. P. Nelson

1985-01-01

370

Capacity for Infectious HIV-1 Virion Capture Differs by Envelope Antibody Specificity  

PubMed Central

Antibody capacity to recognize infectious virus is a prerequisite of many antiviral functions. We determined the infectious virion capture index (IVCI) of different antibody specificities. Whereas broadly neutralizing antibodies (bNAbs), except for an MPER bNAb, selectively captured infectious virions, non-bNAbs and mucosal human immunodeficiency virus type 1 (HIV-1)-positive IgG captured subsets of both infectious and noninfectious virions. Infectious virion capture was additive with a mixture of antibodies, providing proof of concept for vaccine-induced antibodies that together have improved capacity to recognize infectious virions.

Liu, Pinghuang; Williams, LaTonya D.; Shen, Xiaoying; Bonsignori, Mattia; Vandergrift, Nathan A.; Overman, R. Glenn; Moody, M. Anthony; Liao, Hua-Xin; Stieh, Daniel J.; McCotter, Kerrie L.; French, Audrey L.; Hope, Thomas J.; Shattock, Robin; Haynes, Barton F.

2014-01-01

371

Comparison of two immunofluorescence tests for detecting antibodies to C. trachomatis.  

PubMed

Two immunofluorescence tests were compared for detecting antibodies to chlamydiae. The inclusion antigen test was more sensitive, detecting antibodies in more sera and at higher titres. The micro-IF test was more specific, differentiating between antibodies to C. trachomatis and those to C.IOL 207. Antibodies to this non-genital chlamydial type accounted for half the positive results. These antibodies can cause the prevalence of C. trachomatis infections to be over estimated when genus-specific serology tests are used. PMID:3533611

Forsey, T; Stainsby, K; Hoger, P H; Ridgway, G L; Darougar, S; Fischer-Brugge, U

1986-06-01

372

Interferon-beta antibodies have a higher affinity in patients with neutralizing antibodies compared to patients with non-neutralizing antibodies.  

PubMed

In this study, we investigated the affinity, determined by a relative affinity assay, using increasing concentrations of sodium-isothiocyanate to disrupt the antigen antibody binding of neutralizing and non-neutralizing antibodies against interferon-beta (IFNbeta)-1a and -1b in 73 serum samples of MS patients treated with IFNbeta-1a or -1b. Relative affinity values were significantly higher in NAB-positive compared to NAB-negative samples and in samples of IFNbeta-1a-treated patients compared to IFNbeta-1b. A significant positive correlation between relative affinity values and therapy duration indicates affinity maturation as another qualitative factor in IFNbeta neutralization. PMID:16556466

Gneiss, C; Tripp, P; Ehling, R; Khalil, M; Lutterotti, A; Egg, R; Mayringer, I; Künz, B; Berger, T; Reindl, M; Deisenhammer, F

2006-05-01

373

Aspergillus fumigatus-specific antibodies in allergic bronchopulmonary aspergillosis and aspergilloma: evidence for a polyclonal antibody response.  

PubMed Central

Patients with the Aspergillus-induced diseases allergic bronchopulmonary aspergillosis (ABPA), aspergilloma (fungus ball), and Aspergillus skin test-positive asthma were differentiated immunologically by radioimmunoassay based on their total immunoglobulin E (IgE) and Aspergillus fumigatus-specific IgE levels. In this study, a new, highly sensitive biotin-avidin-linked immunosorbent assay was used to evaluate A. fumigatus-specific antibodies of all immunoglobulin classes. Studied populations included 13 patients with ABPA, 12 with aspergilloma, 9 with Aspergillus skin test-positive asthma, and 9 normal individuals without asthma. A. fumigatus-specific antibodies of all classes were elevated in patients with ABPA, variably elevated in those with aspergilloma, and lowest in the other two groups. This assay demonstrated significantly higher specific IgE antibody levels in the ABPA group over those of the other groups, even with 1:1,000 dilutions of the sera. This study demonstrated that ABPA is a disease characterized by a polyclonal antibody response to Aspergillus antigen and not just a response to IgE and IgG antibody classes. The measurement of other antibody classes, particularly IgD and IgA, could enhance the immunodiagnosis of ABPA. The biotin-avidin-linked immunosorbent assay was found to be a highly sensitive assay that can be a clinically useful alternative to radioimmunoassay in the measurement of A. fumigatus-specific antibodies.

Brummund, W; Resnick, A; Fink, J N; Kurup, V P

1987-01-01

374

Monoclonal Antibody Pharmacokinetics and Pharmacodynamics  

Microsoft Academic Search

More than 20 monoclonal antibodies have been approved as therapeutic drugs by the US Food and Drug Administration, and it is quite likely that the number of approved antibodies will double in the next 7–10 years. Antibody drugs show several desirable characteristics, including good solubility and stability, long persistence in the body, high selectivity and specificity, and low risk for

W Wang; EQ Wang; JP Balthasar

2008-01-01

375

Antibody-gold cluster conjugates  

DOEpatents

Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be about 5.0 nm. Methods and reagents are disclosed in which antibodies or Fab' fragments thereof are covalently bound to a stable cluster of gold atoms. 2 figs.

