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Autoimmune thyroiditis in antinuclear antibody positive children without rheumatologic disease  

Microsoft Academic Search

BACKGROUND: Children are commonly referred to a pediatric rheumatology center for the laboratory finding of an Anti-nuclear antibody (ANA) of undetermined significance. Previous studies regarding adult rheumatology patients have supported an association between ANA and anti-thyroid antibodies, with the prevalence of thyroid antibodies being significantly higher in patients referred to a rheumatology center for an ANA without evidence of connective

Kathryn S Torok; Thaschawee Arkachaisri



ANA (Antinuclear Antibody Test)  


... Web Lupus Foundation of America American College of Rheumatology: Antinuclear Antibodies (ANA) American Autoimmune Related Diseases Association: ... 2009 April). Antinuclear Antibodies (ANA). American College of Rheumatology [On-line information]. Available online at http://www. ...


Relation between Isolated Venous Thrombi in Soleal Muscle and Positive Anti-Nuclear Antibody  

PubMed Central

Objective: In patients with isolated soleal vein thrombosis (SVT), the relation between acute thrombi and positive anti-nuclear antibody (ANA) was investigated. Subjects and Methods: The subjects were 116 lower extremities in 86 patients with SVT. They were diagnosed and examined by ultrasonography and blood serum analysis (D-dimer, ANA), and had been followed up every three months. Results: They had acute SVT in 35 limbs (30%) and chronic SVT in 86 limbs (70%), and they had positive ANA in 63%. They had recurrent SVT in 26%, and all were positive for ANA. Conclusion: ANA-positivity might be a risk factor for acute thrombi in patients with SVT. (*English Translation of J Jpn Coll Angiol 2010; 50: 417-422.)



A positive anti-nuclear antibody result does not contraindicate living kidney donation.  


Autoantibodies may precede the clinical onset of disease in up to two-thirds of patients with systemic lupus erythematosus (SLE). There is thus concern that antinuclear antibody (ANA) positivity in living kidney donors may eventuate in development of lupus nephritis post-uninephrectomy. Post-uninephrectomy, we routinely examine living kidney donors at 6 weeks, 6 months, 12 months, and annually thereafter. We performed a retrospective review of living kidney donors who had undergone uninephrectomy between July 1, 1999, and December 1, 2008. Data were collected for pre- and post-uninephrectomy renal function, proteinuria, hematuria, ANA, and anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies. Among 68 living donor uninephrectomies performed during the study period, we excluded patients with no pre- uninephrectomy ANA or defaulted postoperative follow-up (n = 2). Twelve (18.2%) living donors were ANA-positive (M:F = 4:8) with a median titer of 1:100 (range, 1:100-1:800); 1 was transiently anti-dsDNA-positive. There were no significant differences between ANA-positive and ANA-negative donors in baseline demographics or pre-uninephrectomy creatinine clearance (median 108.0, range 79-179 mL/min vs. 106, range 58-172 mL/min, P = NS). Only 1 ANA-positive patient displayed transient microscopic hematuria (8 red blood cells); none had proteinuria pre-nephrectomy. Median follow-up was 63.5 (range, 21.2-139.3) months. At last clinic review, none of the ANA-positive donors had developed clinical symptoms or signs of SLE. Comparing ANA-positive and ANA-negative live donors at 5 years post-uninephrectomy, there were no significant differences in creatinine clearance (median 86.5, range 67-112 mL/min vs. 85.0, range 35-154 mL/min, P = NS), total urine protein (median 0, range 0-0.196 g/24 h vs 0, range 0-0.190 g/24 h, P = NS), or presence of hematuria (16.7% vs 33.3%, P = NS). Isolated ANA positivity does not contraindicate living kidney donation. Up to 5 years post- uninephrectomy, the risk of developing clinical lupus among low-titer ANA-positive individuals remains low. PMID:23726567

Lim, C C; Goh, A



Polychlorinated biphenyls, mercury, and antinuclear antibody positivity, NHANES 2003-2004.  


Serum antinuclear antibody positivity (ANA) has been associated with elevated serum polychlorinated biphenyls (PCBs) among residents in PCB-polluted areas; however, associations in general populations have not been reported by congener type or with adjustment for mercury. Cross-sectional data on serum PCBs, total blood mercury, ANA, and potential confounders age, race, body mass index, menopausal status, and dietary eicosapentaenoic acid (EPA) were obtained from the 2003-2004 National Health and Nutrition Examination Survey (NHANES) for males and females aged 12-85. PCB congeners were summed separately for dioxin-like and nondioxin-like PCBs; the former were weighted for toxic equivalent factors. Total PCBs by congener type and mercury were analyzed as both continuous log-transformed variables and as categorical quintiles. Logistic regression models were stratified by sex. There were no associations between nondioxin-like PCBs or mercury and ANA among males or females. Among females (n=114 affected and 518 unaffected), adjusting for potential confounders, the prevalence odds for ANA positivity were significantly elevated per incremental increase in log-transformed dioxin-like PCBs (odds ratio {OR}=1.66; 95% confidence interval {CI}=1.24, 2.23); the highest dioxin-like PCB quintile (>0.00425-0.04339ng/g) was significantly associated with 4.04 (95% CI=2.43, 6.70) greater prevalence odds for ANA positivity relative to the lowest quintile (Ptrend<0.001). We present novel findings of an association between low-level dioxin-like PCBs and ANA among women. No associations were observed between mercury and ANA at mercury levels common to the U.S. population. PMID:23419585

Gallagher, Carolyn M; McElroy, Anne E; Smith, Dylan M; Golightly, Marc G; Meliker, Jaymie R



Using the antinuclear antibody test to diagnose rheumatic diseases: when does a positive test warrant further investigation?  


The anti-nuclear antibody (ANA) test is ordered commonly as a screening test for rheumatic diseases. Although ANA positivity is highly sensitive for certain rheumatic diseases, the presence of ANA is nonspecific and can be associated with numerous nonrheumatic factors, including environmental exposures, malignancies, drugs, and infections. This article describes a practical approach for physicians when evaluating patients using a positive ANA test. In the absence of connective tissue disease symptoms, the ANA test has minimal clinical significance in diagnosing rheumatic diseases. Understanding how to use ANA test results appropriately may reduce unnecessary referrals and costly workups. PMID:22267099

Volkmann, Elizabeth R; Taylor, Mihaela; Ben-Artzi, Ami




Microsoft Academic Search

Objective: To study the correlation between enzyme linked immunosorbent assay (ELISA) and immunofluoresencent (IF) anti-dsDNA antibody measurement in different diseases. Patients: One hundred and forty sera from patients with systemic lupus erythematosus (SLE, n=40), rheumatoid arthritis (RA, n=30), disease control (n=40) and from healthy control subjects (n=30) were included. Results: Using the ELISA, serum anti-dsDNA was detected in 24\\/40 (60%)

Adel Alnaqdy; Juma Al-Busaidy; Batool Hassan



Detection of Specific Antinuclear Reactivities in Patients with Negative Anti-nuclear Antibody Immunofluorescence Screening Tests  

Microsoft Academic Search

Background: For detection of anti-nuclear antibodies (ANAs) and antibodies to extractable nuclear antigens (ENAs), samples frequently are screened with indirect immunofluorescence (IIF); further determination of anti-ENA antibodies is performed only when the result is positive. However, because anti-ENA reactivities are found in samples with low fluorescence intensities, we determined anti-ENA antibodies in samples with nega- tive IIF and thus calculated

Ilse E. A. Hoffman; Isabelle Peene; Eric M. Veys; Filip De Keyser


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



Circulating anti-nuclear antibodies in uveitis.  


Uveitis represents the inflammatory process of uvea being caused by an autoimmune mechanism. Similarly, systemic connective tissue diseases (CTDs) present as well an autoimmune pathogenesis and numerous are the reports of a correlated association of the two different conditions, according to their serological characteristics. In this work, we have studied a number of subjects affected by uveitis as well as a number of subjects affected by CTDs associated with uveitis (14.2%). Only one significant correlation has been observed here, and it is the one between uveitis and the Systemic Lupus Erythematosus (SLE, 42.8%). The observation has been made up to through a time-lapse of 18 months during which, the signs of uveitis showed a clear trend to faintly diminish till completely disappearing. At the same time, the presence of uveitis has not stressed out any correlation either with the general positivity for the autoantibodies, nor with the titration or the pattern of single fluorescent antibodies. This study seems to confirm the presence of a weak association between uveitis and CTDs (SLE excluded), where the research of antinuclear antibodies does not seem to give any useful element in terms of diagnostics and clinics, able to value the risk of developing CTDs when uveitis is already stated. PMID:23698221

Coaccioli, S; Di Cato, L; Panaccione, A; Crapa, M E; Paladini, A; Marinangeli, F



Prevalence and clinical significance of rare antinuclear antibody patterns.  


While some of the more frequent antinuclear (auto)antibodies (ANA) patterns such as homogenous nuclear staining have been extensively studied, the prevalence and clinical significance of rare antinuclear antibody patterns are not well understood. For the purpose of this review, we defined rare patterns as patterns occurring in less than 1% of patients that test positive on indirect immunofluorescence. The prevalence of different ANA patterns was determined in 68,128 consecutive patients who attended the outpatient clinic or were hospitalized at the University Hospitals Leuven over a 14-year period (1998-2011). To avoid bias, we only included the first sample for each patient and patients who tested positive in the period 1980-1997 were excluded. There were 9268 patients who tested positive for ANA. With the exception of the clinical association of anti-multiple nuclear dots (at higher titers) and anti-nuclear envelope autoantibodies with autoimmune liver disease, there was no good clinical association of rare ANA patterns with the diagnosis of auto-immune disorders. The most important non-autoimmune cause of rare ANA patterns was carcinoma, particularly in patients with rare cell-cycle related ANAs. PMID:23583982

Vermeersch, Pieter; Bossuyt, Xavier



Review for the generalist: The antinuclear antibody test in children - When to use it and what to do with a positive titer  

Microsoft Academic Search

The antinuclear antibody test (ANA) is a much overused test in pediatrics. The ANA does have a role in serologic testing but it should be a very limited one. It is often ordered as a screening test for rheumatic illnesses in a primary care setting. However, since it has low specificity and sensitivity for most rheumatic and musculoskeletal illnesses in

Peter N Malleson; Murray J Mackinnon; Michaela Sailer-Hoeck; Charles H Spencer



Analysis and significance of anti-nuclear antibodies in dogs  

Microsoft Academic Search

Assays for detecting and measuring antinuclear antibodies (ana) in dogs were compared. They included the indirect immunofluorescence test, using rat liver as substrate, and elisas for three nuclear antigens: double-stranded DNA, single-stranded dna and histone. There was no correlation between the ana titre and antibodies to the three nuclear antigens. Analysis of ana in different arthropathies showed no specific disease

D. F Kelly; S. D Carter



Protein-losing enteropathy associated with hypocomplementemia and anti-nuclear antibodies  

Microsoft Academic Search

:   We report a case of protein-losing enteropathy associated with an autoimmune disorder, presumably systemic lupus erythematosus.\\u000a Although typical manifestations of systemic lupus erythematosus were lacking, a high serum cholesterol level, a low serum\\u000a complement level, positivity for anti-nuclear antibody, and positivity for anti-single-strand DNA antibody suggested an autoimmune\\u000a mechanism as the cause of the condition. Although immunohistological examination of

Atsushi Nakajima; Shin Ohnishi; Toshihide Mimura; Kanae Kubo; Atsushi Suzuki; Yoshio Yazaki; Nobuyuki Matsuhashi



Ocular, systemic and antinuclear antibody changes with acebutolol  

PubMed Central

A group of 29 hypertensive patients were studied for side effects of acebutolol. An antinuclear antibody titre of ?1/64 developed in 23 per cent of patients during a 12-month course of treatment. Full ophthalmic examination before and after the treatment period showed a statistically significant increase in tear secretion at one year. One patient had a slight worsening of her psoriasis. No patients developed any symptoms or signs of oculomucocutaneous syndrome (OMCS) or systemic lupus erythematosus (SLE).

Hosie, James; Ghafoor, Salahudin Y. A.



Anti-nuclear envelope antibodies: Clinical associations  

Microsoft Academic Search

Objectives: Characterization of the clinical associations and clinical implications of antibodies reacting with antigens of the nuclear envelope. Methods: Description of an illustrative case and a MEDLINE search-assisted literature review of relevant cases. Results: With indirect immunofluorescence, autoantibodies directed against various antigens of the nuclear envelope stain the nucleus in a ring-like (rim) pattern. Autoantibodies against 5 antigenic components of

Gideon Nesher; Ruth Margalit; Yaacov J. Ashkenazi



Intracellular and circulating neuronal antinuclear antibodies in human epilepsy.  


There are overwhelming data supporting the inflammatory origin of some epilepsies (e.g., Rasmussen's encephalitis and limbic encephalitis). Inflammatory epilepsies with an autoimmune component are characterized by autoantibodies against membrane-bound, intracellular or secreted proteins (e.g., voltage gated potassium channels). Comparably, little is known regarding autoantibodies targeting nuclear antigen. We tested the hypothesis that in addition to known epilepsy-related autoantigens, the human brain tissue and serum from patients with epilepsy contain autoantibodies recognizing nuclear targets. We also determined the specific nuclear proteins acting as autoantigen in patients with epilepsy. Brain tissue samples were obtained from patients undergoing brain resections to treat refractory seizures, from the brain with arteriovenous malformations or from post-mortem multiple sclerosis brain. Patients with epilepsy had no known history of autoimmune disease and were not diagnosed with autoimmune epilepsy. Tissue was processed for immunohistochemical staining. We also obtained subcellular fractions to extract intracellular IgGs. After separating nuclear antibody-antigen complexes, the purified autoantigen was analyzed by mass spectrometry. Western blots using autoantigen or total histones were probed to detect the presence of antinuclear antibodies in the serum of patients with epilepsy. Additionally, HEp-2 assays and antinuclear antibody ELISA were used to detect the staining pattern and specific presence of antinuclear antibodies in the serum of patients with epilepsy. Brain regions from patients with epilepsy characterized by blood-brain barrier disruption (visualized by extravasated albumin) contained extravasated IgGs. Intracellular antibodies were found in epilepsy (n=13/13) but not in multiple sclerosis brain (n=4/4). In the brain from patients with epilepsy, neurons displayed higher levels of nuclear IgGs compared to glia. IgG colocalized with extravasated albumin. All subcellular fractions from brain resections of patients with epilepsy contained extravasated IgGs (n=10/10), but epileptogenic cortex, where seizures originated from, displayed the highest levels of chromatin-bound IgGs. In the nuclear IgG pool, anti-histone autoantibodies were identified by two independent immunodetection methods. HEp-2 assay and ELISA confirmed the presence of anti-histone (n=5/8) and anti-chromatin antibodies in the serum from patients with epilepsy. We developed a multi-step approach to unmask autoantigens in the brain and sera of patients with epilepsy. This approach revealed antigen-bound antinuclear antibodies in neurons and free antinuclear IgGs in the serum of patients with epilepsy. Conditions with blood-brain barrier disruption but not seizures, were characterized by extravasated but not chromatin-bound IgGs. Our results show that the pool of intracellular IgG in the brain of patients with epilepsy consists of nucleus-specific autoantibodies targeting chromatin and histones. Seizures may be the trigger of neuronal uptake of antinuclear antibodies. PMID:23880401

Iffland, Philip H; Carvalho-Tavares, Juliana; Trigunaite, Abhishek; Man, Shumei; Rasmussen, Peter; Alexopoulos, Andreas; Ghosh, Chaitali; Jørgensen, Trine N; Janigro, Damir



Detection of antinuclear antibodies by indirect immunofluorescence and by solid phase assay.  


Testing for antinuclear antibodies is useful for the diagnosis of systemic rheumatic diseases. Solid phase assays are increasingly replacing indirect immunofluorescence for detection of antinuclear antibodies. In the most recent generation of solid phase assays, manufacturers attempt to improve the performance of the assays by adding extra antigens. Solid phase assay (EliA CTD Screen, Phadia, in which antibodies to 17 antigens are detected) was compared to indirect immunofluorescence for the detection of antinuclear antibodies in diagnostic samples of 236 patients with autoimmune connective tissue diseases, in 149 healthy blood donors, 139 patients with chronic fatigue syndrome, and 134 diseased controls. The sensitivity of EliA CTD Screen for systemic lupus erythematosus, systemic sclerosis, primary Sjögren's syndrome, mixed connective tissue disease, and inflammatory myopathy was 74%, 72%, 89%, 100%, and 39%, respectively. The reactivity in blood donors, in patients with chronic fatigue syndrome, and in diseased controls was <4%. Likelihood ratios increased with increasing antibody concentrations. Generally, a positive test result by EliA CTD Screen had a higher likelihood ratio for systemic rheumatic disease than a positive test result by indirect immunofluorescence. A negative test result by indirect immunofluorescence, however, had a lower likelihood ratio than a negative test result by EliA CTD Screen, indicating that the negative predictive value was higher for indirect immunofluorescence than for EliA CTD screen. PMID:21741497

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



[Detection of anti-DNA antibodies by electroimmunodiffusion. Comparison of the results with the study of antinuclear factors by immunofluorescence].  


The detection of anti-DNA antibodies was carried out by the electroimmunodiffusion method. The results were compared to those of the immunofluorescent method for anti-nuclear factors. Positive results were obtained with the electroimmunodiffusion method in 86% of the lupus erythematosus cases, 77% of the sero-positive rhumatoid polyarthritis cases and 67% of the scleroderma cases. They are comparable to those obtained by other methods. The electroimmunodiffusion method allowed in 3 out of 54 sera to defect anti-DNA antibodies although no anti-nuclear factor was found. PMID:175459

Delpech, A; Delpech, B; Laumonier, R



Antinuclear antibodies in the sera of patients with nasopharyngeal carcinoma  

SciTech Connect

We studied the production of heterophile antinuclear antibodies (ANAs) in the sera of 50 patients, 20 with nasopharyngeal carcinoma (NPC) and 30 with other head and neck cancers (laryngeal cancer and maxillary cancer), before and after radiation therapy. A higher incidence of ANAs was found in the sera of patients with NPC and ANA production in these patients was higher after radiation therapy. We therefore performed in vitro experiments to explore the mechanisms of ANA production in the serum of postirradiated NPC patients. X-ray-irradiated NPC-derived cells (NPC-KT) produced a large amount of Epstein-Barr virus (NPC EBV) compared with non-irradiated NPC-KT cells. Nasopharyngeal carcinoma EBV-infected lymphocytes produced high levels of ANAs. These data suggest that lymphocytes infected by EBV from NPC cells may produce ANAs in the sera of NPC patients.

Takimoto, T.; Ishikawa, S.; Masuda, K.; Tanaka, S.; Yoshizaki, T.; Umeda, R. (Kanazawa Univ. (Japan))



The significance of IgM antinuclear antibody in rheumatoid arthritis and other connective tissue diseases  

Microsoft Academic Search

An investigation of the incidence of IgG and IgM antinuclear antibodies (ANA) in patients with connective tissue diseases showed that IgM ANA predominated in rheumatoid arthritis, whilst in systemic lupus erythematosus IgG antibodies were more common. Patients with other connective tissue diseases less frequently had antinuclear antibodies and there was little difference in the incidence of IgG and IgM antibodies.

M. C. Chellingworth; M. Salmon; D. L. Scott; P. A. Bacon



Molecular signatures of anti-nuclear antibodies—contribution of heavy chain framework residues  

Microsoft Academic Search

It is clear that besides the CDR residues, framework residues (particularly those on FR1 and FR3) can contribute towards antigen reactivity. This study was designed to compare the immunoglobulin heavy chain FR regions of anti-nuclear antibodies (comprised of 142 anti-ssDNA, 103 anti-dsDNA and 23 anti-nucleosome Abs) with those of non-nuclear antibodies (N=165), all drawn from the GenBank. The anti-nuclear antibodies

Peter Sedrak; Kelvin Hsu; Chandra Mohan



Sperm auto - antibodies and anti-nuclear antigen antibodies in chronic dioxin - exposed veterans  

Microsoft Academic Search

The authors studied anti-nuclear antibodies (ANA) in 25 chronic dioxin — exposed veterans by IIF technics with Hep-2 cell lilne and sperm autoantibodies by agglutination test of Franklin-Dukes. The site of antibody binding on spermatozoon is detected by IIF test.The control group for ANA detection is 63 healthy persons of the same age as that of dioxin — exposed veterans

Tran Thi Chinh; Phan Thi Phi Phi; Nguyen Thanh Thuy



Canine antinuclear antibodies: comparison of immunofluorescence staining patterns and precipitin reactivity.  