Hainfeld, J.F.

1988-06-28

376

Detection of IgG antibody to Epstein-Barr virus viral capsid antigen in saliva by antibody capture radioimmunoassay  

Microsoft Academic Search

A ‘G’ antibody capture radioimmunoassay (GACRIA) to detect IgG to Epstein-Barr virus (EBV) viral capsid antigen (VCA) in saliva is described. The monoclonal antibody to EBV VCA used in the GACRIA bound non-specifically when testing saliva samples having a total IgG content of less than 2.0 mg\\/l, so giving false positive results. This problem was overcome by including 0.5% EBV-negative

A. J. Vyse; W. A. Knowles; B. J. Cohen; D. W. G. Brown

1997-01-01

377

From whole monoclonal antibodies to single domain antibodies: think small.  

PubMed

The development of therapeutic monoclonal antibodies over the last 35 years has led to the emergence of a new class of useful therapeutic molecules. These "first generation" antibodies have been obtained thanks to the conjugated and huge efforts of both academic and biotech researchers. About 30 monoclonal antibodies are currently approved for therapeutic use in Europe, USA, and China. Strikingly, only a restricted number of these antibodies are immunoglobulin fragments, single variable domains, or multiunit formats based on the engineering of immunoglobulin variable domains. In the present chapter, we will review the major steps of the therapeutic antibodies history and we will highlight the enormous potential of antibody fragments, either used as multiunits such as bispecific antibodies, single units, or as cell modifiers such as intrabodies or cell surface-expressed molecules. PMID:22886242

Teillaud, Jean-Luc

2012-01-01

378

Antichlamydial antibodies in pelvic inflammatory disease.  

PubMed

The role of Chlamydia trachomatis in pelvic inflammatory disease (PID) diagnosed without laparoscopy was assessed by measuring antichlamydial antibodies in the patient's serum and by comparing the results with those in patients with uncomplicated non-specific genital infection (NSGI) and gonorrhoea and in non-infected controls. A modified microimmunofluorescence test was used. Patients with severe PID had significantly more positive antichlamydial IgG and IgM results than did control subjects, patients with gonorrhoea, and patients with NSGI. Less severe PID was associated with significantly raised levels of antichlamydial IgG antibodies compared with NSGI and controls and with raised levels of IgM antibodies compared with controls. Two patients with PID had lower genital tract gonorrhoea, one of whom had raised antichlamydial antibody levels. These findings may indicate a mixed infection and therapy should be reviewed in such patients. A serological diagnosis of chlamydial infection is relatively easy and cheap and enables a rapid diagnosis of chlamydial infection to be made. PMID:526845

Simmons, P D; Forsey, T; Thin, R N; Treharne, J D; Darougar, S; Langlet, F; Pandhi, R K

1979-12-01

379

New antibody conjugates in cancer therapy.  

PubMed

Targeting of radiation, drugs, and protein toxins to cancers selectively with monoclonal antibodies (MAbs) has been a topic of considerable interest and an area of continued development. Radioimmunotherapy (RAIT) of lymphoma using directly labeled MAbs is of current interest after approval of two radiolabeled anti-CD20 MAbs, as illustrated with the near 100% overall response rate obtained in a recent clinical trial using an investigational radiolabeled anti-CD22 MAb, 90Y-epratuzumab. The advantage of pretargeted RAIT over directly labeled MAbs is continuing to be validated in preclinical models of lymphoma and solid tumors. Importantly, the advantages of combining RAIT with radiation sensitizers, with immunotherapy, or a drug conjugate targeting a different antigen are being studied clinically and preclinically. The area of drug-conjugated antibodies is progressing with encouraging data published for the trastuzumab-DM1 conjugate in a phase I clinical trial in HER2-positive breast cancer. The Dock-and-Lock platform technology has contributed to the design and the evaluation of complex antibody-cytokine and antibody-toxin conjugates. This review describes the advances made in these areas, with illustrations taken from advances made in the authors' institutions. PMID:20953556

Govindan, Serengulam V; Goldenberg, David M

2010-01-01

380

Subcutaneous Administration of Monoclonal Antibodies in Oncology  

PubMed Central

Treatment with monoclonal antibodies (mabs) has become an established component of oncological therapy. The monoclonal antibodies available for this purpose are mainly administered intravenously in individually adapted doses according to body weight over longer treatment times. For other chronic diseases such as, for example, diabetes mellitus, the subcutaneous administration of drugs is an established therapy option. For the subcutaneous administration of larger volumes as needed for mab solutions the extracellular matrix of the subcutaneous tissue represents a problem. The co-formulation with recombinant human hyaluronidase makes the relatively pain-free administration of larger fluid volumes and thus the subcutaneous administration of monoclonal antibodies possible, as illustrated by the development of a subcutaneous formulation of trastuzumab. This constitutes a less invasive, time-optimised and flexible form of administration for patients with HER2-positive breast cancer that, with its fixed dosing possibilities, contributes to therapeutic safety. The example of trastuzumab shows that the subcutaneous administration of monoclonal antibodies can simplify oncological long-term therapy not only for the patients but also for the medical personnel.