The occurrence of antinuclear antibodies (ANAs) against several specific nuclear antigens is clearly associated with certain systemic rheumatic disorders in human patients. Determination of ANAs on a routine basis, usually by indirect immunofluorescence (IIF) technique, has therefore become an important diagnostic tool. The subdividing of positive ANA-sera into different nuclear IIF staining patterns often gives clues to antibody specificity. The present investigation aimed at studying whether such subgroups of staining patterns in IIF ANA positive canine sera may represent certain specific ANAs that can be verified by standard methods used for specificity determination in humans. The presence of precipitating antibodies, determined by the Ouchterlony immunodiffusion (ID) technique, was found to be strictly associated with a positive IIF ANA, exhibiting a speckled staining pattern without any chromosomal reactivity. None of the sera with chromosomal reactivity contained precipitating antibodies. Among the ID positive serum samples, different antigenic reactivities were detected, represented by different ID subgroups. Only 1 of the 4 main subgroups obtained by ID showed identity with any of the common and disease-associated human ANA specificities, exhibiting anti-RNP reactivity. One of these serum samples concomitantly exhibited precipitating antibodies against the Sm antigen. PMID:10605137

Hansson, H; Karlsson-Parra, A



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.



A case of anti-nuclear antibody negative systemic lupus erythematosus associated with penile ulcer  

Microsoft Academic Search

We report here an old male patient with anti-nuclear antibody (ANA) negative systemic lupus erythematosus (SLE) with active renal disease and penile ulcer. He revealed nephrotic syndrome, malar rash and oral ulcer. SLE was discussed, however both ANA and anti-DNA antibody were persistently negative. A penile ulcer was also observed. He died of acute respiratory distress. Autopsy findings including onion

H. Osawa; H. Yamabe; K. Ozawa; K. Fukushi; H. Inuma; M. Miyata; S. Seino; T. Sasaki; S. Yoshikawa; M. Kaizuka; N. Tamura; K. Nomura; Y. Kamata; K. Onodera



Anti-neutrophil cytoplasm antibodies (ANCA) in rheumatoid arthritis: relationship to HLA-DR phenotypes, rheumatoid factor, anti-nuclear antibodies and disease severity  

Microsoft Academic Search

To investigate a possible relationship between the presence of anti-neutrophil cytoplasm antibodies (ANCA), rheumatoid factors (RF), anti-nuclear antibodies (ANA), disease severity and HLA-DR phenotypes, 46 consecutive ANCA+ and 48 ANCA-, clinically well-documented RA patients were studied for RF, ANA and HLA-DR phenotypes. The 46 ANCA+ patients showed predominantly an atypical perinuclear staining pattern (89%). ANCA positivity was associated with higher

E. Röther; D. Metzger; B. Lang; I. Melchers; H.-H. Peter



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



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


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. PMID:24031110

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



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



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



21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2010 CFR

...immunochemical techniques the autoimmune antibodies in serum, other...erythematosus (a multisystem autoimmune disease in which antibodies attack the...tissues), hepatitis (a liver disease), rheumatoid...



21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2010 CFR

...immunochemical techniques the autoimmune antibodies in serum, other...erythematosus (a multisystem autoimmune disease in which antibodies attack the...tissues), hepatitis (a liver disease), rheumatoid...



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


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



New Methods for Detection of Anti-nuclear Antibodies  

Microsoft Academic Search

Many different autoantibodies which react with a variety of different nuclear and cytoplasmic antigens have been described. Detection of some these antibodies has been shown to be clinically useful in a number of different autoimmune diseases. For many years, the detection of most of the clinically relevant antibodies was done with by immunofluorescence on tissue substrates and human cultured cell

Linda Cook



21 CFR 866.5100 - Antinuclear antibody immunological test system.  

Code of Federal Regulations, 2013 CFR

...of systemic lupus erythematosus (a multisystem autoimmune disease in which antibodies attack the victim's own tissues), hepatitis (a liver disease), rheumatoid arthritis, Sjögren's syndrome (arthritis with inflammation of the eye, eyelid,...



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...



Comparison of Antinuclear Antibody Testing Methods: Immunofluorescence Assay versus Enzyme Immunoassay  

Microsoft Academic Search

Performances of anti-nuclear antibody testing by immunofluorescence assay (ANA-IFA) and enzyme immu- noassay (ANA-EIA) were compared in relation to patient diagnosis. A total of 467 patient serum samples were testedbyANA-IFA(Kallestad;Sanofi)andANA-EIA(RADIAS;Bio-Rad),andtheirage,sex,diagnosis,disease status, and medications were obtained through chart review. Reference ranges were established by testing 98 healthy blood donor samples. Eighty-six samples came from patients with diffuse connective tissue diseases, including




Exposure of HEp2 Cells to Stress Conditions Influences Antinuclear Antibody Reactivity  

Microsoft Academic Search

This study of stress-related antinuclear antibody (ANA) reactivity was undertaken with the objective of improving clinical ANA testing. ANA was determined by parallel enzyme-linked immunosorbent assays of crude nuclear protein antigen extracted from HEp-2 cells either grown under optimal conditions (providing nonstress ANA antigen) or exposed to stress (providing stress ANA antigen). The stress stimuli used were gamma radiation (causing

Liping Du; Sachiko Fukushima; Annahita Sallmyr; Rolf Manthorpe; Anders Bredberg



A semiquantitative measurement of anti-nuclear antibody using immuno-microfluorimetry  

Microsoft Academic Search

1.Using microfluorimetry, the strength of fluorescence was measured on fluoresceinated anti-nuclear antibody of SLE sera. The indirect “Sandwich” method was applied using human peripheral lymphocytes as substrates tissue.2.The results of using three FITC-labelled anti-human IgG conjugates of different types were compared with each other.3.More specific and more consistent results were obtained with conjugates with a lower F\\/P ratio and lower

Hiroaki Ueki; Itaru Yoskii; Akira Ikeda; Nozomi Nohara



Anti-nuclear antibodies and the optic-spinal form of multiple sclerosis  

Microsoft Academic Search

We found anti-nuclear antibodies (ANA) (1?:?20 or higher) in sera from 11 of 16 patients with a diagnosis of the optic-spinal\\u000a form of multiple sclerosis (OpS-MS) and 13 of 59 patients with other forms of MS (other MS), both rates being significant\\u000a (P = 0.0004). Six of the OpS-MS patients had a high level of ANA (1?:?80 or higher), while

Toshiyuki Fukazawa; Seiji Kikuchi; Hidenao Sasaki; Koji Hamada; Takeshi Hamada; Kazuo Miyasaka; Kunio Tashiro



Reactive nitrogen intermediates, antinuclear antibodies and copper-thionein in serum of patients with rheumatic diseases  

Microsoft Academic Search

Sera from 354 patients with various inflammatory and autoimmune rheumatic diseases were screened for the presence of reactive nitrogen intermediates, antinuclear antibodies and the antioxidase copper-thionein (Cu-thionein), and compared to sera from healthy donors and patients with non-rheumatic diseases including AIDS, various internal as well as neurological diseases and carcinoma of different organs. When compared to healthy individuals, the levels

R. Miesel; M. Zuber



Detection of perinuclear antineutrophil cytoplasmic antibodies and antinuclear antibodies in the diagnosis of canine inflammatory bowel disease.  


In recent years, serologic markers for diagnosis and classification of inflammatory bowel disease (IBD) have been used in human medicine. Perinuclear, antineutrophil, cytoplasmic antibodies (p-ANCA) are the most important of these markers. Because of their similar pattern of fluorescence, antinuclear antibodies (ANA) could cause misleading interpretations. The aim of the present study was to evaluate the use of an indirect fluorescent antibody test to detect p-ANCA in dogs with IBD, to compare the presence of p-ANCA in dogs with IBD with the presence of the same antibodies in other dogs, and to analyze the presence of ANAs in the p-ANCA-positive samples. Using a 110 dilution as a cutoff point, a sensitivity of 0.34 and a specificity of 0.86 was obtained when dogs with IBD were compared with the other groups as a whole, and specificity increased to 0.94 when dogs with IBD were compared with animals with other chronic gastrointestinal disorders. The lowest specificity value, 0.76, was obtained when the group of dogs with IBD was compared with that of dogs with different inflammatory and infectious disorders. Globally, 78 dogs were positive for p-ANCA when the cutoff was 110. Only 1 dog from these 78 animals was also seropositive to ANA. The results suggest that 1) detection of p-ANCA might be included in the IBD diagnostic protocol as another test to differentiate between this disease and other digestive diseases with similar clinical signs, and 2) most p-ANCA-positive dogs are not ANA positive. PMID:20622225

Mancho, Carolina; Sainz, Angel; García-Sancho, Mercedes; Villaescusa, Alejandra; Tesouro, Miguel A; Rodríguez-Franco, Fernando



Clinical significance of antinuclear matrix antibody in serum from patients with anti-U1RNP antibody  

Microsoft Academic Search

\\u000a Abstract Serum containing anti-U1RNP antibodies reacts with the nuclear matrix, the relatively insoluble component of the cell nucleus,\\u000a in addition to U1RNP. In this study, we determine the serum titer and clinical correlations of antinuclear matrix antibodies\\u000a in samples from patients with anti-U1RNP antibodies. The patients with anti-U1RNP antibodies were classified as having mixed\\u000a connective tissue disease (MCTD, 15 patients),

Shinichi Sato; Minoru Hasegawa; Hironobu Ihn; Kanako Kikuchi; Kazuhiko Takehara



Analysis of 15 patients with systemic lupus erythematosus manifesting with negative immunofluorescence anti-nuclear antibodies after treatment.  


The purpose of this study was to investigate the clinical and laboratorial characteristics of patients with systemic lupus erythematosus (SLE) manifesting with negative immunofluorescence anti-nuclear antibodies (IFANA) after treatment for the better understanding of negative conversion of IFANA. Demographic characteristics, clinical and laboratory data of hospitalized SLE patients between March 2006 and May 2011 were retrospectively reviewed. Fifteen cases with negative IFANA were identified in 960 patients. All of the 15 patients were severe, 11 patients manifested with nephritic range proteinuria and hypoalbuminemia, 8 patients were complicated with severe infection and all of the patients had been treated with glucocorticoid and immunosuppressant. Anti-ENA antibodies were positive in 4 of 15 patients. Eight patients died after average 1-year follow-up. Collectively, negative IFANA is mainly attributed to nephritic-range proteinuria; and large-dose glucocorticoid, immunosuppressant and severe infection are also important factors for negative IFANA. Antinuclear antibody can be detected in some SLE patients with negative IFANA by changing the detection method and titer. Negative conversion of IFANA often indicates unfavorable prognosis for severe patients. PMID:22187164

Song, L-J; Ding, F; Liu, H-X; Shu, Q; Yu, X; Li, J; Li, X-F



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



Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study  

Microsoft Academic Search

Primary biliary cirrhosis (PBC) sera contain antibodies which recognize various nuclear envelope proteins of which antibody against gp210 has been proven to be diagnostic for disease. In contrast, the clinical significance of another nuclear envelope antibody, anti-p62 antibody has not been well investigated. In the present study, we have analyzed anti-nuclear envelope antibodies by indirect immunofluorescence and immunoblot using rat

Kiyomitsu Miyachi; Raleigh W. Hankins; Hiroshi Matsushima; Futoshi Kikuchi; Tetushi Inomata; Tuneyoshi Horigome; Minoru Shibata; Yasushi Onozuka; Yukihisa Ueno; Etsuko Hashimoto; Naoaki Hayashi; Akitaka Shibuya; Shuichi Amaki; Hiroshi Miyakawa



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

PubMed Central

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 for comprehensive immunofluorescence analyses. The immunofluorescence pattern of human anti?proteasome antibodies was compared with a panel of monoclonal and polyclonal reference antibodies, and colocalisation was analysed using confocal microscopy. Results Anti?proteasome antibodies clearly contributed to the ANA patterns of their respective serum samples from patients with different rheumatic disorders. In addition to the nuclear pattern, proteasomal staining was also detectable in the cytoplasm, at the endoplasmic reticulum and perinuclear regions showing features overlapping with other known autoantibodies such as those to mitochondria. The specificity of anti?proteasome antibodies was proved by competition experiments and by colocalisation with monoclonal reference antibodies in confocal microscopy. Conclusion In ANA diagnostics, interference of anti?proteasome antibodies will have to be taken into account, especially in the differentiation of anti?cytoplasmatic autoantibodies.

Feist, E; Brychcy, M; Hausdorf, G; Hoyer, B; Egerer, K; Dorner, T; Kuckelkorn, U; Burmester, G-R



Prevalence and Sociodemographic Correlates of Antinuclear Antibodies In the United States  

PubMed Central

Objective To estimate the prevalence, types and sociodemographic and biobehavioral correlates of antinuclear antibodies (ANA) in the United States (U.S.). Methods Cross-sectional analysis of 4,754 individuals from the National Health and Nutrition Examination Survey (NHANES) 1999–2004. ANA by indirect immunofluorescence, including cellular staining patterns and specific autoantibody reactivities by immunoprecipitation in those with ANA. Results ANA prevalence in the U.S. population ages 12 years and older was 13.8% (95% CI, 12.2% to 15.5%). ANA increased with age (P = 0.01) and were more prevalent among females than males (17.8% vs. 9.6%, P < 0.001), with the female to male ratio peaking at 40–49 years of age. ANA prevalence was modestly higher in African Americans than whites (adjusted prevalence odds ratio [POR], 1.30; 95% CI, 1.00 to 1.70). Remarkably, ANA were less common in overweight and obese (adjusted POR, 0.74; 95% CI, 0.59 to 0.94) individuals than persons of normal weight. No significant associations were seen with education, family income, alcohol use, smoking history, serum levels of cotinine or C-reactive protein. In ANA-positive individuals, nuclear patterns were seen in 84.6%, cytoplasmic patterns in 21.8%, and nucleolar patterns in 6.1%, and the most common specific autoantibodies were anti-Ro (3.9%) and anti-Su (2.4%). Conclusion These findings suggest that over 32 million persons in the U.S. have ANA and the prevalence is higher among females, older individuals, African Americans and those with normal weight. These data will serve as a useful baseline for future investigations of predictors and changes in ANA prevalence over time.

Satoh, Minoru; Chan, Edward K. L.; Ho, Lindsey A.; Rose, Kathryn M.; Parks, Christine G.; Cohn, Richard D.; Jusko, Todd A.; Walker, Nigel J.; Germolec, Dori R.; Whitt, Irene Z.; Crockett, Patrick W.; Pauley, Brad A.; Chan, Jason Y.F.; Ross, Steven J.; Birnbaum, Linda S.; Zeldin, Darryl C.; Miller, Frederick W.



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



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

Microsoft Academic Search

BACKGROUND: In Plasmodium falciparum-infected children, the relationships between blood cell histopathology, blood plasma components, development of immunocompetence and disease severity remain poorly understood. Blood from Nigerian children with uncomplicated malaria was analysed to gain insight into these relationships. This investigation presents evidence for circulating neutrophil extracellular traps (NETs) and antinuclear IgG antibodies (ANA). The presence of NETs and ANA to

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



Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists.  


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. PMID:10799458

James, K; Carpenter, A B; Cook, L; Marchand, R; Nakamura, R M



Reconstructing a 3-dimensional image of the results of antinuclear antibody testing by indirect immunofluorescence.  


Indirect immunofluorescence anti-nuclear antibody testing (IIF-ANAT) is an essential screening tool in the diagnosis of various autoimmune disorders. ANA titer quantification and interpretation of immunofluorescence patterns are determined subjectively, which is problematic. First, we determined the examination conditions under which IIF-ANAT fluorescence intensities are quantified. Next, IIF-ANAT was performed using homogeneous, discrete speckled, and mixed serum samples. Images were obtained using Bio Zero BZ-8000, and 3-dimensional images were reconstructed using the BZ analyzer software. In the 2-dimensional analysis, homogeneous ANAs hid the discrete speckled pattern, resulting in a diagnosis of homogeneous immunofluorescence. However, 3-dimensional analysis of the same sample showed discrete speckled-type ANA in the homogeneous background. This study strengthened the current IIF-ANAT method by providing a new approach to quantify the fluorescence intensity and enhance the resolution of IIF-ANAT fluorescence patterns. Reconstructed 3-dimensional imaging of IIF-ANAT can be a powerful tool for routine laboratory examination. PMID:23073364

Murai, Ryosei; Yamada, Koji; Tanaka, Maki; Kuribayashi, Kageaki; Kobayashi, Daisuke; Tsuji, Naoki; Watanabe, Naoki



The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis  

PubMed Central

Background Systemic sclerosis (SSc) is a connective tissue disorder with excessive fibrosis of the skin and various internal organs. Although SSc is a heterogeneous disease, it has been reported that the particular antinuclear antibodies (ANA) are often indicative of clinical features, disease course and overall severity. Objective To clarify the association of clinical and prognostic features with serum ANA in Japanese patients with SSc. Methods We studied 203 Japanese patients diagnosed with SSc, who visited our hospital during the period 1983–2005. Six SSc-related ANA were identified using indirect immunofluorescence, double immunodiffusion and immunoprecipitation assays. Results Patients with SSc were classified into six ANA-based subgroups and a group without ANA. As expected, antitopoisomerase I antibody (Ab, n = 64), anti-RNA polymerases (RNAP) Ab (n = 12) and anti-U3 RNP Ab (n = 5) were associated with diffuse cutaneous SSc, whereas anticentromere Ab (ACA, n = 75), anti-Th/To Ab (n = 7) and anti-U1 RNP Ab (n = 10) were frequently detected in patients with limited cutaneous SSc. Clinical features of the ANA-negative group (n = 10) were heterogeneous. Consistent with previous findings in Caucasian and/or black African patients, antitopoisomerase I Ab was associated with the involvement of vascular and pulmonary fibrosis, leading to decreased survival rate. However, no patients with anti-RNAP Ab developed renal crisis and the frequency of isolated pulmonary hypertension in patients with ACA, anti-Th/To Ab or anti-U3 RNP Ab was similar to that in other ANA-based subgroups. Conclusion These results indicate that the clinical relevance of SSc-related ANA in Japanese patients differs in some aspects from that in Caucasian and/or black African patients.

Hamaguchi, Y; Hasegawa, M; Fujimoto, M; Matsushita, T; Komura, K; Kaji, K; Kondo, M; Nishijima, C; Hayakawa, I; Ogawa, F; Kuwana, M; Takehara, K; Sato, S



Differential induction of lupus associated antinuclear antibodies in MRL mice by monoclonal anti-Sm antibodies.  


The effect of monoclonal autoantibodies on immunoregulation was investigated in MRL/MpJ-lpr/lpr mice. Passive transfer of KSm2 (a monoclonal IgG2a antibody directed against the 16 kD polypeptide of Sm) induced IgG antibodies to the other major immunoreactive polypeptides of Sm (28 and 29 kD) in all mice studied, and to polypeptides of the closely related antigen nRNP/Sm in 63% of the mice. In addition an increment in IgG anti-dsDNA antibodies, and in IgA and IgM anti-Sm antibodies, over control levels was observed. These effects were not due to polyclonal activation since anti-histone antibody levels were unaffected. Two other IgG2a monoclonal antibodies: KSm5 (directed against the 28 and 29 kD Sm polypeptides) and OX 12 (directed against an irrelevant antigen) failed to modulate the autoimmune responses of the mice in any way. These results demonstrate specific antibody-mediated connectivity between B cell clones producing autoantibodies against three distinct antigens. PMID:3496996

Stocks, M R; Williams, D G; Maini, R N



Prospective cohort study of effects of infliximab on rheumatoid factor, anti-cyclic citrullinated peptide antibodies and antinuclear antibodies in patients with long-standing rheumatoid arthritis  

Microsoft Academic Search

BackgroundAntibodies to cyclic citrullinated peptide (anti-CCP) and IgM rheumatoid factor (IgM-RF) are well-established serological markers for rheumatoid arthritis (RA). Lupus-like disease with antinuclear antibodies (ANA) has been reported during TNF? antagonist therapy. Our objectives were to investigate the effect of infliximab therapy on these three autoantibodies in patients with established RA and to look for correlations linking IgM-RF and anti-CCP

Alexandra Bruns; Pascale Nicaise-Roland; Gilles Hayem; Elisabeth Palazzo; Philippe Dieudé; Sabine Grootenboer-Mignot; Sylvie Chollet-Martin; Olivier Meyer



Olf1/EBF associated zinc finger protein interfered with antinuclear antibody production in patients with systemic lupus erythematosus  

PubMed Central

Introduction The aim of the study was to determine whether Olf1/EBF associated zinc finger protein (OAZ), a transcription factor encoded by a positional systemic lupus erythematosus (SLE) candidate gene, plays a functional role in the pathogenesis in SLE. Methods Gene expression levels in peripheral blood cells (PBLs) measured using quantitative real-time polymerase chain reaction (qPCR) were assessed for association with disease activity and the presence of specific autoantibodies. Peripheral blood mononuclear cells (PBMCs) were incubated with specific siRNAs for three days, then cells were harvested for measuring mRNA levels using qPCR, and supernatants for levels of total immunoglobulin (Ig)G and IgM as well as secreted cytokines, chemokine and antinuclear antibodies (ANA) using ELISA. Indirect immunofluorescence was also applied for ANA detection. Results OAZ gene expressions in PBLs from 40 ANA-positive SLE patients were significantly increased than those from 30 normal controls (P < 0.0001) and 18 patients with rheumatoid arthritis (P < 0.01). In SLE patients, OAZ transcripts were positively correlated with SLE disease activity index (SLEDAI) score (r = 0.72, P < 0.0001) and higher in those positive for anti-dsDNA or anti-Sm antibodies (both P < 0.05). Co-culturing with OAZ siRNAs reduced mRNA levels of OAZ by 74.6 ± 6.4% as compared to those co-cultured with non-targeting siRNA and OAZ silencing resulted in reduced total IgG, ANA, interferon (IFN)-?, interleukin (IL)-10, IL-12 and IL-21, but elevated CCL2 levels in culture supernatants (P < 0.05). The declined ANA levels correlated with inhibited OAZ expression (r = 0.88, P = 0.05), reduced IL-21 levels (r = 0.99, P < 0.01), and elevated chemokine (C-C motif) ligand 2 levels (r = -0.98, P < 0.01). Expressions of ID1-3 were significantly down-regulated by 68.7%, 70.2% and 67.7% respectively after OAZ silence, while ID3 was also highly expressed in SLE PBLs (P < 0.0001) and associated with disease activity (r = 0.76, P < 0.0001) as well as anti-dsDNA or anti-Sm antibodies (both P < 0.05). Conclusions Elevated expression of OAZ transcripts in SLE PBLs were strongly correlated with disease activity. Suppression of OAZ expression inhibited downstream ID levels, and secretion of ANA and IL-21, implicating a role of OAZ pathway in the pathogenesis of SLE.



Anti-SS-A\\/Ro antibody determination by indirect immunofluorescence and comparison of different methods of anti-nuclear antibody screening  

Microsoft Academic Search

We evaluated the utility of HEp-2 cells transfected with the 60 kDa SS-A\\/Ro as a substrate for indirect immunofluorescence\\u000a (IIF-HEp-2000) to compare several methods for screening Japanese serum samples for anti-SS-A\\/Ro antibodies. Serum samples\\u000a from 243 Japanese patients were analyzed by IIF for anti-nuclear antibodies (ANAs), using HEp-2 cells (IIF-HEp-2), and for\\u000a anti-SS-A\\/Ro 60 kDa antibodies, using IIF-HEp-2000 and enzyme-linked immunosorbent assay

Noriyo Tanaka; Yoshinao Muro; Kazumitsu Sugiura; Yasushi Tomita



Update on Anti-Saccharomyces cerevisiae antibodies, anti-nuclear associated anti-neutrophil antibodies and antibodies to exocrine pancreas detected by indirect immunofluorescence as biomarkers in chronic inflammatory bowel diseases: Results of a multicenter study  

Microsoft Academic Search

AIM: Anti-Saccharomyces cerevisiae antibodies (ASCA), anti-nuclear associated anti-neutrophil antibodies (NANA) and antibodies to exocrine pancreas (PAB), are serological tools for discriminating Crohn's disease (CrD) and ulcerative colitis (UC). Like CrD, coeliac disease (CoD) is an inflammatory bowel disease (IBD) associated with (auto) antibodies. Performing a multicenter study we primarily aimed to determine the performance of ASCA, NANA and PAB tests

S Desplat-Jégo; C Johanet; A Escande; J Goetz; N Fabien; N Olsson; E Ballot; J Sarles; JJ Baudon; JC Grimaud; M Veyrac; P Chamouard; RL Humbel


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



Uveitis and Anti Nuclear Antibody Positivity in Children with Juvenile Idiopathic Arthritis  

Microsoft Academic Search

This study was conducted to determine the frequency of antinuclear antibodies (ANA) positivity and uveitis in our newly diagnosed juvenile idiopathic arthritis (JIA) patients classified according to International League Against Rheumatology (ILAR) classification criteria. Ninety-two girls and 106 boys, totally 198 children were enrolled in the study. of them 36 (18.2%) were found to be ANA positive. Chronic anterior uveitis

Özgür Kasapçopur; Nail Yologlu; Yilmaz Özyazgan; Gökmen Ercan; Salim Çaliskan; Lale Sever; Huri Özdogan; Nil Arisoy



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


Apolipoprotein E-knockout (ApoE(-/-)) mice, atherosclerosis-prone mice, show an autoimmune response, but the pathogenesis is not fully understood. We investigated the pathogenesis in female and male ApoE(-/-) mice. The spleens of all ApoE(-/-) 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(-/-) mice after 4weeks of lipopolysaccharide (LPS), Toll-like receptor 4 ligand, administration. ApoE(-/-) 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(-/-) than B6 mice. The expression of TLR4, MyD88, IRF3, pp38, and Bax differed by sex in ApoE(-/-) 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(-/-) mice. PMID:22713470

Wang, Yuehai; Huang, Ziyang; Lu, Huixia; Lin, Huili; Wang, Zhenhua; Chen, Xiaoqing; Ouyang, Qiufang; Tang, Mengxiong; Hao, Panpan; Ni, Jingqin; Xu, Dongming; Zhang, Mingxiang; Zhang, Qunye; Lin, Ling; Zhang, Yun



TLR Tolerance Reduces IFN-Alpha Production Despite Plasmacytoid Dendritic Cell Expansion and Anti-Nuclear Antibodies in NZB Bicongenic Mice  

Microsoft Academic Search

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL\\/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.NZBc13) intervals develop anti-nuclear antibodies and mild glomerulonephritis (GN), together with increased T and B cell activation. Here, we produced B6.NZBc1c13

Evelyn Pau; Yui-Ho Cheung; Christina Loh; Ginette Lajoie; Joan E. Wither



Clinical significance of low titer anti-nuclear antibodies in early rheumatoid arthritis: implications on the presentation and long-term course of the disease  

Microsoft Academic Search

The objective of this study was to evaluate the clinical significance of anti-nuclear antibodies (ANA) detected in the early\\u000a stages of rheumatoid arthritis (RA), by a retrospective comparison of the clinical, laboratory, and therapeutic characteristics\\u000a of patients with or without ANA. The files of 99 longstanding seropositive RA patients were reviewed. Data relating to demographics,\\u000a medical history, family history, physical

Dan Caspi; Ori Elkayam; Miruna Eisinger; Nurit Vardinon; Michael Yaron; Michael Burke



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


Antinuclear Antibodies and Patterns of Nuclear Immunofluorescence in Type 1 Autoimmune Hepatitis  

Microsoft Academic Search

To determine the significance of antinuclearantibodies and their patterns of indirectimmunofluorescence in type 1 autoimmune hepatitis, serafrom 99 patients were evaluated. Patients withantinuclear antibodies had a lower frequency of livertransplantation (6% vs 22%, P = 0.04) than seronegativepatients. They were also more commonly HLA-DR4- positivethan seronegative patients (56% vs 30%, P = 0.05) and normal subjects (56% vs 30%, P

Albert J. Czaja; Fabio Cassani; Michela Cataleta; Paolo Valentini; Francesco B. Bianchi



The origin of anti-nuclear antibodies in bcl-2 transgenic mice  

Microsoft Academic Search

bcl-2 transgenic mice develop anti-double-stranded (ds) DNA antibodies similar to those present in systemic lupus erythematosus. To begin to understand where a breakdown in the regulation of autoreactive lymphocytes is occurring, we have used a bcl-2 transgene (Tg) in conjunction with an Ig Tg that allows us to identify and track anti-dsDNA B cells. Previously, we have shown that anti-

Laura Mandik-Nayak; Sudhir Nayak; Caroline Sokol; Ashlyn Eaton-Bassiri; Michael P. Madaio; Andrew J. Caton; Jan Erikson



TLR Tolerance Reduces IFN-Alpha Production Despite Plasmacytoid Dendritic Cell Expansion and Anti-Nuclear Antibodies in NZB Bicongenic Mice  

PubMed Central

Genetic loci on New Zealand Black (NZB) chromosomes 1 and 13 play a significant role in the development of lupus-like autoimmune disease. We have previously shown that C57BL/6 (B6) congenic mice with homozygous NZB chromosome 1 (B6.NZBc1) or 13 (B6.NZBc13) intervals develop anti-nuclear antibodies and mild glomerulonephritis (GN), together with increased T and B cell activation. Here, we produced B6.NZBc1c13 bicongenic mice with both intervals, and demonstrate several novel phenotypes including: marked plasmacytoid and myeloid dendritic cell expansion, and elevated IgA production. Despite these changes, only minor increases in anti-nuclear antibody production were seen, and the severity of GN was reduced as compared to B6.NZBc1 mice. Although bicongenic mice had increased levels of baff and tnf-? mRNA in their spleens, the levels of IFN-?-induced gene expression were reduced. Splenocytes from bicongenic mice also demonstrated reduced secretion of IFN-? following TLR stimulation in vitro. This reduction was not due to inhibition by TNF-? and IL-10, or regulation by other cellular populations. Because pDC in bicongenic mice are chronically exposed to nuclear antigen-containing immune complexes in vivo, we examined whether repeated stimulation of mouse pDC with TLR ligands leads to impaired IFN-? production, a phenomenon termed TLR tolerance. Bone marrow pDC from both B6 and bicongenic mice demonstrated markedly inhibited secretion of IFN-? following repeated stimulation with a TLR9 ligand. Our findings suggest that the expansion of pDC and production of anti-nuclear antibodies need not be associated with increased IFN-? production and severe kidney disease, revealing additional complexity in the regulation of autoimmunity in systemic lupus erythematosus.

Loh, Christina; Lajoie, Ginette; Wither, Joan E.



Gender differences in the relationship of anti-parvovirus B19 IgG with antinuclear antibody and C-reactive protein in clinical adult serum samples  

Microsoft Academic Search

Human parvovirus B19 (B19) infection is often suspected as an etiologic agent in a variety of rheumatologic diseases. It has\\u000a been hypothesized that this virus potentially induces immune dysregulation by abnormal cytokine expression in susceptible\\u000a hosts. The objective of this study is to examine the relationship between anti-parvovirus B19 IgG antibody (B19 IgG) and two\\u000a common markers of immune dysregulation—antinuclear

Thomas A. O’Bryan



Epitope-specific anti-nuclear antibodies are expressed in a mouse model of primary biliary cirrhosis and are cytokine-dependent.  


Although the hallmark of primary biliary cirrhosis (PBC) is the presence of anti-mitochondrial antibodies (AMA), a significant number of patients have anti-nuclear antibodies (ANA) directed primarily against two nuclear proteins, gp210 and sp100. In PBC, there are considerable data on the specificity of these anti-nuclear antibodies as well as suggestive evidence that antibodies to gp210 predict a poor outcome. However, a further understanding of the significance of these autoantibodies has been hampered by limitations in accessing human subjects in a preclinical or early asymptomatic stage. To overcome this limitation, we have taken advantage of transgenic mice with abrogated transforming growth factor-? signalling in T cells (dnTGF-?RII) that develop histological features of PBC as well as the same AMA specificity. We studied these mice for serum ANA, including specific autoantibodies against gp210 and sp100. We further examined sera from dnTGF-?RII mice with concurrent deletions of the genes encoding interleukin (IL)-12p35, IL-12p40, IL-23p19, IL-17, IL-6, interferon (IFN)-? or tumour necrosis factor (TNF)-?. Sera from all the dnTGF-?RII mouse lines contained antibodies against gp210 and sp100. Of significance, mice with germline deletions of the genes encoding IL-12p40, IL-23p19, IL-17, IL-6 and TNF-? had significantly lower titres of anti-gp210 antibodies. These results provide a platform to dissect the mechanisms of gp210 and sp100 autoantibody production in dnTGF-?RII mice as well as to study the possible role of ANA in the pathophysiology of PBC. PMID:22519587

Yang, C-Y; Leung, P S C; Yang, G-X; Kenny, T P; Zhang, W; Coppel, R; Norman, G L; Ansari, A A; Mackay, I R; Worman, H J; Gershwin, M E



Differences in individual efficacy of two Sairei-to preparations (Sojyutu-Sairei-to and Byakujyutu-Sairei-to) on recurrent spontaneous abortions of autoimmune etiologies evaluated by antinuclear antibody and anticardiolipin antibody titers.  


The differences in individual efficacy of two Sairei-to preparations (Sojyutu-Sairei-to and Byakujyutu-Sairei-to) on antinuclear antibody (ANA) and anticardiolipin antibody (ACLA) positive recurrent spontaneous abortion (RSA) was analyzed in 52 patients (a total of 61 treatment sessions). Patients who failed to respond to initial treatment with Sojyutu-Sairei-to were additionally treated with Byakujyutu- Sairei-to, and the time course of ANA and ACLA titers in these patients was analyzed. ACLA titers were decreased significantly by the treatment of Byakujyutu-Sairei-to, however, the percentage of successfully prevented abortion cases did not differ significantly between the Sojyutu-Sairei-to treatment group and the Byakujyutu-Sairei-to treatment group. ACLA titer was decreased in all 10 cases where abortion was successfully prevented by the treatment with Sojyutu-Sairei-to or Byakujyutu-Sairei-to. In the cases where both ANA and ACLA were decreased following treatment with Sojyutu-Sairei-to or Byakujyutu-Sairei-to, the percentage of cases rated as "Kyo" and "Rikan" were significantly higher in the Byakujyutu-Sairei-to group. These results indicate that Byakujyutu-Sairei-to is effective against ACLA positive RSA through the antibody-reducing activity, which differs from that of Sojyutu-Sairei-to in individual cases. On the basis of these results, Sairei-to therapy, which is superior to aspirin and heparin in terms of efficacy and safety, is recommended as the first-line therapy for RSA of autoimmune etiologies. Furthermore, to elevate the percentage of successfully prevented abortions, it is advisable to select one of the two Sairei-to preparations (Sojyutu-Sairei-to and Byakujyutu-Sairei-to) on the basis of differential diagnosis using the methods of Oriental medicine. PMID:20128042

Kano, Takashi; Shimizu, Masahiko; Kanda, Takayoshi



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  

PubMed Central

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 blood parameters in two types of experiments: ‘placebo-controlled double blind’ experiment for shorter duration and ‘uncontrolled verum fed experiment’ for longer duration. Positive modulation of ANA titer was observed along with changes in certain relevant hematological parameters, namely total count of red blood cells and white blood cells, packed cell volume, hemoglobin content, erythrocyte sedimentation rate and blood sugar level, mostly within 2 months of drug administration. Thus, Arsenicum album appears to have great potential for ameliorating arsenic induced elevated ANA titer and other hematological toxicities.

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



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.  


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 blood parameters in two types of experiments: 'placebo-controlled double blind' experiment for shorter duration and 'uncontrolled verum fed experiment' for longer duration. Positive modulation of ANA titer was observed along with changes in certain relevant hematological parameters, namely total count of red blood cells and white blood cells, packed cell volume, hemoglobin content, erythrocyte sedimentation rate and blood sugar level, mostly within 2 months of drug administration. Thus, Arsenicum album appears to have great potential for ameliorating arsenic induced elevated ANA titer and other hematological toxicities. PMID:16550230

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



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


Mercury exposure, malaria, and serum antinuclear/antinucleolar antibodies in amazon populations in Brazil: a cross-sectional study  

PubMed Central

Background Mercury is an immunotoxic metal that induces autoimmune disease in rodents. Highly susceptible mouse strains such as SJL/N, A.SW, B10.S (H-2s) develop multiple autoimmune manifestations after exposure to inorganic mercury, including lymphoproliferation, elevated levels of autoantibodies, overproduction of IgG and IgE, and circulating immune complexes in kidney and vasculature. A few studies have examined relationships between mercury exposures and adverse immunological reactions in humans, but there is little evidence of mercury-associated autoimmunity in humans. Methods To test the immunotoxic effects of mercury in humans, we studied communities in Amazonian Brazil with well-characterized exposures to mercury. Information was collected on diet, mercury exposures, demographic data, and medical history. Antinuclear and antinucleolar autoantibodies (ANA and ANoA) were measured by indirect immunofluorescence. Anti-fibrillarin autoantibodies (AFA) were measured by immunoblotting. Results In a gold mining site, there was a high prevalence of ANA and ANoA: 40.8% with detectable ANoA at ?1:10 serum dilution, and 54.1% with detectable ANA (of which 15% had also detectable ANoA). In a riverine town, where the population is exposed to methylmercury by fish consumption, both prevalence and levels of autoantibodies were lower: 18% with detectable ANoA and 10.7% with detectable ANA. In a reference site with lower mercury exposures, both prevalence and levels of autoantibodies were much lower: only 2.0% detectable ANoA, and only 7.1% with detectable ANA. In the gold mining population, we also examined serum for AFA in those subjects with detectable ANoA (?1:10). There was no evidence for mercury induction of this autoantibody. Conclusions This is the first study to report immunologic changes, indicative of autoimmune dysfunction in persons exposed to mercury, which may also reflect interactions with infectious disease and other factors.

Silva, Ines A; Nyland, Jennifer F; Gorman, Andrew; Perisse, Andre; Ventura, Ana Maria; Santos, Elizabeth CO; de Souza, Jose M; Burek, CL; Rose, Noel R; Silbergeld, Ellen K



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


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



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



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, we are studying the incidence of antibodies to nuclear antigens (DNA, ENA, and FANA) in patients with end stage kidney disease, in patients on chronic di...

K. D. Nolph G. C. Sharp



Anti-nuclear fantasies  

Microsoft Academic Search

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



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))



Anti-Idiotype RNA Selected with an Anti-Nuclear Export Signal Antibody is Actively Transported in Oocytes and Inhibits Rev and Cap-Dependent RNA Export  

Microsoft Academic Search

The anti-idiotype approach is based on the assumption that an antibody specific for a receptor-binding domain of a ligand could be structurally related to the receptor. Therefore, a structural mimic of a receptor-binding domain, selected with an anti-ligand antibody, might be a functional substrate for the receptor. This hypothesis was addressed here by generating antibodies recognizing the Rev-nuclear export signal

Jorg Hamm; Jochen Huber; Reinhard Luhrmann



A 35YearOld Woman with Puffy Hands, Raynaud’s Phenomenon, and Positive Antinuclear Antibody Test  

Microsoft Academic Search

\\u000a Systemic sclerosis (scleroderma) is classified based on the extent of skin involvement as either limited cutaneous or diffuse\\u000a cutaneous scleroderma. Patients with the limited cutaneous form of systemic sclerosis, once known as the CREST syndrome (Calcinosis,\\u000a Raynaud’s phenomenon, Esophageal dysmotility, Sclerodactyly, Telangiectasias), often report a long history of Raynaud’s phenomenon\\u000a preceding other clinical manifestations. Current classification criteria lack sensitivity for

Richard M. Silver


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.



Antinuclear Factor, a Dysimmunological Feature in Mental Depression. A Preliminary Communication  

Microsoft Academic Search

Antinuclear factor was present in the serum of more than one-fourth of 32 patients admitted to the psychiatric hospital because of mental depression. It appears that a positive antinuclear factor may be a rather common finding in endogenous depressions and the present data suggest that the presence of this serum factor is of unfavourable prognostic significance.

R. D. Deberdt; J. van Hooren; W. Amery



D-penicillamine- and quinidine-induced antinuclear antibodies in A.SW (H-2s) mice: similarities with autoantibodies in spontaneous and heavy metal-induced autoimmunity.  


Ten percent of human lupus syndromes occur in patients as a result of treatment with certain medications. H-2s mice can produce autoantibodies following treatment with various drugs or heavy metals and they are a potential animal model of drug-induced lupus. We have examined nine anti-chromatin monoclonal antibodies (mAb) from A.SW mice that had been treated with either D-penicillamine or quinidine, two lupus-inducing drugs in humans. These mAb are specific either for DNA or histone-DNA complexes corresponding to nucleo-specific either for DNA or histone-DNA complexes corresponding to nucleosomes or subnucleosome particles. Only one mAb reacts with an unknown chromatin antigen. The V region sequences of six of these mAb were studied and are notable by several features. As previously observed in spontaneous autoantibodies to DNA or histone-DNA complexes, arginine or asparagine residues are found at critical locations throughout the V regions. Many of these residues, potentially important for binding to DNA or DNA-histone complexes, result either from somatic mutations or atypical VH-D-JH rearrangements. Another significant characteristic is that the VH genes of several D-penicillamine- or quinidine-induced mAb are most similar to those of anti-nucleolar mAb obtained from mercury-injected A.SW mice. The implications of these findings for the pathogenesis of spontaneous or induced autoimmunity are discussed. PMID:8125139

Monestier, M; Novick, K E; Losman, M J



High-titer antineutrophil cytoplasmic antibodies in type-1 autoimmune hepatitis  

Microsoft Academic Search

Background\\/Aims:Autoimmune hepatitis (AIH), an unresolving liver inflammation characterized by periportal hepatitis and presence of serum autoantibodies, is distinguished by smooth muscle antibody and\\/or antinuclear antibody seropositivity. Type-2 AIH is characterized by antibodies to liver\\/kidney microsome type-1. Antineutrophil cytoplasmic antibodies (ANCAs) are highly specific for ulcerative colitis, primary sclerosing cholangitis, and, in this report, type-1 AIH determined by positive enzyme-linked immunosorbent

Stephan R. Targan; Carol Landers; Alda Vidrich; Albert J. Czaja



False-positive human immunodeficiency virus antibody test and autoimmune hemolytic anemia in a patient with angioimmunoblastic T-cell lymphoma.  