Jackisch, C.; Muller, V.; Maintz, C.; Hell, S.; Ataseven, B.

2014-01-01

381

Fluoroimmunoassays using antibody-conjugated quantum dots.  

PubMed

Luminescent colloidal semiconductor nanocrystals (quantum dots) are robust inorganic fluoro phores that have the potential to circumvent some of the functional limitations encountered by organic dyes in sensing and biotechnological applications. Quantum dots exhibit size-dependent tunable, narrow fluorescence emission spectra that span the visible spectrum and have broad absorption spectra. This allows simultaneous excitation of several particle sizes at a single wavelength with emission at multiple wavelengths. Quantum dots also provide a high-resistance threshold to chemical degradation and photodegradation. We have developed a conjugation strategy for the attachment of antibodies to quantum dots based on electrostatic interactions between negatively charged dihydrolipoic acid (DHLA)-capped CdSe-ZnS core-shell quantum dots and positively charged proteins (natural or engineered) that serve to bridge the quantum dot and antibody. This chapter details the materials and methods for synthesis of the DHLA-capped CdSe-ZnS core-shell quantum dots, the construction and preparation of recombinant proteins, the conjugation of antibodies to quantum dots, and the use of antibody-coated quantum dots in a fluoroimmunoassay. PMID:15923672

Goldman, Ellen R; Mattoussi, Hedi; Anderson, George P; Medintz, Igor L; Mauro, J Matthew

2005-01-01

382

Antibody Engineering and Therapeutics Conference  

PubMed Central

The Antibody Engineering and Therapeutics conference, which serves as the annual meeting of The Antibody Society, will be held in Huntington Beach, CA from Sunday December 8 through Thursday December 12, 2013. The scientific program will cover the full spectrum of challenges in antibody research and development, and provide updates on recent progress in areas from basic science through approval of antibody therapeutics. Keynote presentations will be given by Leroy Hood (Institute of System Biology), who will discuss a systems approach for studying disease that is enabled by emerging technology; Douglas Lauffenburger (Massachusetts Institute of Technology), who will discuss systems analysis of cell communication network dynamics for therapeutic biologics design; David Baker (University of Washington), who will describe computer-based design of smart protein therapeutics; and William Schief (The Scripps Research Institute), who will discuss epitope-focused immunogen design.   In this preview of the conference, the workshop and session chairs share their thoughts on what conference participants may learn in sessions on: (1) three-dimensional structure antibody modeling; (2) identifying clonal lineages from next-generation data sets of expressed VH gene sequences; (3) antibodies in cardiometabolic medicine; (4) the effects of antibody gene variation and usage on the antibody response; (5) directed evolution; (6) antibody pharmacokinetics, distribution and off-target toxicity; (7) use of knowledge-based design to guide development of complementarity-determining regions and epitopes to engineer or elicit the desired antibody; (8) optimizing antibody formats for immunotherapy; (9) antibodies in a complex environment; (10) polyclonal, oligoclonal and bispecific antibodies; (11) antibodies to watch in 2014; and (12) polyreactive antibodies and polyspecificity.

Almagro, Juan Carlos; Gilliland, Gary L; Scott, Jamie; Larrick, James W; Pluckthun, Andreas; Veldman, Trudi; Adams, Gregory P; Parren, Paul WHI; Chester, Kerry A; Bradbury, Andrew; Reichert, Janice M; Huston, James S

2013-01-01

383

Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas  

PubMed Central

We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-?) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-? and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-? test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-? test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-? positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-? test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations.

Holder, Tom; Clifford, Derek; Dexter, Ian; Brewer, Jacky; Smith, Noel; Waring, Laura; Crawshaw, Tim; Gillgan, Steve; Lyashchenko, Konstantin; Lawrence, John; Clarke, John; de la Rua-Domenech, Ricardo; Vordermeier, Martin

2012-01-01

384

Evaluation of gamma interferon and antibody tuberculosis tests in alpacas.  

PubMed

We describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-?) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas from Mycobacterium bovis culture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-? and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-? test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-? test was at least in part due to undisclosed Mycobacterium microti infection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-? positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-? test with two antibody tests in a "test package," although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations. PMID:22914362

Rhodes, Shelley; Holder, Tom; Clifford, Derek; Dexter, Ian; Brewer, Jacky; Smith, Noel; Waring, Laura; Crawshaw, Tim; Gillgan, Steve; Lyashchenko, Konstantin; Lawrence, John; Clarke, John; de la Rua-Domenech, Ricardo; Vordermeier, Martin

2012-10-01

385

Site-specific antibody-drug conjugation through glycoengineering.  

PubMed

Antibody-drug conjugates (ADCs) have been proven clinically to be