A 44-year-old woman was admitted with generalized lymphadenopathy, which was diagnosed as angioimmunoblastic T-cell lymphoma (AITL). The patient showed autoimmune hemolytic anemia (AIHA), polyclonal hypergammaglobulinemia and a high antinuclear antibody titer. Moreover, a human immunodeficiency virus (HIV)-1/2 screening test using the particle agglutination method was reactive. After chemotherapy for AITL, the AIHA was eliminated, and the false-positive HIV results were no longer detected. Autoimmunity associated with AITL is the likely cause of the cross-reaction with HIV and the AIHA. It is important to recognize that the cross-reaction with HIV can be a potential complication in AITL as well as AIHA. PMID:22001471

Shida, Seiji; Takahashi, Naoto; Fujishima, Naohito; Kameoka, Yoshihiro; Nara, Miho; Fujishima, Masumi; Saitoh, Hirobumi; Tagawa, Hiroyuki; Hirokawa, Makoto; Ichinohasama, Ryo; Sawada, Kenichi



Philosophic roots of Western antinuclear movements  

Microsoft Academic Search

The popular campaign in the West against nuclear weapons (also called the antinuclear movement or the peace movement) has been waged for over 30 years. Although one can debate its impact and influence, one cannot doubt its staying power. The antinuclear movement may rise--as it did in the late 1950's and late 1970s--and fall--as it did in the mid-1960s and




Optimized detection of circulating anti-nuclear envelope autoantibodies by immunofluorescence  

Microsoft Academic Search

BACKGROUND: Antinuclear antibodies are useful diagnostic tools in several autoimmune diseases. However, the routine detection of nuclear envelope autoantibodies using immunofluorescence (IF) is not always easy to perform in patients' sera because of the presence of autoantibodies to other nuclear and cytoplasmic components which could mask the characteristic rim-like pattern of nuclear envelope autoantibodies. This is particularly common in sera

Vagia Tsiakalou; Elena Tsangaridou; Hara Polioudaki; Artemissia-Phoebe Nifli; Meri Koulentaki; Tonia Akoumianaki; Elias Kouroumalis; Elias Castanas; Panayiotis A Theodoropoulos



Treatment with interferon-? does not induce anti-nuclear and anti-neuronal serum autoantibodies in multiple sclerosis patients.  


Type I interferons (IFNs) are known to enhance humoral immunity. Here, we investigated the prevalence and titer of anti-nuclear and anti-neuronal IgG autoantibodies in 71 relapsing-remitting MS patients classified based on their clinical response to IFN? in paired sera obtained at baseline and after 12months of treatment. All samples were negative for antibodies against cytoplasmic rods/rings, synaptic proteins and paraneoplastic antibodies. Regarding anti-nuclear, anti-filament and anti-myelin antibodies, pre- and post-treatment prevalence and titers did not differ significantly between IFN? responders and non-responders. Thus, pattern of anti-nuclear and anti-neuronal autoantibodies does not predict the response to IFN? in MS patients. PMID:23182615

Comabella, M; Rentzsch, K; Río, J; Bustamante, M F; Borowski, K; Stoecker, W; Montalban, X



False-positive results in ELISA-based anti FVIII antibody assay may occur with lupus anticoagulant and phospholipid antibodies.  


The evaluation of a prolonged aPTT often includes Lupus Anticoagulant, Antiphospholipid Antibodies, and Factor VIII (FVIII) inhibitors. We have noticed that patient samples positive for lupus antibody (LA) are frequently also positive for FVIII IgG antibodies in an enzyme-linked immunosorbent assay (ELISA), indicating the need for follow-up testing with a more labour-intensive functional assay for FVIII inhibition. This study evaluates the potential for a FVIII IgG ELISA to yield false-positive results in patient samples positive for LA or other antiphospholipid antibodies. A total of 289 residual de-identified patient samples positive for LA (n = 143), anti-cardiolipin IgG (n = 84), or beta2-glycoprotein antibody (n = 62) were tested for FVIII IgG using a commercial ELISA. Samples with positive FVIII IgG ELISA results were further tested for FVIII activity using a clot-based FVIII inhibitor assay. The FVIII IgG ELISA yielded positive results in 39 (13%) of the samples tested, including 13/143 (13%) LA-positive, 15/85 (18%) aCL IgG-positive and 6/62 (10%) ?2-glycoprotein IgG-positive samples. The clot-based FVIII inhibitor assay yielded negative results in all 39 FVIII IgG-positive specimens tested, indicating discrepancy with the FVIII IgG ELISA results. Patient specimens positive for LA, aCL IgG, or ?2-glycoprotein IgG may yield false-positive results for FVIII antibodies. Caution is warranted in interpreting FVIII antibody results in these cases. PMID:22458845

Sahud, M; Zhukov, O; Mo, K; Popov, J; Dlott, J



Implications of thyroglobulin antibody positivity in patients with differentiated thyroid cancer: a clinical position statement.  


Background: Even though the presence of antithyroglobulin antibodies (TgAbs) represents a significant problem in the follow-up of patients with differentiated thyroid cancer (DTC), the current guidelines on the management of DTC that have been published in recent years contain no text concerning the methods to be used for detecting such antibody-related interference in thyroglobulin (Tg) measurement or how to manage TgAb-positive patients in whom Tg cannot be used reliably as a tumor marker. Aim: An international group of experts from the European Thyroid Association Cancer Research Network who are involved in the care of DTC patients met twice to form a consensus opinion on how to proceed with treatment and follow-up in TgAb-positive DTC patients based on the available evidence in the literature. Here we will report on the consensus opinions that were reached regarding technical and clinical issues. Results: This clinical opinion article provides an overview of the available evidence and the resulting consensus recommendations. The current literature does not provide sufficient data for giving evidence-based answers to many questions arising in the care of TgAb-positive DTC patients. Where insufficient evidence was available, a thorough discussion by a group of physician-scientists, all of whom have a distinguished track record in thyroid cancer care, was held to arrive at a consensus expert opinion. The questions and answers discussed were then summarized into an algorithm for the management of TgAb-positive patients. Conclusion: We were able to define 26 consensus expert recommendations and a resulting algorithm for the care of TgAb-positive DTC patients. PMID:23692026

Verburg, Frederik A; Luster, Markus; Cupini, Cristina; Chiovato, Luca; Duntas, Leonidas; Elisei, Rossella; Feldt-Rasmussen, Ulla; Rimmele, Harald; Seregni, Ettore; Smit, Johannes W A; Theimer, Christian; Giovanella, Luca



OraQuick Rapid HIV-1 Antibody Test  

Center for Biologics Evaluation and Research (CBER)

Text Version... Anti-nuclear antibody (ANA) ... In the course of this study, two specimens were confirmed to have antibodies to HIV-1 and were ... HIV-1 Antibody Test. ... More results from


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



Fulminant hepatitis B in an infant born to a hepatitis Be antibody positive, DNA negative carrier  

Microsoft Academic Search

A boy was born to a mother who was a chronic hepatitis B virus (HBV) carrier. She was hepatitis Be (HBe) antibody positive and HBe antigen and HBV-DNA negative. The boy had not received hepatitis B vaccine and died from fulminant hepatitis at 3 months of age. This case demonstrates the need to vaccinate babies of HBe antibody positive, HBe

J Vanclaire; C Cornu; E M Sokal



The antibodies cyclic citrullinated peptides (anti-CCP) positivity could be a promising marker in brucellosis patients presented with peripheric arthritis.  


INTRODUCTION: The anti-cyclic citrullinated peptide (anti-CCP) enzyme-linked immunosorbent assay has a high sensitivity and specificity for rheumatoid arthritis (RA). It has been used in especially early diagnosis of RA, and used to discriminate from other forms of arthritis. Anti-CCP positivity is unknown in brucellosis presented with peripheric arthritis (BPA), like other rheumatic diseases. The objective of this study was to investigate the positivity of anti-CCP in patients with BPA in contrast to the patients with RA and healthy controls. Additionally, we have aimed to monitor changes of anti-CCP levels following the brucellosis treatment. METHODS: The study group consisted of 137 subjects. 62 brucellosis patients presented with peripheric arthritis. Additionally, 33 RA patients and 42 healthy subjects selected as control groups. The anti-CCP, rheumatoid factor and anti-nuclear antibody levels of the subjects were measured. RESULTS: Concerning the 62 BPA, 20 % (13 patients) of them had elevated anti-CCP levels. On the other side, of the 33 RA patients, 78.78 % (26 patients) of them had increased anti-CCP levels. Only one healthy subject's anti-CCP level was positive. There was statistically significant difference among the groups. After brucellosis treatment, monitorisation of the 13 patients with BPA who have the positive anti-CCP levels, were challengingly interesting because none of the patients had positive anti-CCP levels. CONCLUSIONS: Anti-CCP may be positive marker in the diagnosis of BPA but clinicians need to be careful during the follow up period because it may turn into normal ranges. Additionally, patients presented with peripheric arthritis and anti-CCP positivity need to be evaluated also for the differential diagnosis of BPA. PMID:23483338

Gokhan, Azize; Turkeyler, Ibrahim Halil; Babacan, Taner; Pehlivan, Yavuz; Dag, Muhammet Said; Bosnak, Vuslat Kecik; Namiduru, Mustafa; Kisacik, Bunyamin; Onat, Ahmet Mesut



Antikinetochore and antitopoisomerase I antibodies in systemic scleroderma: comparative study using immunoblotted recombinant antigens, immunofluorescence, and double immunodiffusion  

Microsoft Academic Search

In 135 patients with systemic scleroderma, we compared three different methods to determine antinuclear autoantibody (ANA) specificity: indirect immunofluorescence, double immunodiffusion, and, employing recombinant antigens, immunoblotting using both marker autoantigens of this disease. A characteristic Scl-70 antibody pattern was found on HEp-2 cells in 83.8% of the patients, double immunodiffusion was positive for the Scl-70 antibodies in 81.9%, and immunoblot

M. Jarzabek-Chorzelska; M. Blaszczyk; Z. Kolacinska-Strasz; T. Chorzelski; S. Jablofiska; G. G. Maul



Heterophilic antibodies interfering with radioimmunoassay. A false-positive pregnancy test  

SciTech Connect

A young woman with amenorrhea had a consistently positive pregnancy test result (serum radioimmunoassay measurement of ..beta..-human chorionic gonadotropin hormone). No fetal or placental tissue was found after uterine curettage and exploratory laparotomy. The false-positive pregnancy test result was due to heterophilic antibovine and antigoat antibodies in the patient's serum. These antibodies interfered with radioimmunoassays using goat antibodies. This case shows that serum heterophilic antibodies can interfere with immunoassays and result in unnecessary diagnostic procedures and/or unnecessary treatment.

Vladutiu, A.O.; Sulewski, J.M.; Pudlak, K.A.; Stull, C.G.



Two Unique Cases with Anti-GluR Antibody-Positive Encephalitis  

PubMed Central

We report two cases of anti-glutamic acid receptor (anti-GluR) antibody-positive encephalitis in males with symptoms such as Parkinsonism, urinary retention, and paralytic ileus. Although non-herpetic encephalitis typically shows magnetic resonance imaging (MRI) lesions in the limbic system during early stages, the present cases showed MRI lesions during later stages in the bilateral claustrum and pons. In both cases, anti-GluR?2 and ?2 antibodies were later shown to be positive in the cerebrospinal fluid but negative in the serum. Although early detection of anti-GluR antibodies is essential, early treatment may be significantly more important.

Matsuzono, Kosuke; Kurata, Tomoko; Deguchi, Shoko; Yamashita, Toru; Deguchi, Kentaro; Ikeda, Yoshio; Abe, Koji



Antimitochondrial antibody negative primary biliary cirrhosis: a distinct syndrome of autoimmune cholangitis.  

PubMed Central

This study reports on a group of 20 patients with an initial diagnosis of primary biliary cirrhosis (PBC) whose serum tested negative for antimitochondrial antibodies by immunofluorescence. All had a clinical history compatible with primary biliary cirrhosis, and results of biochemical, histological, and radiological investigations were consistent with this diagnosis despite the absence of antimitochondrial antibodies by immunofluorescence. For comparison, these patients were matched for sex and serum bilirubin with 20 antimitochondrial antibody positive (> 1:160) and histologically confirmed primary biliary cirrhosis patients who served as controls. Serum samples from both groups were retested blindly for antimitochondrial antibodies using immunoblotting and for antibodies to the major M2 mitochondrial autoantigens by enzyme linked immunosorbent assay (ELISA). Three antimitochondrial antibody immunofluorescence negative patients had antimitochondrial antibodies by immunoblotting and ELISA; the remaining 17 patients were confirmed negative by all methods. The antimitochondrial antibody immunofluorescence positive controls were verified by immunoblotting or ELISA, or both. All 17 patients negative for antimitochondrial antibodies had antinuclear antibodies, often in high titres, compared with 3/17 of the antimitochondrial antibody positive controls (p = 0.0001). Additionally, the antimitochondrial antibody negative group also had significantly higher smooth muscle antibody titres (p = 0.03) and lower serum IgM (p = 0.01) and aspartate aminotransferase (p = 0.03) activities than the antimitochondrial antibody positive controls. Analysis of clinical findings, histological tests, serum bilirubin, alkaline phosphatase, alanine aminotransferase, and IgG, disclosed no significant differences between the two groups. This paper describes a group of patients with the clinical and histological features of PBC but who do not fulfil the usual criteria necessary to make this diagnosis. Because they also have very high titres of antinuclear antibodies, smooth muscle antibodies, and comparatively low IgM and aspartate aminotransferase activities, we believe they are distinct from PBC and have a syndrome of autoimmune cholangitis. Images Figure 1 Figure 2 Figure 3 Figure 4

Michieletti, P; Wanless, I R; Katz, A; Scheuer, P J; Yeaman, S J; Bassendine, M F; Palmer, J M; Heathcote, E J



Human Leukemia-Associated Anti-Nuclear Reactivity  

PubMed Central

A brilliant, coarsely granular nuclear antigen was detected by anti-complement immunofluorescence in the nuclei of acute myeloid leukemia myeloblasts. Designated as LANA (leukemia-associated nuclear antigen), the reactivity differs from that of the Epstein-Barr-virus-determined nuclear antigen (EBNA) in immunological specificity and morphological appearance, although it is visualized by the same method. Serum from acute myeloid leukemia patients gave positive reactions in 73% of the cases. In acute lymphatic leukemia, chronic myeloid leukemia, chronic lymphatic leukemia, and Burkitt's lymphoma the sera were positive in 35, 14, 19, and 24%, respectively. Two of five polycythemia and two of eleven myeloma sera were also positive. Among 61 healthy controls, 58 were negative, whereas three showed a diffuse nuclear staining with a different pattern. Among 24 carcinoma patients, 18 were negative, whereas six gave a nuclear staining with a different, diffuse pattern. Sera from 20 patients who had recovered from infectious mononucleosis were all negative. In addition to the blasts of acute myeloid leukemia, a similar reactivity was seen with two Epstein-Barr virus DNA and EBNA-negative African lymphoma biopsies and in a short-lived tissue culture line derived from one of them. LANA could be a fetal or tissue-specific antigen, a virally determined antigen, or a specific form of anti-nuclear reactivity. Images

Klein, George; Steiner, Melita; Wiener, Francis; Klein, Eva



Follow-up of primary Sjogren's syndrome patients presenting positive anti-cyclic citrullinated peptides antibody.  


Anti-cyclic citrullinated peptide antibody (anti-CCP antibody) is very useful for the diagnosis of rheumatoid arthritis (RA) and is associated with articular erosions. The specificity of anti-CCP antibody in the diagnosis of RA has been reported to be about 95 %. Because of its higher specificity in RA, we assessed the clinical features of primary Sjogren's syndrome (pSS) who were positive for anti-CCP antibody. We assessed the clinical features of 405 pSS patients. After 60 (range 7-98) months, 23 (5.6 %) patients previously diagnosed with pSS had progressed to RA. Comparing the anti-CCP positive group with the negative group, laboratory test results for anti-CCP titer and rheumatoid factor positivity with respect to clinical outcome and progression to RA, arthralgia and arthritis were significantly different. Multivariate regression analysis also showed that anti-CCP antibody titer was independently associated with progression to RA. The odds ratio of anti-CCP positivity in terms of progression to RA was 2.5 (95 % CI 1.7-3.7). Testing for anti-CCP antibody in pSS patients with arthritis may allow for the prediction of progression to RA. PMID:23179261

Ryu, Yang-Seon; Park, Sung-Hwan; Lee, Jennifer; Kwok, Seung-Ki; Ju, Ji-Hyeon; Kim, Ho-Youn; Jeon, Chan-Hong



Methods for detection and characterization of anti-nuclear antibodies  

Microsoft Academic Search

Conclusion The detection and characterization of ANA can actually be done in most clinical laboratories using commercially available ready-to-use reagents. However when chosing a kit great care should be taken in the selection of standardized preparations previously tested with a large reference panel of sera, including a maximum of ANA patterns as well as negative control sera, to be sure

R. L. Humbel



False positive antineutrophil cytoplasmic antibody in a patient with infective endocarditis  

Microsoft Academic Search

We report a gentleman suffering from purpuric skin rash mimicking vasculitis associated with impaired renal function. He was found to have positive cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCA) in the serum, but the test for anti-proteinase 3 antibodies (PR3-ANCA) was negative. Blood culture and echocardiogram confirmed the diagnosis of Streptococcal Oralis infective endocarditis. The renal biopsy did not show any features

Chi-Yuen CHEUNG; Kim-Ming WONG; Yiu-Han CHAN; Wai-Leung CHAK; Koon-Shing CHOI; Siu-Kwong CHAN; Ka-Foon CHAU; Chun-Sang LI



Cell, tissue-, and position-specific monoclonal antibodies against the planarian Dugesia (Girardia) tigrina  

Microsoft Academic Search

To obtain specific immunological probes for studying molecular mechanisms involved in cell renewal, cell differentiation,\\u000a and pattern formation in intact and regenerating planarians, we have produced a hybridoma library specific for the asexual\\u000a race of the freshwater planarian Dugesia (Girardia) tigrina. Among the 276 monoclonal antibodies showing tissue-, cell-, cell subtype-, subcellular- and position-specific staining,\\u000a we have found monoclonal antibodies

D. Bueno; Jaume Baguñà; Rafael Romero



Clinicoimmunopathologic findings in Atlantic bottlenose dolphins Tursiops truncatus with positive cetacean morbillivirus antibody titers.  


Sera from free-ranging Atlantic bottlenose dolphins Tursiops truncatus inhabiting the Indian River Lagoon (IRL), Florida were tested for antibodies to cetacean morbilliviruses from 2003 to 2007 as part of a multidisciplinary study of individual and population health. A suite of clinicoimmunopathologic variables were evaluated in morbillivirus-seropositive dolphins (n = 14) and seronegative healthy dolphins (n = 49). Several important differences were found. Serum alkaline phosphatase, creatine phosphokinase, chloride, albumin and albumin/globulin ratios were significantly lower in seropositive dolphins. Innate immunity appeared to be upregulated with significant increases in lysozyme concentration and marginally significant increases in monocytic phagocytosis. Adaptive immunity was also impacted in dolphins with positive morbillivirus antibody titers. Mitogen-induced T lymphocyte proliferation responses were significantly reduced in dolphins with positive morbillivirus antibody titers, and marginally significant decreases were found for absolute numbers of CD4+ lymphocytes. The findings suggest impairment of cell-mediated adaptive immunity, similar to the immunologic pattern reported with acute morbillivirus infection in other species. In contrast, dolphins with positive morbillivirus antibody titers appeared to have at least a partially upregulated humoral immune response with significantly higher levels of gamma globulins than healthy dolphins, which may represent an antibody response to morbillivirus infection or other pathogens. These data suggest that subclinical dolphin morbillivirus infection in IRL dolphins may produce clinicoimmunopathologic perturbations that impact overall health. PMID:22303627

Bossart, Gregory D; Romano, Tracy A; Peden-Adams, Margie M; Schaefer, Adam; McCulloch, Stephen; Goldstein, Juli D; Rice, Charles D; Saliki, Jeremiah T; Fair, Patricia A; Reif, John S



Seroprevalence of parvovirus B19 antibody in HIV positive asymptomatic persons  

Microsoft Academic Search

Objective: Parvovirus B19 is an important cause of chronic anemia in human immunodeficiency virus (HIV)-positive patients. Extensive seroprevalence studies for parvovirus B19 in HIV-positive individuals have not been carried out in the United States. The authors compared the seroprevalence for parvovirus B19 among patients with asymptomatic HIV infection and healthy blood donors.Methods: The seroprevalence of IgG antibodies to VP-1, a

David H. Dockrell; Gregory A. Poland; Thomas E. Smith; Mary E. Jones; Peter C. Wollan; Scott R. Strickland; Claire Pomeroy



The influence of anti-cyclic citrullinated peptide on anticentromere antibody-positive rheumatoid arthritis patients  

Microsoft Academic Search

We read with interest the paper of Bournia and colleagues that anticentromere antibody (ACA)-positive primary Sjögren’s syndrome (SS) shows a clinical phenotype intermediate between ACA-negative SS and systemic sclerosis (SSc) [1]. In our past study investigating the clinical features of 62 patients with positive ACA, only one patient had typical CREST syndrome, 9 patients had Raynaud’s phenomenon (8 with sclerodactyly,

La-He Jearn; Think-You Kim



Identification and Repair of Positive Binding Antibodies Containing Randomly Generated Amber Codons from Synthetic Phage Display Libraries  

Microsoft Academic Search

Phage display technology allows for the rapid isolation and characterization of monoclonal antibodies that have vast potential for therapeutic and diagnostic applications. However, the panning process, which utilizes a host strain that suppresses termination by the amber codon, has an inherent bias toward clones containing randomly generated amber stop codons, complicating identification of positive binding antibodies when the antibody genes

Warren D. Marcus; Stuart M. Lindsay; Michael R. Sierks



No effect of immunomodulatory therapy in focal epilepsy with positive glutamate receptor type 3--antibodies.  


Antibodies against the glutamate receptor type 3-(GluR3) have been found in association with Rasmussen's encephalitis (RE) but were also detected in patients with non-inflammatory focal epilepsies. We report the case of an 18-year-old patient with treatment refractory left mesial temporal lobe epilepsy accompanied by high levels of GluR3 antibodies. Different from experiences in patients with RE immunomodulatory therapy by use of intravenous gammaglobulines neither altered GluR3 serum levels nor had any effect on seizure frequency in our patient. Interestingly, GluR3 serum levels remained positive after successful surgical intervention leading to patient's seizure freedom. PMID:16621617

Feichtinger, Michael; Wiendl, Heinz; Körner, Eva; Holl, Alexander; Gruber, Lucia; Fazekas, Franz; Schröttner, Oskar; Eder, Hans; Ott, Erwin



Primary Thrombosis Prophylaxis in Antiphospholipid Antibody–Positive Patients: Where Do We Stand?  

Microsoft Academic Search

Persistently positive antiphospholipid antibodies (aPLs) with thrombosis and\\/or pregnancy morbidity are the hallmark of the\\u000a antiphospholipid syndrome. However, aPL-positive patients with no prior history of thrombosis exist. On the basis of a limited\\u000a number of studies that predominantly included systemic lupus erythematosus patients, aPL-positive patients without previous\\u000a thrombosis have a 0% to 3.8% annual incident thrombosis risk. Given that every

Medha Barbhaiya; Doruk Erkan



[Clinical consequence and significance of anti-neutrophil cytoplasmic antibody positivity in anti-glomerular basement membrane disease].  


Introduction: Patients with renopulmonary syndrome who have both anti-neutrophil cytoplasmic and anti-glomerular basement membrane antibodies have been described since 1989. Aim: The aim of the authors was to analyse the data of "double positive" patients diagnosed in their department, and compare these with previous studies. Method: During the last 16 years, 87 anti-neutrophil cytoplasmic antibody positive and 11 anti-glomerular basement membrane antobody positive patients were diagnosed. Four patients with anti-glomerular basement membrane antibodies (36%) had detectable anti-neutrophil cytoplasmic antibodies, 2 patients were positive for anti-myeloperoxidase and 2 patients for anti-proteinase 3. Results: In comparison with patients having anti-glomerular basement membrane antibodies, the double-positive patients were characterized by older age (median of 46 vs. 24 years), lack of male dominance (50% vs. 71%), more frequent presence of previous extrarenal symptoms (50% vs. 0%), and lower anti-glomerular basement membrane antibody levels (<100EU/ml: 100% vs. 29%). The double-positive patients had more favourable 1-year survival (100% vs. 71%), despite their older age and similar treatment regimen (immunosuppression 100% in both groups, plasmapheresis in 75% vs. 86%), but 1-year renal survival was not different (25% vs. 14%). Conclusions: In agreement with literature data, about one third of patients with anti-glomerular basement membrane antibodies had detectable anti-neutrophil cytoplasmic antibodies, and the coexistence of the two antibodies may have clinical consequences. Orv. Hetil., 154 (43), 1696-1701. PMID:24140508

File, Ibolya; Pucsok, Klára; Trinn, Csilla; Ujhelyi, László; Balla, József; Mátyus, János



Anticentromere-protein-B-DNA complex activities in anticentromere antibody-positive patients  

Microsoft Academic Search

Centromere protein B (CENP-B), which is an alphoid DNA binding protein, is the target antigen in autoimmune disease patients (often those with scleroderma). In this study, we analysed activities of anti-CENP-B-DNA complex in anticentromere antibody (ACA)-positive patients using DNA immunoprecipitation with purified CENP-B. The activities correlated with ACA titres and were closely associated with Raynaud's phenomenon. Patients with CREST symptoms

Y. Muro; Y. Matsumoto; M. Ohashi



Political returns: irony, theory, and the antinuclear movement  

Microsoft Academic Search

This dissertation explores the theoretical relationship between the concept of irony and the concept of politics, and culminates in an argument regarding the presence of irony within the politics of the anti-nuclear movement. The work begins with a discussion of certain contemporary accounts of the concept of politics in ancient Greece, and a critique of a literal notion of political





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.

Darryl Leja (National Human Genome Research Institute REV)



How to manage patients with systemic lupus erythematosus who are also antiphospholipid antibody positive.  


Between 20% and 40% of patients with systemic lupus erythematosus (SLE) have positive blood tests for antiphospholipid antibodies (aPLs). This article explains what tests are used to detect these antibodies and outlines the complexities of interpreting and acting upon a positive result. If aPLs are persistently positive, the patient may develop antiphospholipid syndrome (APS) characterised by vascular thrombosis, pregnancy morbidity or both. In patients with SLE who are aPL-positive but have not developed APS, there is some evidence that low-dose aspirin should be used prophylactically, but it is not conclusive. APS in patients with SLE is clinically similar to primary APS and should be treated in the same way, with anticoagulation to prevent recurrent thrombosis or with aspirin and sometimes heparin to prevent pregnancy loss. Current best practice in use of these treatments is discussed. However, these treatments are not ideal as they can have major side effects such as haemorrhage. Research which may lead to better, more targeted therapy for APS is discussed at the end of the article. PMID:19591782

Giles, Ian; Rahman, Anisur



Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2\\/ neu -positive tumour cells  

Microsoft Academic Search

Trastuzumab (Herceptin®), a humanized IgG1 antibody raised against the human epidermal growth factor receptor 2 (HER2\\/neu), is the main antibody in clinical use against breast cancer. Pre-clinical evidence and clinical studies indicate that trastuzumab\\u000a employs several anti-tumour mechanisms that most likely contribute to enhanced survival of patients with HER2\\/neu-positive breast carcinomas. New strategies are aimed at improving antibody-based therapeutics like

Panagiotis Karagiannis; Josef Singer; James Hunt; Samuel K. E. Gan; Sarah M. Rudman; Diana Mechtcheriakova; Regina Knittelfelder; Tracy R. Daniels; Philip S. Hobson; Andrew J. Beavil; James Spicer; Frank O. Nestle; Manuel L. Penichet; Hannah J. Gould; Erika Jensen-Jarolim; Sophia N. Karagiannis



Mesothelial cell and anti-nuclear autoantibodies associated with pleural abnormalities in an asbestos exposed population of Libby MT.  


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. PMID:22085844

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



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


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



Review of the use of hepatitis B core antibody-positive kidney donors.  


This article reviews the risks of transplanting hepatitis B core antibody (anti-HBc)-positive (+) kidneys and strategies to minimize the risks to the recipient. In the United States, there is a shortage of kidneys available for transplantation. Presently, 4% of kidneys transplanted are anti-HBc (+). In published retrospective studies, the serologic conversion rate for recipients of anti-HBc (+) kidneys varied between 0% and 27%; and the development of elevated hepatic transaminases varied between 0% and 26%. Only one published article had a trend toward increased risk of graft loss. Other published studies had no significant difference in graft or patient survival. Factors that influence the risk of transmission include hepatitis B viral load, vaccination, and antiviral therapy. If the donor is anti-HBc (+) and hepatitis B DNA negative, the risk of transmission is negligible; unfortunately, this information may not be available at the time of transplant. Vaccinated recipients with a protective hepatitis B surface antibody of at least 10 mIU/mL had a 4% conversion rate compared with 10% in recipients with antibody levels not exceeding 10 mIU/mL. Both hepatitis B immunoglobulin and lamivudine have been used in recipients of anti-HBc (+) kidneys to decrease seroconversion with success. The data do support the use of anti-HBc (+) kidneys if precautions are taken. The recipients should be informed of the risk, should be vaccinated with an adequate response, and should have surveillance serologies performed. PMID:20655722

Ouseph, Rosemary; Eng, Mary; Ravindra, Kadiyala; Brock, Guy N; Buell, Joseph F; Marvin, Michael R



Muscle-Specific Receptor Tyrosine Kinase Antibody Positive Myasthenia Gravis Current Status  

PubMed Central

Muscle-specific tyrosine-kinase-antibody-positive myasthenia gravis (MuSK-MG) has emerged as a distinct entity since 2001. This disease has been reported worldwide, but with varying rates among patients with generalized acetylcholine-receptor-antibody-negative MG. MuSK-MG was detected in approximately 37% of generalized acetylcholine receptor antibody-negative MG. MuSK-MG patients were predominantly female with more prominent facial and bulbar involvement and more frequent crises. Disease onset tended to be earlier. Patients tended to have a relatively poor edrophonium response but showed prominent decrement in the repetitive nerve stimulation test in the facial muscles. Patients were more likely to display poor tolerance of, or a lack of improvement with, anticholinesterase agents. Somewhat better response was observed with steroids and plasma exchange. Most were managed successfully with aggressive immunomodulatory therapies, although a higher proportion of MuSK-MG patients had a refractory course when compared with other forms of generalized MG. I present here an up-to-date overview on MuSK-MG based on our experience at the University of Alabama at Birmingham and the existing literature.



Surface display of a single-domain antibody library on Gram-positive bacteria.  


Combinatorial protein engineering for selection of proteins with novel functions, such as enzymes and affinity reagents, is an important tool in biotechnology, drug discovery, and other biochemical fields. Bacterial display is an emerging technology for isolation of new affinity proteins from such combinatorial libraries. Cells have certain properties that are attractive for directed evolution purposes, in particular the option to use quantitative flow-cytometric cell sorting for selection of binders. Here, an immune library of around 10(7) camelid single-domain antibody fragments (Nanobodies) was displayed on both the Gram-positive bacterium Staphylococcus carnosus and on phage. As demonstrated for the first time, the antibody repertoire was found to be well expressed on the bacterial surface and flow-cytometric sorting yielded a number of Nanobodies with subnanomolar affinity for the target protein, green fluorescent protein (GFP). Interestingly, the staphylococcal output repertoire and the binders from the phage display selection contained two slightly different sets of clones, containing both unique as well as several similar variants. All of the Nanobodies from the staphylococcal selection were also shown to enhance the fluorescence of GFP upon binding, potentially due to the fluorescence-based sorting principle. Our study highlights the impact of the chosen display technology on the variety of selected binders and thus the value of having alternative methods available, and demonstrates in addition that the staphylococcal system is suitable for generation of high-affinity antibody fragments. PMID:23064703

Fleetwood, Filippa; Devoogdt, Nick; Pellis, Mireille; Wernery, Ulrich; Muyldermans, Serge; Ståhl, Stefan; Löfblom, John



Anti-nuclear attitudes in New Zealand and Australia  

SciTech Connect

The vast South Pacific, so near to Southeast Asia and vital sea lines of communications, is of great strategic value to the United States and the West. Peace in the South Pacific has depended on regional cooperation, primarily under ANZUS-the alliance of Australia, New Zealand, and the United States. But New Zealand broke alliance ranks when it refused in early 1985 to allow a US ship to call at its ports following an ANZUS sea exercise. Coupled with the stern US response of suspending military cooperation with New Zealand, the incident threw into doubt the future of the South Pacific accord. This monograph, by Dr. Dora Alves of the National Defense University, examines the regional events leading to New Zealand's action and the resulting furor. Because the center of the incident is the issue of nuclear arms, Dr. Alves focuses on the growth of anti-nuclear attitudes in New Zealand, where the ruling Labour Party adopted an anti-nuclear stance as policy. Dr. Alves' work is both a case study of the interaction of domestic politics with international treaty obligations and a discussion of the strong anti-nuclear attitudes of many South Pacific inhabitants.

Alves, D.



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.  


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



Acute Tubulo-interstitial Nephritis with Positive Anti-Neutrophil Cytoplasmic Antibodies.  


Introduction: Anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis involving the kidney usually comprises pauci-immune, necrotizing glomerulonephritis with crescents. Mononuclear tubulo-interstitial infiltrates are common in ANCA associated vasculitis, but these have usually been described in conjunction with glomerulitis. Acute tubulo-interstitial nephritis (ATIN) is a common cause of acute kidney injury that is most frequently induced by drugs or infections. Idiopathic ATIN has rarely been reported in association with the presence of a positive ANCA. These two entities seem to share a common immunological basis. Case report: We report a 75 years-old male patient who presented with acute kidney injury and his serum tested positive for p-ANCA by indirect immunofluoresence with a titer of 1/320. Testing by ELISA demonstrated anti-myeloperoxidase (MPO) specificity with a level of 28.8 IU/mL. His kidney biopsy showed features of ATIN with no glomerular involvement. Treatment with corticosteroids led to improvement of his kidney function and serology for ANCA became negative. In this case report ATIN seems to be associated with ANCA positivity, in the absence of other obvious causes for the acute tubulo-interstitial insult. Conclusion: ATIN can be associated with positive ANCA without features of renal-limited vasculitis or systemic vasculitis. This can occur in the absence of drug exposure. The outcome in our case was favorable with corticosteroid therapy. Key words: ANCA; Acute Tubulo-interstitial Nephritis; Pathogenesis. PMID:24053745

Hassani, Kawtar; Hamzi, Amine Mohamed; Hassani, Mohamed; Benyahia, Mohamed



Positive deamidated gliadin peptide antibodies and negative tissue transglutaminase IgA antibodies in a pediatric population: to biopsy or not to biopsy.  


Reports from our clinical laboratory database show that 75% of children <2 years old tested for celiac serology who were found positive for deamidated gliadin peptide (DGP) antibodies had negative results for tissue transglutaminase IgA. DGP levels were shown to decline and disappear without a gluten-free diet. This observation questions DGP's specificity for diagnosis of celiac disease. PMID:20357057

Parizade, Miriam; Shainberg, Bracha



[Positive tests for serum anti-endomysium antibodies (AEA) and anti-jejunal antibodies (JAB) and histopathological diagnosis of celiac disease in children].  


Non-invasive examination methods are increasingly important in diagnosing celiac disease. New options for diagnosing celiac disease have been discovered in addition to the established biochemical, hematological and other methods as a result expansive progress ofclinical genetics and immunology. At the same time, detection of circulating auto-antibodies is becoming ever more frequent in clinical practice. As a result, many new, clinically highly heterogeneous cases of the disease have been diagnosed and consequently the prevalence of the disease in both child and adult population has grown. Detection of anti-endomysial antibodies (AEA), characteristic for their high sensitivity and specificity, plays an important role in diagnosing and monitoring celiac disease in pediatric practice. Nevertheless, histopathological diagnosis remains the critical tool for definitive diagnosis of the disease. The article refers to relations between the degree of positivity of AEA and JAB antibodies in the IgA class and the respective grade in the Marsh grading system. The objective of the study was to examine AEA and JAB antibodies and the histological picture of the duodenal mucosa in 20 children and adolescents with celiac disease aged from 2 to 18 years. The authors developed a semiquantitative scale of positivity of both the antibodies, which they compared trying to find a correlation between these and the histopathological picture of the duodenal mucosa. The authors point out the need of timely determination of AEA and t-TG (tissue transglutaminase) in patients whose anamnesis, clinical picture or laboratory results may be indicative of celiac disease. PMID:18390114

Makovický, P E; Makovický, P A; Klimik, M; Gregus, M; Zimmermann, M



EBV-positive human sera contain antibodies against the EBV BMRF-2 protein  

PubMed Central

We previously showed that the EBV glycoprotein BMRF-2 contains a functional integrin-binding Arg–Gly–Asp (RGD) domain that plays an important role in viral infection and cell-to-cell spread of progeny virions in oral epithelial cells. In this study, we found that EBV-seropositive human sera contain antibodies against BMRF-2. The inhibitory effect of EBV-positive sera on EBV infection of oral epithelial cells was substantially reduced by pre-incubation of serum samples with the BMRF-2 RGD peptide, suggesting that anti-BMRF-2 human antibodies possess neutralizing activity. EBV-specific sera reacted strongly with the BMRF-2 extracellular domain (170-213 aa) containing the RGD motif, whereas they reacted only weakly or not at all with a mutated form of the BMRF-2 extracellular domain containing AAA instead of RGD. These data indicate that that RGD motif of BMRF-2 is part of an immunodominant antigenic determinant within the extracellular domain of BMRF-2 that may contribute to EBV neutralization during EBV reactivation.

Xiao, Jianqiao; Palefsky, Joel M.; Herrera, Rossana; Sunshine, Carl; Tugizov, Sharof M.



Dual anca positivity in a child with moyamoya-like cerebral vascular changes: an unusual presentation with sudden homonymous hemianopsia.  


A 12-year-old girl presented with a sudden decrease in her right visual acuity and homonymous hemianopsia. An angiography of the retinal arteries demonstrated recanalized occlusion of the right retinal artery. Cerebral angiography showed bilateral internal carotid artery stenosis associated with the development of collateral circulation. Laboratory evaluations revealed dual antineutrophil cytoplasmic antibodies (ANCA) positivity [anti-proteinase (anti-PR3) ANCA and anti-myeloperoxidase (anti-MPO) ANCA], anticardiolipin (aCL) antibodies, and low titers of antinuclear antibodies (ANA). There was no evidence of active systemic lupus erythematosus (SLE), ANCA-related vasculitis, or other risk factors for cerebral occlusion, such as antiphospholipid syndrome (APS). Dual positivity for both cytoplasmic (c-ANCA) and perinuclear (p-ANCA) antineutrophil antibodies has been found previously in a small number of reports, but to our knowledge, this case represents the first case of moyamoya disease associated with dual ANCA positivity. PMID:21863249

Sakalli, Hale; Baskin, Esra; Alehan, Füsun; Ag?ldere, Muhte?em; Akova, Yonca Aydin; Caner, Hakan



Human immunodeficiency virus antibody screening in patients on renal replacement therapy: prevalence of false-positive results.  


Patients with terminal renal failure quite frequently receive blood transfusions on renal replacement therapy; therefore they are at increased risk of infection with human immunodeficiency virus (HIV). We investigated sera from 380 patients on haemodialysis or with a renal transplant for anti-HIV, using commercially available enzyme immunoassays (EIA). Persistent EIA-positive sera were additionally examined by Western blot and ELAVIA test, a commercially available indirect EIA. We found 20 patients (5.3%) with a persistently positive EIA screening test. None gave a positive result with confirmatory tests. Cross-reacting leucocyte antibodies seemed to be responsible for most of these false-positive anti-HIV tests; 12 of 20 EIA-positive sera were found positive for HLA antibodies. Sera from patients on haemodialysis or with a renal transplant, particularly when multiply transfused, have to be investigated carefully before infection with HIV is confirmed. PMID:3118266

Fassbinder, W; Fürsch, A; Kühnl, P; Schoeppe, W



A subset of ulcerative colitis with positive proteinase-3 antineutrophil cytoplasmic antibody  

PubMed Central

A small subset of patients with active ulcerative colitis is non-responsive to major known non-biological therapies. We reported 5 patients with positive serum proteinase-3 antineutrophil cytoplasmic antibody (PR3-ANCA) and tried to (1) identify the common clinical features of these patients; (2) investigate the efficacy of a novel therapy using a Chinese medicine compound; and (3) attract more gastroenterologists to be engaged in further study of this subset of patients. The common manifestations of disease in these 5 patients included recurrent bloody diarrhea and inflammatory lesions involving the entire colorectal mucosa. Initial treatment with intravenous methylprednisolone successfully induced remission. Four of these 5 patients were steroid-dependence, and immunosuppressants, such as azathioprine and cyclophosphamide, were ineffective. In 3 patients, only the particular Chinese medicine compound could induce and maintain remission. One patient underwent colectomy. No vascular inflammatory lesions were found by histopathological examination. Although more cases are needed for confirmation, our study indicates that ulcerative colitis with positive PR3-ANCA may belong to a subtype of refractory ulcerative colitis. The particular Chinese medicine compound used in our study is by far the most effective in the management of these patients, with additional advantages of having no noticeable side-effects and less financial burden.

Xu, Jin; Yang, Chuan-Hua; Chen, Xiao-Yu; Li, Xu-Hang; Dai, Min; Xiao, Shu-Dong



Confirmation of positive results for chlamydial antigen by the Chlamydiazyme assay: value of repeated testing and a blocking antibody assay.  

PubMed Central

We studied the specificity of the Abbott Chlamydiazyme test for detection of Chlamydia trachomatis antigen by means of a specific blocking antibody test. A total of 457 previously positive specimens were tested; 22 did not block in the blocking antibody test, 39 did not repeat as positive, and 396 were confirmed as positive. The distribution of A492 values obtained with specimens which did not repeat as positive was nonrandom and was concentrated between the cutoff values and 0.400. The positive predictive value of the Chlamydiazyme assay after initial testing was 86.7% (396 of 457), but the positive predictive value increased to 94.7% (396 of 418) if specimens which were not repeatedly positive were considered negative. We recommend routinely repeating the Chlamydiazyme assay for all specimens which give A492 values between the cutoff and 0.400 to eliminate many false-positive results. Use of the blocking antibody reagent can then be reserved for confirming only specimens which are repeatedly positive.

Olsen, M A; Sambol, A R



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


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



Political returns: irony, theory, and the antinuclear movement  

SciTech Connect

This dissertation explores the theoretical relationship between the concept of irony and the concept of politics, and culminates in an argument regarding the presence of irony within the politics of the anti-nuclear movement. The work begins with a discussion of certain contemporary accounts of the concept of politics in ancient Greece, and a critique of a literal notion of political community is proposed as an indirect introduction for the theme of political community as ironic. In the second chapter, the thesis regarding the place of irony within the Greek conception of political community is illustrated by way of an intensive reading and reinterpretation of Plato's Republic. The next chapter attempts to answer the question, What is irony.; and to that end, an argument concerning the relationship between philosophic and literary formulations of irony is forwarded. The fourth chapter examines the theorists and theories of philosophic irony in the 19th century. In the final chapter, certain theories of the strategy of nonviolent resistance are analyzed and in response it is argued that an element of political irony is implicit within the general idea of nonviolent resistance and that an ironic view of political community informs the nonviolent protest activities of the anti-nuclear movement in particular.

Seery, J.E.



Immune Modulation Therapy in a CRIM-Positive and IgG Antibody-Positive Infant with Pompe Disease Treated with Alglucosidase Alfa: A Case Report.  


Pompe disease is characterized by deficiency or absence of activity of the lysosomal enzyme acid alpha-glucosidase. As a result of ineffective metabolism, glycogen progressively accumulates in muscle tissues. Patients with an aggressive classic infantile-onset form generally rapidly die of cardiorespiratory failure. A cross-reactive immunological material (CRIM)-negative status is predictive of high anti-alglucosidase alfa antibody titers and usually a poor clinical outcome of enzyme replacement therapy (ERT). CRIM-positive patients can also develop robust antibody titers complicating therapeutic management.We successfully used an immune modulation therapy (IMT) protocol in a CRIM-positive infantile-onset patient with Pompe disease in whom infusions had to be temporarily discontinued because of safety concerns despite administration of pre-infusion medication. Prior to discontinuation, she had shown signs of clinical deterioration and continuous ventilation support through a tracheostomy was required. She was found to be positive for anti-alglucosidase alfa antibodies (1:6,400). IMT (rituximab, methotrexate and intravenous gamma globulin) was started, ERT was safely reintroduced during the IMT induction phase and, subsequently, the enzyme dose was increased, all without any complications. Antibodies disappeared, IMT was tapered and discontinued, and cadiomyopathy steadily improved. During 1 year of follow-up, she remained ventilator dependent and no gains in motor skills were noticed; motor functions will be closely monitored during sustained ERT.Although the reversal of clinical decline in our CRIM-positive and antibody-positive infant with Pompe disease cannot be solely attributed to IMT, our experiences with this protocol may be helpful to other physicians encountering comparable therapeutic dilemmas. PMID:23430847

Markic, Josko; Polic, Branka; Kuzmanic-Samija, Radenka; Marusic, Eugenija; Stricevic, Luka; Metlicic, Vitomir; Mestrovic, Julije



BP010047 / 16 - OraQuick Rapid HIV-1/2 Antibody Test ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... Collection Loops, Test Devices, and Developer Solution Vials only once and dispose of properly (see Safety Precautions ... Anti-nuclear antibody (ANA ... More results from


High rates of false-positive hepatitis C antibody tests can occur after left ventricular assist device implantation.  


Hepatitis C virus (HCV) screening is routine before cardiac transplantation, and virus presence is an exclusion at most centers. Left ventricular assist devices (LVADs) are often used as a bridge to transplantation and cause immune activation. We collected data on 32 consecutive patients undergoing LVAD placement between January 2006 and February 2008 at a single center. Of the 23 potential bridge-to-transplant patients with HCV testing before and after LVAD, seven (30%) turned positive for HCV antibody but did not have true HCV infection on confirmatory testing. Cardiac transplant care providers should be aware of possible false-positive HCV antibody tests in this setting. PMID:24088900

Srivastava, Ajay V; Hrobowski, Tara; Krese, Lori; Huang, Mary Ann; Nemeh, Hasan; Tita, Cristina; Williams, Celeste; Brewer, Robert; Lanfear, David E


Heavy chain position 50 is a determinant of affinity and specificity for the anti-digoxin antibody 26-10.  


Antibody produced by a variant of the murine antidigoxin hybridoma 26-10 has reduced affinity for digoxin but enhanced recognition of the digoxin 12-hydroxyl due to a Tyr to His substitution at heavy chain position 50 (Schildbach, J. F., Panka, D. J., Parks, D. R., Jager, G. C., Novotny, J., Herzenberg, L. A., Mudgett-Hunter, M., Bruccoleri, R. E., Haber, E., and Margolies, M. N. (1991) J. Biol. Chem. 266, 4640-4647). Consistent with these data, the 26-10 Fab-digoxin x-ray crystal structure (Jeffrey, P. D., Strong, R. K., Sieker, L. C., Chang, C. Y., Campbell, R. L., Petsko, G. A., Haber, E., Margolies, M. N., and Sheriff, S. (1993) Proc. Natl. Acad. Sci. U. S. A., in press) reveals that Tyr-50 contacts a region of digoxin that includes the hapten-12 carbon. To determine the effects of other heavy chain position 50 substitutions, mutant antibodies were engineered, and their affinities for digoxin and digoxin analogues were measured. The affinity of the mutant antibodies for digoxin roughly correlates with the size of the position 50 side chain. Substitutions of Trp or Phe have no effect on affinity, whereas substitutions of Asn, His, Leu, Ala, Gly, and Asp confer progressively lower affinities. Although Trp and Phe mutants exhibit wild-type specificity, Asn and Asp mutants have improved affinity for digoxin relative to digitoxin (12-deshydroxydigoxin). Leu, Ala, and Gly mutants have improved affinity for 12-acetyldigoxin relative to digoxin as compared with 26-10. These results indicate that position 50 is a determinant of both antibody affinity and fine specificity for antibody 26-10 and that single-amino acid substitutions can alter antibody fine specificity. Models of the mutants were computationally constructed, and haptens were docked into the modeled binding sites. The results suggest that 12-acetyldigoxigenin occupies different orientations in the 26-10 and in the Ala mutant binding sites, resulting in altered binding. PMID:7691815

Schildbach, J F; Near, R I; Bruccoleri, R E; Haber, E; Jeffrey, P D; Ng, S C; Novotny, J; Sheriff, S; Margolies, M N



The Drug User's Identity and How It Relates to Being Hepatitis C Antibody Positive: A Qualitative Study  

ERIC Educational Resources Information Center

|The increasing health problem of hepatitis C virus infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. injecting drug users). There is a lack of information about the knowledge, perceptions and feelings that injecting drug users hold about their hepatitis C antibody positive

Copeland, Lorraine



GAD Antibody Positivity Predicts Type 2 Diabetes in an Adult Population  

PubMed Central

OBJECTIVE To evaluate the significance of GAD antibodies (GADAs) and family history for type 1 diabetes (FHT1) or type 2 diabetes (FHT2) in nondiabetic subjects. RESEARCH DESIGN AND METHODS GADAs were analyzed in 4,976 nondiabetic relatives of type 2 diabetic patients or control subjects from Finland. Altogether, 289 (5.9%) were GADA+—a total of 253 GADA+ and 2,511 GADA? subjects participated in repeated oral glucose tolerance tests during a median time of 8.1 years. The risk of progression to diabetes was assessed using Cox regression analysis. RESULTS Subjects within the highest quartile of GADA+ (GADA+high) had more often first-degree FHT1 (29.2 vs. 7.9%, P < 0.00001) and GADA+ type 2 diabetic (21.3 vs. 13.7%, P = 0.002) or nondiabetic (26.4 vs. 13.3%, P = 0.010) relatives than GADA? subjects. During the follow-up, the GADA+ subjects developed diabetes significantly more often than the GADA? subjects (36/253 [14.2%] vs. 134/2,511 [5.3%], P < 0.00001). GADA+high conferred a 4.9-fold increased risk of diabetes (95% CI 2.8–8.5) compared with GADA?—seroconversion to positive during the follow-up was associated with 6.5-fold (2.8–15.2) and first-degree FHT1 with 2.2-fold (1.2–4.1) risk of diabetes. Only three subjects developed type 1 diabetes, and others had a non–insulin-dependent phenotype 1 year after diagnosis. GADA+ and GADA? subjects did not clinically differ at baseline, but they were leaner and less insulin resistant after the diagnosis of diabetes. CONCLUSIONS GADA positivity clusters in families with type 1 diabetes or latent autoimmune diabetes in adults. GADA positivity predicts diabetes independently of family history of diabetes, and this risk was further increased with high GADA concentrations.

Lundgren, Virve M.; Isomaa, Bo; Lyssenko, Valeriya; Laurila, Esa; Korhonen, Pasi; Groop, Leif C.; Tuomi, Tiinamaija



Parry-Romberg syndrome in association with anti-dsDNA antibodies: a case report.  


Parry-Romberg syndrome (PRS) is a rare and puzzling disorder that is characterized by progressive hemifacial atrophy. It involves mainly some or all tissues of one side of the face. A case of 21-year-old Caucasian man with hemifacial atrophy in the right facial region is reported. Serological studies with anti-single-stranded DNA (anti-ssDNA), anti-double-stranded DNA (anti-dsDNA), anticentromere (ACA) and antinuclear (ANA) antibodies were done. Anti-dsDNA antibodies was found positive, but the others were negative. Rheumatoid factor (RF) was also negative. Since PRS is rare and its association with anti-dsDNA antibodies was not reported before, this case appears to be the first report. PMID:16268883

Gonul, M; Dogan, B; Izci, Y; Varol, G



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

PubMed Central

Background Acute 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. Methods Volunteers 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 antigen ELISA. Five subgroups of samples were also tested by the Determine Ag/Ab Combo test 1) Antigen positive, antibody negative (acute infection); 2) Antigen positive, antibody positive; 3) Antigen negative, antibody positive; 4) Antigen negative, antibody negative; and 5) Antigen false positive, antibody negative (HIV uninfected). A sixth group included serial dilutions from a p24 antigen-positive control sample. Combo test results were reported as antigen positive, antibody positive, or both. Results Of 34 group 1 samples with VL between 5x105 and >1.5x107 copies/mL (median 3.5x106), 1 (2.9%) was detected by the Combo antigen component, 7 (20.6%) others were positive by the Combo antibody component. No group 2 samples were antigen positive by the Combo test (0/18). Sensitivity of the Combo antigen test was therefore 1.9% (1/52, 95% CI 0.0, 9.9). One false positive Combo antibody result (1/30, 3.3%) was observed in group 4. No false-positive Combo antigen results were observed. The Combo antigen test was positive in group 6 at concentrations of 80 pg/mL, faintly positive at 40 and 20 pg/mL, and negative thereafter. The p24 ELISA antigen test remained positive at 5 pg/mL. Conclusions Although the antibody component of the Combo test detected antibodies to HIV earlier than the comparison antibody tests used, less than 2% of the cases of antigen-positive HIV infection were detected by the Combo antigen component. The development of a rapid point-of-care test to diagnose acute HIV infection remains an urgent goal.

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



Environmental problems on Kazakhstan and the Nevada-Semipalatinsk antinuclear movement.  

National Technical Information Service (NTIS)

In this coherent and consistently - argued article, the authors explore ecological problems in Kazakhstan, a process of Kazakhstan's integration into international antinuclear movement. They look at what a moratorium on nuclear weapons testing Semipalatin...

K. Nesipbaeva C. Chang



Frequent chronic hepatitis B virus infection in HIV-infected patients positive for antibody to hepatitis B core antigen only  

Microsoft Academic Search

Persons with immune deficiency may present with atypical results in serological tests for hepatitis B virus (HBV). Frozen serum specimens that were sequentially obtained over time from a cohort of 57 HIV-infected patients, all of whom tested positive only for antibody to hepatitis B core antigen (anti-HBcAg), were therefore restested for HBV markers, including HBV DNA. The results were assessed

M. Hofer; H. I. Joller-Jemelka; P. J. Grob; R. Ltithy; M. Opravil



Frequent development of subclinical chronic antibody-mediated rejection within 1 year after renal transplantation with pre-transplant positive donor-specific antibodies and negative CDC crossmatches.  


Although short-term graft survival has been improved by recent desensitization protocols including B cell depletion therapy, little is known about risk factors of chronic antibody-mediated rejection (CAMR) in HLA-incompatible (HLA-I) renal transplantation (RTx). Twenty-six HLA-I RTx with positive donor-specific antibodies (DSA) and negative T cell cytotoxic crossmatches were compared with 88 ABO-incompatible (ABO-I) and 207 ABO-identical/compatible (ABO-Id/C) RTx. The desensitization therapy consisted of mycophenolate mofetil, rituximab and double-filtration plasmapheresis. Protocol biopsies within 1 year revealed subclinical CAMR in 36% of HLA-I, 5% of ABO-I and 3% of ABO-Id/C, although clinical acute AMR was observed in 8%, 3% and 1%, respectively. The incidence of CAMR was not different between class I and class II DSA. Most of class I DSA (94%) changed to negative 1 year after RTx, whereas 77% of class II DSA remained positive. In addition, the remaining DRB ± DQB DSA caused CAMR in 80% of patients, while DQB DSA alone did not. The progress of subclinical CAMR within 1 year could not be circumvented by rituximab. Sustained class II (DRB ± DQB) DSA detection after RTx may pose a potential risk for developing CAMR, but negative change in class I DSA could also elicit CAMR. PMID:23792054

Yamanaga, Shigeyoshi; Watarai, Yoshihiko; Yamamoto, Takayuki; Tsujita, Makoto; Hiramitsu, Takahisa; Nanmoku, Koji; Goto, Norihiko; Takeda, Asami; Morozumi, Kunio; Katayama, Akio; Saji, Hiroh; Uchida, Kazuharu; Kobayashi, Takaaki



The Effects of an Anti-Nuclear War Film on Attitudes toward Nuclear Issues  

Microsoft Academic Search

This study tested the effects of an anti-nuclear war film on students' attitudes toward nuclear issues. Twenty-six male and female Canadian undergraduates were shown the film “If You Love This Planet”; another 26 were shown a neutral film. Students shown the anti-nuclear war film showed more support for activism and protest against nuclear war. The study provided evidence that a

William Donald Gunn; Peter Horvath



Antiphospholipid antibodies (APA) and recurrent pregnancy loss: treating a unique APA positive population  

Microsoft Academic Search

BACKGROUND: Recurrent pregnancy loss (RPL) has been associated with antiphospholipid antibodies (APA) including anticardiolipin and lupus anticoagulant. Therapy using heparin and aspirin has been shown to significantly improve the live birth rate. We evaluated whether other APA should be considered as a basis for treatment in women with RPL. We also assessed the efficacy of heparin and aspirin therapy compared

R. D. Franklin; W. H. Kutteh



High positivity of anti-CCP antibodies in patients with Down syndrome  

Microsoft Academic Search

The aim of the present study was to evaluate the prevalence of anti-cyclic citrullinated peptide (CCP) antibodies in patients\\u000a with Down’s syndrome (DS) previously tested for IgM rheumatoid factor (RF) and to correlate the results with clinical findings.\\u000a Eighty-eight patients with DS previously tested for IgM-RF were divided into two groups matched for sex and age. Group A consists\\u000a of

Renato M. Nisihara; Thelma L. Skare; Marília B. G. Silva; Iara T. Messias-Reason; Nanci P. Oliveira; Patricia T. Fiedler; Shirley R. R. Utiyama



Science in europe/the antinuclear movement takes hold.  


Five months after the announcement of President Carter's nonproliferation policy, the common wisdom in this country is that Europe has hardly wavered in its rush toward nuclear power. The cry that "Europe will do what it wants whether the United States builds a breeder or not" is often heard from American nuclear interests, with apparent justification as the State Department has shown little visible progress in negotiating new agreements and some signs of retreating from its original goals. But popular protest against nuclear power has reached a pitch in Europe that would be barely imaginable today in this country, and the political strength of the antinuclear forces has become formidable, not only in Sweden where nuclear power was a pivotal issue last year, but across the continent. West Germany's research minister recently predicted that that country's two ruling coalition parties will vote for a complete moratorium on nuclear construction when they meet this fall, and some observers predict that any moratorium contingent on creation of a waste disposal site could last up to 12 years. Beyond public opposition, the plutonium breeder is running into trouble in Germany for many of the same reasons it has in the United States; program delays, safety concerns, and cost overruns threaten to undermine the claim that it can one day become an economically competitive energy source. Nuclear opposition is far from being a single-issue movement in Europe, as groups of many political persuasions embrace it for their own reasons. But as the following report by Nigel Hawkes details, the Carter administration policy is not the only thing holding back nuclear power in Europe.-W.D.M. PMID:17753327

Hawkes, N



Available means: manifestations of Aristotle's three modes of rhetorical appeal in antinuclear fiction  

SciTech Connect

The abundance of sympathetic scientists, military men and clergymen in antinuclear fiction reflects a public perception that authorities speak most knowledgeably about an issue. Other antinuclear works employ characters with less traditional ethical appeals: nurturing women, vital youths, and even infallible computers. Antinuclear fiction uses enthymeme and example to reflect the history of the nuclear weapons debate. Some works attach the immorality of the weapons by examining the moral dilemmas of nuclear scientists. Others admit the permanence of the nuclear threat. By arousing emotions, fiction is capable of mobilizing its audience's active support for the ideas it presents. The principal emotions that various antinuclear works arouse highlight the close relationship between literature and rhetoric. The most dominant emotions, pity and fear, are the two Aristotle links to tragedy. Scorn, the principal emotion that Dr. Strangelove arouses - is the crucial emotion on which all satire depends. However, the other principal emotion in anti-nuclear fiction - hope - has principally a rhetorical function ensuring that the feelings the works provoke will be channeled constructively.

Mannix, P.J.



Patterns of Human Papillomavirus DNA and Antibody Positivity in Young Males and Females, Suggesting a Site-Specific Natural Course of Infection  

PubMed Central

Background To monitor the impact of human papillomavirus types 16 and 18 vaccine on HPV infection dynamics in the Netherlands, we started an ongoing study in sexually transmitted infection (STI) clinics in 2009. Here, we analyze baseline type-specific HPV DNA and HPV-specific antibody positivity rates. Methods We enrolled 3569 men and women, 16–24 years of age, from 14 STI clinics, and estimated genital and anal HPV DNA and antibody positivity rates of 7 main carcinogenic HPV types. Generalized estimating equations regression analyses were applied to determine risk factors for, and associations between, type-specific HPV DNA and antibody positivity. Results Genital HPV DNA positivity rates were higher in women than in men; anal HPV DNA was especially high in men who have sex with men (MSM). HPV antibody seropositivity rates were also highest in women and MSM. High-risk sexual behavior was predictive of both HPV DNA and antibody positivity. Despite a strong correlation in serological profiles for multiple HPV types, seropositivity was independently associated with homologous HPV DNA detection. Conclusions HPV DNA and antibody positivity rates are higher in women and MSM than in heterosexual men, but their association is similar across gender. This suggests a site-specific natural course of infection.

Vriend, Henrike J.; Bogaards, Johannes A.; van der Klis, Fiona R. M.; Scherpenisse, Mirte; King, Audrey J.; van der Sande, Marianne A. B.



Congenital Heart Block Not Associated with Anti-Ro/La Antibodies: Comparison with Anti-Ro/La-positive Cases  

PubMed Central

Objective To study anti-Ro/La-negative congenital heart block (CHB). Methods Forty-five fetuses with CHB were evaluated by analysis of anti-Ro/La antibodies using sensitive laboratory methods. Results There were 9 cases of anti-Ro/La-negative CHB; 3 died (33.3%). Only 3 (33.3%) were complete in utero and 5 (55.5%) were unstable. No specific etiology was diagnosed. Six infants (66.6%) were given pacemakers. There were 36 cases of anti-Ro/La-positive CHB. All except 2 infants (94.4%) had complete atrioventricular block in utero. Ten died (27.8%), one (2.7%) developed severe dilated cardiomyopathy, and 26 (72.2%) were given pacemakers. Conclusion Nine of the 45 consecutive CHB cases (20%) were anti-Ro/La-negative with no known cause. They were less stable and complete than the anti-Ro/La positive cases.

Brucato, Antonio; Grava, Chiara; Bortolati, Maria; Ikeda, Keigo; Milanesi, Ornella; Cimaz, Rolando; Ramoni, Veronique; Vignati, Gabriele; Martinelli, Stefano; Sadou, Youcef; Borghi, Adele; Tincani, Angela; Chan, Edward K.L.; Ruffatti, Amelia



[Following sensory neuropathy, anti-Hu antibody-positive paraneoplastic neurological syndrome presenting with limbic encephalitis occurs after complete remission].  


Paraneoplastic limbic encephalitis is a rare neurological disorder that frequently precedes the detection of malignancy. We report the case of a 68-year-old male with small-cell lung cancer who developed paraneoplastic limbic encephalitis associated with presence of the anti-Hu antibody, after achieving complete remission of the tumor by chemotherapy. The patient visited our hospital because of progressive sensory disturbance of the distal extremities at 65 years of age. Though paraneoplastic sensory neuropathy was suspected, we could not find any tumor and he did not improve with steroids or immunoglobulin therapy. Chest computed tomography (CT) revealed large mediastinal lymphadenopathy. He was subsequently diagnosed with small cell lung cancer at one year and three months after the neurological symptoms occurred. As his serum analysis was positive for the anti-Hu antibody, we diagnosed paraneoplastic sensory neuropathy. The lung cancer disappeared with chemotherapy, but he had developed short-term memory loss six months later. Brain fluid attenuated inversion recovery (FLAIR) imaging showed an abnormal high-intensity lesion in the left medial temporal lobe including the hippocampus. We therefore made the diagnosis of paraneoplastic limbic encephalitis following subacute sensory neuropathy associated with the anti-Hu antibody. To our knowledge, this is the first report of a patient presenting with paraneoplastic neurological syndrome in which limbic encephalitis developed after tumor disappearance. So we must recognize the possibility of neurological symptoms occurring during remission. As the mechanism of pathogenesis, delayed neuronal cell damage due to immune responses against the tumor is implicated. PMID:23603543

Fukami, Yuki; Umemura, Toshitaka; Shimono, Tetufumi; Yokoi, Takamasa; Kamijo, Mikiko; Sakakibara, Toshimasa



A functional variant of Fc? receptor IIIA is associated with rheumatoid arthritis in individuals who are positive for anti-glucose-6-phosphate isomerase antibodies  

PubMed Central

Anti-glucose-6-phosphate isomerase (GPI) antibodies are known to be arthritogenic autoantibodies in K/B×N mice, although some groups have reported that few healthy humans retain these antibodies. The expression of Fc? receptors (Fc?Rs) is genetically regulated and has strong implications for the development of experimental arthritis. The interaction between immune complexes and Fc?Rs might therefore be involved in the pathogenesis of some arthritic conditions. To explore the relationship between functional polymorphisms in Fc?Rs (FCGR3A-158V/F and FCGR2A-131H/R) and arthritis in individuals positive for anti-GPI antibodies, we evaluated these individuals with respect to FCGR genotype. Genotyping for FCGR3A-158V/F and FCGR2A-131H/R was performed by PCR amplification of the polymorphic site, followed by site specific restriction digestion using the genome of 187 Japanese patients with rheumatoid arthritis (including 23 who were anti-GPI antibody positive) and 158 Japanese healthy individuals (including nine who were anti-GPI antibody positive). We report here on the association of FCGR3A-158V/F functional polymorphism with anti-GPI antibody positive status. Eight out of nine healthy individuals who were positive for anti-GPI antibodies possessed the homozygous, low affinity genotype FCGR3A-158F (odds ratio = 0.09, 95% confidence interval 0.01–0.89; P = 0.0199), and probably were 'protected' from arthritogenic antibodies. Moreover, among those who were homozygous for the high affinity genotype FCGR3A-158V/V, there were clear differences in anti-human and anti-rabbit GPI titres between patients with rheumatoid arthritis and healthy subjects (P = 0.0027 and P = 0.0015, respectively). Our findings provide a molecular model of the genetic regulation of autoantibody-induced arthritis by allele-specific affinity of the Fc?Rs.

Matsumoto, Isao; Zhang, Hua; Muraki, Yoshifumi; Hayashi, Taichi; Yasukochi, Takanori; Kori, Yuko; Goto, Daisuke; Ito, Satoshi; Tsutsumi, Akito; Sumida, Takayuki



Mapping the detailed specificity of a calcium-dependent monoclonal antibody through the use of soluble positional scanning combinatorial libraries: Identification of potent calcium-independent antigens  

Microsoft Academic Search

Summary The detailed specificity of monoclonal antibody M1, which has been reported to bind in a calcium-dependent manner to the ‘FLAG’ sequence DYKDDDDK-NH2, was examined using soluble hexa- and decapeptide positional scanning synthetic combinatorial libraries (PS-SCLs) made up of 52×106 and 4×1012 different sequences, respectively. To study the influence of calcium on the specificity of this antigen-antibody interaction, each PS-SCL

Clemencia Pinilla; Jaime Buencamino; Jon R. Appel; Thomas P. Hopp; Richard A. Houghten



[A case of neonatal lupus syndrome and congenital atrioventricular block associated with maternal antibodies antiRo/SS-A].  


The neonatal lupus erythematosus syndrome (LEN) is a disease due to the transplacental passage of maternal antiextractable nuclear antigens (ENA) antibodies, particularly anti-Ro/SS-A and anti-La/SS-B. The disease affects neonates born from mothers with autoimmune diseases. It is characterized by erythematous annular polycylic skin lesions, slightly scaling with prevalent face localization, hematologic and liver diseases and only in 2% of cases with extracutaneous lesions including complete atrioventricular block. The Authors describe a case of LEN characterized by isolated atrioventricular block at birth and endocardial fibroelastosis without skin lesions in a preterm infant female. She was born from asymptomatic, ANA (Anti-Nuclear Antibodies) and ENA (anti-Extractable Nuclear Antigen) positive mother, with a previous miscarriage at the 5th week of gestation. PMID:22495199

De Leonibus, C; Lembo, C; Giliberti, P; Rojo, S; Foglia, M C; Giordano, L; Fratta, A



Retinoblastoma-independent antiproliferative activity of novel intracellular antibodies against the E7 oncoprotein in HPV 16-positive cells  

PubMed Central

Background "High risk" Human Papillomavirus strains are the causative agents of the vast majority of carcinomas of the uterine cervix. In these tumors, the physical integration of the HPV genome is a frequent, though not invariable occurrence, but the constitutive expression of the E6 and E7 viral genes is always observed, suggesting key roles for the E6 and E7 oncoproteins in the process of malignant transformation. The "intracellular antibody" technology using recombinant antibodies in single-chain format offers the possibility of targeting a protein in its intracellular environment even at the level of definite domains thus representing a valuable strategy to "knock out" the function of specific proteins. Methods In this study, we investigate the in vitro activity of two single-chain antibody fragments directed against the "high-risk" HPV 16 E7 oncoprotein, scFv 43M2 and scFv 51. These scFvs were expressed by retroviral system in different cell compartments of the HPV16-positive SiHa cells, and cell proliferation was analyzed by Colony Formation Assay and EZ4U assay. The binding of these scFvs to E7, and their possible interference with the interaction between E7 and its main target, the tumor suppressor pRb protein, were then investigated by immunoassays, PepSet™technology and Surface Plasmon Resonance. Results The expression of the two scFvs in the nucleus and the endoplasmic reticulum of SiHa cells resulted in the selective growth inhibition of these cells. Analysis of binding showed that both scFvs bind E7 via distinct but overlapping epitopes not corresponding to the pRb binding site. Nevertheless, the binding of scFv 43M2 to E7 was inhibited by pRb in a non-competitive manner. Conclusions Based on the overall results, the observed inhibition of HPV-positive SiHa cells proliferation could be ascribed to an interaction between scFv and E7, involving non-pRb targets. The study paves the way for the employment of specific scFvs in immunotherapeutic approaches against the HPV-associated lesions.



Segmentation of anti-nuclear antibody images based on the watershed approach  

Microsoft Academic Search

Fluorescence patterns at present are usually examined laboriously by experienced physicians through manually inspecting the slides with the help of a microscope. The readings in indirect immunofluorescene (IIF) usually suffer from the disadvantages such as the inter-observer variability that limits the reproducibility. This study proposes a segmented method based on the watershed algorithm to detect the edges of HEp-2 cells

Chung-Chuan Cheng; Jin-Shiuh Taur; Tsu-Yi Hsieh; Chin-Wang Tao



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

Technology Transfer Automated Retrieval System (TEKTRAN)

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


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



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


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



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



The clinical significance of anti-cyclic citrullinated peptide antibody in primary Sjögren syndrome.  


Anti-cyclic citrullinated peptide antibody (anti-CCP) is a specific marker for the diagnosis of rheumatoid arthritis. However, this antibody can be detected in other rheumatic diseases and even in healthy people. This study aims to determine the prevalence and the clinical significance of anti-CCP in patients with primary Sjögren syndrome (pSS). We analyzed the clinical and laboratory data of 95 patients with pSS by retrospective review of their medical records. Anti-CCP was measured by ELISA kit. Anti-CCP, rheumatoid factor (RF), anti-nuclear antibody, anti-Ro and anti-La antibodies, and clinical data were investigated. We analyzed clinical and serologic characteristics of anti-CCP-positive patients. Twenty-one patients (22.1%) had positive anti-CCP (mean titer 61.6 ± 15.6 U/ml) and 40 patients (42.1%) had positive RF (mean titer 98.8 ± 22.7 IU/ml). Seventy-nine patients (83.1%) had arthralgia, and 31 patients (32.6%) had non-erosive arthritis on physical examination and radiologic images. Anti-CCP-positive patients had more frequently positive RF (71.4% vs. 41.8%, P = 0.01) and anti-Ro antibody (85.7% vs. 60.8%, P = 0.03). Anti-CCP-positive patients had non-erosive arthritis more frequently than anti-CCP-negative patients (76.1% vs. 21.6%, P < 0.01). The prevalence of anti-CCP was 22.1% in pSS, and anti-CCP was associated with non-erosive arthritis, and positivity of RF and anti-Ro antibody. PMID:22205381

Kim, So-Mi; Park, Eugene; Lee, Jung-Hwa; Lee, Sang-Heon; Kim, Hae-Rim



Induction of a cross-reactive idiotype dextran-positive antibody response in two IgH-Cb mouse strains treated with anti-J558 cross- reactive idiotype antibodies  

PubMed Central

The effect of IdX-specific rabbit and allogeneic antiidiotype antibodies (Ab2) was investigated in vivo in Igh-Cb mouse strains with respect to the induction of a cross-reactive idiotype (IdX)-positive anti-alpha (1-3) Dextran (Dex) response. These C.B20 and C57Bl/6 mice have an allotype-linked incapacity to respond with IdX-positive anti- alpha (1-3) Dex antibodies upon conventional immunization with Dex B1355. 7 d after the rabbit Ab2 injections, IdX-positive Ig (Ab3) and IdX-positive anti-alpha (1-3) Dex antibodies (Ab1') were detected in the sera of each tested mouse. The affinity-purified Ab1' were idiotypically indistinguishable from reference BALB/c IdX-positive myeloma proteins and BALB/c anti-alpha (1-3) Dex antibodies (Ab1) in a competitive inhibition radioimmunoassay, while Ab3 Ig appeared idiotypically deficient and did not bind to Dex. The response to the alpha (1-6) linkage of Dex was not affected in these mice. A large fraction of the Ab1' and Ab3 responses of both mouse strains were of the IgG1 class. The Ab1' antibodies differed from BALB/c Ab1 by lower relative binding to five of eight tested Dex, and by expressing the Igh4b allotype determinants on the IgG1 antibodies. This study identifies the products of a VHDex gene that appears to be under regulatory control in the Ighb mice. Its association with the b haplotype suggests that this gene may differ structurally from the BALB/c VHDex gene.



Antibodies to salivary duct cells, and other autoantibodies, in patients with Sj?gren's syndrome and other idiopathic autoimmune diseases  

PubMed Central

Sera from thirty patients with Sjögren's syndrome were studied for the presence of antibodies to salivary duct cells. In sixteen cases (53%) a positive result was obtained. The antibodies were present in the IgG globulins, in the IgM globulins also in nearly 50% of the IgG-positive cases, and rarely in the IgA globulins. One-third of the antibodies proved to be complement-fixing. No antibodies were found in normal controls matched for sex and age. An antinuclear factor (ANF) was demonstrated in 77% of the sera. A rheumatoid factor was shown in 48% of the sera using a modified Waaler–Rose test and in 100% using a Latex fixation test. Antibodies to smooth muscle were present in 19%. Antibodies to skeletal muscle, gastric parietal cells, thyroid antigens, adrenocortex and mitochondria were found in frequencies which did not differ significantly from those in matched controls. No correlation was demonstrated between antibodies to salivary duct cells and any of the other antibodies mentioned. Antibodies to salivary duct cells could only be absorbed with salivary gland tissue and not with other tissues. Antibodies to salivary duct cells were also found in patients with rheumatoid arthritis (22%), systemic lupus erythematosus (SLE) (18%) and myasthenia gravis (11%). They were extremely rare in patients with pernicious anaemia, autoimmune thyroiditis and idiopathic adrenocortical insufficiency. The antibodies could not be confirmed as being directed against the patient's own parotid tissue, probably due to loss of antigenic determinants as a result of the disease process. However, other findings support the opinion that Sjögren's syndrome is an idiopathic autoimmune disease.

Feltkamp, T. E. W.; van Rossum, A. L.



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


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


Prevalence and Clinical Characteristics of Recently Diagnosed Type 2 Diabetes Patients with Positive Anti-Glutamic Acid Decarboxylase Antibody  

PubMed Central

Background Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in ?-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes. Methods We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics. Results The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups. Conclusion The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.

Hwangbo, Yul; Kim, Jin Taek; Kim, Eun Ky; Khang, Ah Reum; Oh, Tae Jung; Jang, Hak Chul; Park, Kyong Soo; Kim, Seong Yeon; Lee, Hong Kyu



Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases.  


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 from healthy individuals (HI) have been reported to have a positive ANA test, the majority of which are directed to the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis of SARD, the reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test, significantly reduces the specificity and the positive likelihood of the ANA test. This has significant implications for diagnostic algorithms involving the detection of ANA. We summarize the current knowledge of anti-DFS70 antibodies and their impact on ANA testing. We also suggest a test algorithm which considers the DFS pattern and the presence of anti-DFS70 antibodies. In addition, we describe a novel method based on immunoadsorption of anti-DFS70 antibodies, which increases the specificity of the ANA HEp-2 test for SARD and which has the potential to overcome a significant limitation of the ANA HEp-2 assay. PMID:22100330

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



Antibodies from patients with connective tissue diseases bind specific subsets of cellular RNA-protein particles.  

PubMed Central

We characterized the RNA-containing antigens precipitated by sera from 260 patients with positive antinuclear antibodies. 49 individuals, most of whom had systemic lupus erythematosus or Sjögren's syndrome, possessed antibodies that precipitated the previously identified RNP, Sm, Ro, and La antigens either singly or in combinations. These antigens, which are located on discrete sets of small nuclear or cytoplasmic RNA-protein particles, exhibited a number of antigenic interrelationships. One patient's serum recognized a new particle containing a small RNA which we have called Th; it also precipitated the Ro complexes. Other patients with systemic lupus erythematosus, hepatitis B virus infection, juvenile rheumatoid arthritis, myositis, and rheumatoid arthritis had antibodies that precipitated specific subsets of ribosomal RNA and transfer RNA. One patient's serum contained a monoclonal immunoglobulin G that precipitated ribosomes. Most of these antibodies identified antigenic determinants constituted at least in part of protein. The specificity of the proteins bound to particular cellular RNA, probably explains the exquisite precision with which antibodies from rheumatic disease patients discriminate among RNA subsets. Such sera should be useful probes for investigating specific roles that different RNA and RNA-protein complexes play in cellular metabolism. Images

Hardin, J A; Rahn, D R; Shen, C; Lerner, M R; Wolin, S L; Rosa, M D; Steitz, J A



Incidence and clinical correlation of anticentromere antibody in Thai patients  

Microsoft Academic Search

Anticentromere antibodies (ACA) are useful in assessing and classifying patients with mild variant of systemic sclerosis called\\u000a calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias (CREST) syndrome. From their prognostic\\u000a significance, we are interested in the prevalence and disease correlation in Thai patients. A total of 3,233 serum samples\\u000a of patients with any musculoskeletal symptoms were sent for antinuclear antibody determination

Krisaree Pakunpanya; Oravan Verasertniyom; Monchand Vanichapuntu; Prapaporn Pisitkun; Kitti Totemchokchyakarn; Kanokrat Nantiruj; Suchela Janwityanujit



Antibodies in scleroderma: Direct pathogenicity and phenotypic associations  

Microsoft Academic Search

Scleroderma is an autoimmune disease involving endothelial cell damage and fibroblast overproduction of extracellular matrix.\\u000a Several autoantibodies present in the sera of patients with scleroderma, including anti-endothelial cell, antifibroblast,\\u000a anti-matrix metalloproteinase, and antifibrillin-1 antibodies, may directly contribute to disease pathogenesis. Scleroderma\\u000a also is characterized by the presence of antinuclear and antinucleolar antibodies, which correlate with particular phenotypes.\\u000a These include antitopoisomerase-I,

Lorinda Chung; Paul J. Utz



Delayed Development of Pulmonary Hemorrhage in a Patient with Positive Circulating Anti-Neutrophil Cytoplasmic Antibody: A Clinical Dilemma  

PubMed Central

Detection of circulating anti-neutrophil cytoplasmic antibody (ANCA) provides a powerful clue in the diagnosis of vasculitis, but the clinical interpretation of the results is difficult in some cases. Here, we describe the case of a 65-year-old man who underwent hemodialysis due to focal segmental glomerulosclerosis and abruptly developed hemoptysis 14 years after a renal biopsy. At the time of the biopsy, computed tomography (CT) showed interstitial shadows in the lungs and pleural thickening, indicating pneumoconiosis that was accompanied by tuberculosis. Circulating myeloperoxidase-ANCA (10.5–32.5 U/ml) was subsequently noted, but the significance of this observation was unclear due to the preexisting disorders in the lungs and kidneys. Potent immunosuppressive therapies were avoided because of the pulmonary lesions and decreased renal function. There were few changes noted on follow-up CT, but infiltrative shadows emerged in the bilateral lungs, consistent with hemoptysis. The hemorrhagic shadows completely disappeared shortly after initiation of steroid therapy, with normalization of the serum ANCA level. Herein, we report this case, with an emphasis on the clinical dilemma faced in deciding the appropriate treatment. The findings in the case provide deep insights into clinical management of ANCA-positive patients.

Imai, Toshimi; Takeda, Shin-ichi; Kawaguchi, Kazuo; Chaki, Yuko; Morishita, Yoshiyuki; Akimoto, Tetsu; Muto, Shigeaki; Kusano, Eiji



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.



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


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



Conjugates of folate and anti-T-cell-receptor antibodies specifically target folate-receptor-positive tumor cells for lysis.  

PubMed Central

High-affinity folate receptors (FRs) are expressed at elevated levels on many human tumors. Bispecific antibodies that bind the FR and the T-cell receptor (TCR) mediate lysis of these tumor cells by cytotoxic T lymphocytes. In this report, conjugates that consist of folate covalently linked to anti-TCR antibodies are shown to be potent in mediating lysis of tumor cells that express either the alpha or beta isoform of the FR. Intact antibodies with an average of five folate per molecule exhibited high affinity for FR+ tumor cells but did not bind to FR- tumor cells. Lysis of FR+ cell lines could be detected at concentrations as low as 1 pM (approximately 0.1 ng/ml), which was 1/1000th the concentration required to detect binding to the FR+ cells. Various FR+ mouse tumor cell lines could be targeted with each of three different anti-TCR antibodies that were tested as conjugates. The antibodies included 1B2, a clonotypic antibody specific for the cytotoxic T cell clone 2C; KJ16, an anti-V beta 8 antibody; and 2C11, an anti-CD3 antibody. These antibodies differ in affinities by up to 100-fold, yet the cytolytic capabilities of the folate/antibody conjugates differed by no more than 10-fold. The reduced size (in comparison with bispecific antibodies) and high affinity of folate conjugates suggest that they may be useful as immunotherapeutic agents in targeting tumors that express folate receptors.

Kranz, D M; Patrick, T A; Brigle, K E; Spinella, M J; Roy, E J



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

Microsoft Academic Search

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




Dual positivity of hepatitis B surface antigen and anti-hepatitis C virus antibody and associated factors among apparently healthy patients of Ekiti State, Nigeria.  


There are few studies on health-facility based prevalence rates for dual hepatitis B virus-hepatitis C virus (HBV-HCV) infection on a state-wide scale in Nigeria. In this study we determined the state-wide prevalence rate of dual positivity of hepatitis B surface antigen and anti-HCV antibody among hospital patients of Ekiti State, Nigeria, and identified associated factors. Consenting apparently-healthy patients visiting health centers in all local government area (LGA) headquarters of Ekiti State were consecutively selected to a total of 2000 individuals. Patient demographic data pertinent to HBV and HCV transmission were obtained using a structured questionnaire. Subsequently, serum samples prepared from the aseptically collected blood was tested for the presence of both HBsAg and anti-HCV antibody using DiaSpot test strips. The results were analyzed using binary logistic regression. Dual positivity of 7.40% was recorded among the study participants, with 9.80% and 12.80%, respectively, testing positive for HBsAg and anti-HCV antibody. The study patients were, however, most likely to be anti-HCV antibody positive. Nine of the 10 factors studied were independently associated with dual positivity. Five of these, in descending order of odds ratio, were: illiteracy (15.76, p=0.001); having ?4 sexual partners (9.46, p=0.001); age range of 35-44?y (8.46,p=0.001); farming (7.33, p=0.001); and "not at all" to use of condoms during sexual intercourse (4.39, p=0.001). The dual positivity rate was relatively high, with unprotected sexual intercourse as the most probable mode of acquisition of HBV and HCV by the seropositive study participants. PMID:23171358

Oje, Opeyemi James; Sule, Waidi Folorunso; Famurewa, Diran



Prevalence, clinical features and treatment outcomes of patients with myasthenia gravis positive for antibodies to muscle-specific kinase in Thailand.  


A small but variable subgroup of patients with myasthenia gravis (MG) who have antibodies to muscle-specific kinase (MuSKAb-MG) can present with distinct phenotypes and are often treatment-resistant. The prevalence, clinical phenotypes and outcomes of treatment of patients with MuSKAb-MG in Thailand were determined. Eight (16.3%) of the 49 patients with generalized MG who were negative for acetylcholine receptor antibodies (AChRAb) were positive for muscle-specific kinase antibodies. Most patients had predominant oculobulbar features and respiratory failure occurred in three. At follow up, three out of the seven patients who underwent thymectomy were in complete stable remission and four had improved and were on reduced immunosuppression medication, suggesting a possible benefit of thymectomy. PMID:23352351

Witoonpanich, Rawiphan; Dejthevaporn, Charungthai; Pulkes, Teeratorn; Tunlayadechanont, Supoch; Boonkongchuen, Pairoj; Pongpakdee, Sunsanee; Vincent, Angela



Conjugates of Folate and Anti-T-Cell-Receptor Antibodies Specifically Target Folate-Receptor-Positive Tumor Cells for Lysis  

Microsoft Academic Search

High-affinity folate receptors (FRs) are expressed at elevated levels on many human tumors. Bispecific antibodies that bind the FR and the T-cell receptor (TCR) mediate lysis of these tumor cells by cytotoxic T lymphocytes. In this report, conjugates that consist of folate covalently linked to anti-TCR antibodies are shown to be potent in mediating lysis of tumor cells that express

David M. Kranz; Todd A. Patrick; Kevin E. Brigle; Michael J. Spinella; Edward J. Roy



Coexistence of ANCA-associated glomerulonephritis and anti-phospholipase A2 receptor antibody-positive membranous nephropathy  

PubMed Central

Antibodies to myeloperoxidase (MPO) and proteinase 3 (PR3) have been demonstrated to mediate anti-neutrophil cytoplasmic antibody (ANCA)-associated disease. For membranous nephropathy, antibodies to the podocyte-expressed phospholipase A2 receptor (anti-PLA2R) are highly associated with disease activity and have been reported in at least 70% of patients with idiopathic membranous nephropathy (IMN). We present a case of a 56-year-old male with a 1 year history of hypertension, leg edema, and proteinuria, who presented with advanced renal failure and was found to have both ANCA-associated glomerulonephritis (GN) and IMN on kidney biopsy. Consistent with the idea that this is due to the chance occurrence of two independent diseases, we found both anti-MPO and anti-PLA2R antibodies in the patient's sera. Treatment with methylprednisolone, plasmapheresis, and cyclophosphamide resulted in improvement in kidney function and proteinuria, together with the simultaneous decrease in both autoantibodies. This is the first demonstration of two pathogenic antibodies giving rise to ANCA-associated GN and IMN in the same patient. It confirms the importance of classifying disease based upon the underlying mechanism, in addition to renal histopathology, to both optimize therapy and predict prognosis.

Ayalon, Rivka; Hasan, Nazia; Beck, Laurence H.; Salant, David J.; Barisoni, Laura; Skolnik, Edward Y.; Beara-Lasic, Lada



Antibody-mediated cellular cytotoxicity against Raji cells ADCC(RAJI): Evaluation of false positives in the detection of circulating immune complexes by Raji-cell assay  

Microsoft Academic Search

Raji-cell radioimmunoassay is a very sensitive and reproducible method for the detection of circulating immune complexes. Using a complement-independent, antibody-dependent cellular cytotoxicity assay against51Cr-labeled Raji cells, there is no correlation between activity against Raji cells and positivity in Raji-cell radioimmunoassay for circulating immune complexes in three sets of sera (from renal transplantation patients, multiparous women, and patients suffering from systemic

Mrinal K. Dasgupta; Thavisakdi Kovithavongs; Joy Schlaut; Bryan M. Longenecker; John B. Dossetor



Serological and clinical comparison of children and adults with anti-endomysial antibodies.  


We compared serological and clinical presentation of 38 adults (5 males, 33 females) and 37 children (15 boys, 22 girls) with anti-endomysial antibodies (AEA).AEA, antinuclear (ANA), anti-parietal (APA), anti-thyroid microsomal (ATMA), anti-thyreoglobulin (ATGA), anti-smooth muscle (SMA) and anti-mitochondrial (AMA) antibodies were detected by IIF. Anti-tissue transglutaminase (tTG), anti-extractable nuclear antigens (ENA) and anti-actin (AAA) antibodies were studied by ELISA. There were no differences in frequency of ANA, APA, ATGA, SMA, AMA and AAA in children and adults. ATMA (p < 0.001) and anti-ENA (p < 0.05) positivity were more frequently found in adults. Anti-Ro/SSA had 7/38 adults and 1/37 children (p < 0.05). Adults had more frequently silent form of celiac disease associated with autoimmune diseases (p < 0.001). We are the first to demonstrate that in spite of no difference in ANA positivity in adults and children, ANA in adults more frequently target ENA, especially Ro/SSA antigen. The reason for this ANA specificity could be the longer gluten exposure in adults. PMID:17243009

Bonaci-Nikolic, Branka; Andrejevic, Sladjana; Radlovic, Nedeljko; Davidovic, Ivana; Sofronic, Ljiljana; Spuran, Milan; Micev, Marjan; Nikolic, Milos M



Increased detection of Sin Nombre hantavirus RNA in antibody-positive deer mice from Montana, USA: evidence of male bias in RNA viremia.  


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. PMID:24064796

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



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.



Pulmonary thromboembolism associated with procainamide induced lupus syndrome and anticardiolipin antibodies  

Microsoft Academic Search

Procainamide is the commonest cause of a drug induced lupus syndrome. Long term administration of this compound may induce a variety of immunological abnormalities, including antinuclear antibodies. Uncommonly, 'lupus anticoagulants' have been demonstrated in the absence of other evidence of drug induced lupus. Details of a 67 year old man who developed not only drug induced lupus but also antiphospholipid

R A Asherson; J Zulman; G R Hughes



Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test.  


Abstract Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT. PMID:24102149

Hron, Gregor; Knutson, Folke; Thiele, Thomas; Althaus, Karina; Busemann, Christoph; Friesecke, Sigrun; Greinacher, Andreas; Lubenow, Norbert



False positive reactivity of a substance P-antibody in the ectodermal/epithelial plug of the nose, ear, eye and perineum of the human and mouse fetuses.  


Epithelial/ectodermal plug formation in the developing nose, ear, and eye regions is followed by canalization/recanalization mediated by cell death. However, the mechanism is not well understood. Recently, substance P (SP)-mediated cell death, rather than cell apoptosis, has been reported in neuronal and non-neuronal cells. Horizontal paraffin sections of 5 human fetuses at 15-16 weeks of gestation were used to examine the entire area of the nose, ear, eye and perineum with immunohistochemistry for SP and its receptor neurokinin-1 (NK-1), and protein gene product (PGP) 9.5 and S100 protein to identify whether the positive cells had neural origins. The deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) method was also conducted to identify apoptosis. Four SP antibodies were commercially obtained and compared the results. In addition, using the same antibodies for SP, those results were compared with fetal mouse heads (E14-17). Substance P immunoreactivity of one of the 4 antibodies (sc9758) was clearly found in the nasal plug, the epithelium of the anterior nasal cavity, the entire excretory tear duct, the marginal palpebral conjunctiva, the auditory meatal plug, the parotid duct, the external urethral orifice and, the preputial lamella along the future prepuce. Immunoreactivity was usually seen in enlarged round cells in humans. In fetal mouse heads, in spite of negative reaction in all these sites, the midline epithelial seam at the palate fusion and the oral epithelium especially at and near the tooth germ specifically reacted with the sc9758. Nevertheless, the other 3 antibodies did not react at any of those sites both in human and mouse fetuses. NK-1 receptor-positive cells were seen in the nose and meatal plugs and preputial lamella, but not in the tear duct. S100 protein, PGP 9.5, and TUNEL method all demonstrated negative reactivity at any sc9758-positive sites. Consequently, the present immunoreactivity of the sc9758 antibody seemed to be false positive, but it was likely to react with a specific substance in the epithelial or ectodermal cell because of the clearly restricted staining. Which substance it crossed remains unknown. PMID:20882765

Masumoto, Hiroshi; Katori, Yukio; Kawase, Tetsuaki; Cho, Baik Hwan; Murakami, Gen; Shibata, Shunichi; Matsubara, Akio



[A case of neuromyelitis optica associated with anti-aquaporin 4 antibody and other autoantibodies].  


We report a patient with optic neuropathy and longitudinally extensive myelitis associated with anti-aquaporin 4 (AQP4) antibody and other autoantibodies. An 89-year-old woman presented with progressive numbness and weakness of the extremities which had acutely developed. She also complained of neck pain and gait disturbance. The results of a general physical examination were unremarkable. Neurologic examination disclosed right optic atrophy, an absence of touch sensation, pain, and muscular weakness in all her extremities. Her deep tendon reflexes were decreased, and the Babinski sign was bilaterally positive. Immunoserologic study yielded positive titers for anti-nuclear antibody (ANA), anti-double-stranded DNA, anti-Sjögren syndrome (SS)-A, anti-SS-B, and anti-ribonucleoprotein (RNP) antibodies. A lumbar cerebrospinal fluid examination showed a protein concentration of 54 mg/dL, a glucose concentration of 50 mg/dL (simultaneous blood concentration, 140 mg/dL), and a cell count of 2/mm(3). Chest radiography revealed interstitial pneumonia. Magnetic resonance imaging (MRI) of the cervical spine showed spondylotic cervical canal stenosis with cord impingement. T2-weighted MR images demonstrated increased signal intensity extending from C2 to C6, while contrast enhancement was noted in T1-weighted MR images upon gadolinium-DTPA administration. We suspected longitudinally extensive myelitis associated with the autoimmune disorders systemic lupus erythematosus and Sjögren syndrome. After intravenous methylprednisolone administration, her neurologic abnormalities gradually decreased, while MRI no longer showed increased signal or contrast enhancement. Anti-AQP4 antibody titers were positive. We consider that this patient had a neuromyelitis optica (NMO) spectrum disorder which was associated with systemic autoimmune disease. The possibility of NMO should be considered in similar patients with autoimmune disease, and anti-AQP4 antibody should be assessed. PMID:23269030

Maruta, Kyoko; Sonoda, Yoshito; Uchida, Yuichi; Takahashi, Toshiyuki; Fukunaga, Hidetoshi



A rare case of recurrent pregnancy loss associated with high-titer positivity for perinuclear anti-neutrophilic cytoplasmic antibodies  

PubMed Central

We present a case of recurrent pregnancy loss associated with unusual constellation of utoimmunity-related features such as hypertension, severe hrombocytopenia, hypothyroidism and persistent high titers of perinuclear antineutrophilic cytoplasmic antibodies. Her clinical features did not fit into a particular diagnosis of vasculitides, systemic lupus erythematosis (SLE) or other known autoimmune diseases where this autoantibody is found in high titers. We report the unusual association of this autoantibody with recurrent early fetal demise in this case.

Vasudeva, Akhila; Acharya, Raviraja V; Kumar, Pratap



Elevated Anticardiolipin Antibody Titer Is a Stroke Risk Factor in a Multiethnic Population Independent of Isotype or Degree of Positivity  

Microsoft Academic Search

Background and Purpose—Previous studies have produced conflicting results regarding the putative association between anticardiolipin antibodies (aCL) and infarction in the general stroke population. These inconsistencies may be a function of sample size and methodological differences among the studies. The purpose of the present study, the largest case-control study of this issue to date, was to assess aCL status as an

Jacob H. Rand; Xiao-Xuan Wu; Jesse Weinberger; Deborah R. Horowitz; Martin E. Goldman; James H. Godbold


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



Anti-Annexin V Antibodies: Association with Vascular Involvement and Disease Outcome in Patients with Systemic Sclerosis  

PubMed Central

Background: Systemic Sclerosis (SSc) is characterized by skin thickening, fibrosis and vascular obliteration. The onset and course are heterogeneous. Prominent features include autoimmunity, inflammation and vascular damage. Aim of study: To measure the level of serum Anti-Annexin V antibodies in SSc patients and to study its significance in relation to vascular damage in these patients. Patients and methods: Twenty patients with SSc (12 with diffuse SSc and 8 with the limited form) and 10 healthy age and sex matched volunteers as controls were all subjected to routine laboratory testing and immunological profiling including antinuclear, anti-Scl-70, anticentomere, anticardiolipin antibodies and anti-annexin V antibodies titres. Vascular damage was assessed by clinical examination and assessment of the disease activity score, nailfold capillaroscopy and colour flow Doppler of the renal arteries; Doppler echocardiography was used for assessing pulmonary hypertension. Results: Anti-annexin V antibodies were detected in 75% of patients. Comparisons between anti-annexin V in diffuse and limited subgroups showed no significance; however a statistically significant positive correlation was found between Anti-annexin V titre and the degree of vascular damage in SSc patients. Anti-annexin V increased significantly in patients with severe vascular damage in comparison with those less affected (15.3 ± 6.6 vs. 11.25 ± 3.6, P < 0.05). A significant positive correlation was found between Anti-annexin V titre and both the ACL titre (r = 0.79, P < 0.001) and the resistive index of the main renal artery (r = 0.42, P < 0.05). Conclusion: Anti-annexin V antibodies were significantly present in sera of patients with SSc. Patients with more severe forms of vascular damage had higher titres of these antibodies. Anti-annexin V antibodies are a sensitive predictor of vascular damage in SSc and could serve as a useful parameter in discriminating patients with a higher risk of vascular affection from those without.

Habeeb, Reem A.; Mansour, Howaida E.; Abdeldayem, Aya M.; Abo-shady, Rania A.; Hassan, Iman A.; Saafan, Nazek K.; Aly, Dalia G.



Protection from clinical disease against three highly virulent strains of Newcastle disease virus after in ovo application of an antibody-antigen complex vaccine in maternal antibody-positive chickens.  


Worldwide, Newcastle disease (ND) remains one of the most economically important diseases of poultry. Current vaccination strategies for commercial poultry include the use of inactivated and live ND vaccines that typically induce protection against virulent field viruses. Here, we tested the efficacy of an antigen-antibody complex (AAC) ND vaccine delivered in ovo. Commercial maternal antibody-positive broiler chickens (Gallus domesticus) were vaccinated in ovo with an AAC vaccine composed of live B1-LaSota Newcastle disease virus (NDV) complexed with NDV-specific antiserum, and then they were challenged at weekly intervals after hatch. Challenge viruses included three exotic ND disease (END) viruses: the neurotropic strain Texas GB NDV-92-01 (TxGB) and two viscerotropic isolates, one isolate from the 2002-2003 outbreak in California (California 2002 isolate S212676 [CA]) and the other isolate from a 1997 END outbreak in South Korea (South Korea 94-147 [SK]). Results demonstrate that maternal antibody was able to provide approximately 50% protection in either vaccinated or control chickens at 7 days of age after TxGB challenge. However, with challenge at > or = 14 days, most control birds died, whereas all AAC-vaccinated birds were protected. Challenge with the CA or SK viruses in chickens at 28 days of age resulted in 100% protection of vaccinated birds, whereas all control birds died. In addition, AAC-vaccinated birds displayed decreased incidence of viral shedding in oral and cloacal swabs than control birds. Antibody titers were significantly (P < 0.05) higher in vaccinated chickens, as determined by enzyme-linked immunosorbent assay and hemagglutinin-inhibition tests, than in nonvaccinated controls. Together, these results demonstrate the efficacy of AAC vaccines delivered in ovo to protect commercial poultry. PMID:23050473

Kapczynski, Darrell R; Martin, Alison; Haddad, Eid E; King, Daniel J



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

Microsoft Academic Search

1.?The immune responses induced by recombinant plasmids containing Newcastle disease virus (NDV) F (pVAX.nd.f) or HN ( genes separately or in combination in bi-cistronic ( 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

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



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


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



Cellular relationships of paranodal Marchi-positive bodies studied with monoclonal antibodies against partially degraded CNS myelin fragments  

Microsoft Academic Search

Summary Histochemical and electron microscopical studies have shown that Marchi-positive bodies in the normal mammalian CNS are associated with paranodal regions and it has been proposed that the formation of Marchi-positive bodies represents a step in the catabolic events of normal myelin turnover. After a two-step density gradient ultracentrifugation a light ‘floating fraction’ highly enriched in these structures can be

H. Persson; C.-H. Berthold



Positive correlation between replication rate and pathotype of Marek’s disease virus strains in maternal antibody negative chickens  

Technology Transfer Automated Retrieval System (TEKTRAN)

Pathotyping of new field strains of MDV requires both a long period of time and a large number of birds. Confirming a positive correlation of virus replication and pathotype may lead to faster and cheaper alternative pathotyping methods or as a screening assay for choosing isolates to be pathotyped....


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.



Circulating anti-actin and anti-ATP synthase antibodies identify a sub-set of patients with idiopathic nephrotic syndrome  

PubMed Central

Idiopathic nephrotic syndrome (iNS) with resistance or dependence to steroids is a common disease in children but in spite of an increasing clinical impact its pathogenesis is unknown. We screened for the presence of circulating antibodies against glomerular (podocytes, mesangium) and tubular cells (tubular epithelia) a cohort of 60 children with iNS including 8 patients with a familial trait of iNS or with proven mutation of NPHS1-NPHS2 and 12 with good sensitivity to steroids. Positive sera were found in 8 cases, all belonging to the category without familial trait/molecular defects. The targets of antibodies were characterized with Western blot and MALDI-Mass utilizing ?-hexyl cell extracts separated with two-dimensional electrophoresis. In all cases antibodies of the IgM class were directed against ATP synthase ? chain alone (4 cases) or in combination with actin (3 cases); one child presented IgG against aldose reductase. The clinical picture was nephrotic syndrome with steroid resistance or dependence and variable cyclosporin sensitivity; 3 patients developed end stage renal failure. The basic pathology picture was focal segmental glomerulosclerosis (FSGS) in 4 cases and mesangial proliferative glomerulonephrites with deposition of IgM in 2. Overall, patients with circulating auto-antibodies could not be readely differentiated on clinical grounds with the exception of 3 children who developed positivity for antinuclear antibodies during the follow-up. Affinity-purified IgM from one patient who underwent plasmapheresis for therapeutical pourposes (but not from a normal pool) induced proteinuria in Sprague-Dawley rats and concomitant human IgM deposition within glomeruli. This is the first report of circulating anti-actin/ATP synthase ? chain antibodies in a subset of patients with iNS. Both pathological significance and clinical impact given by the presence of these antibodies and the relationship with other conditions such as lupus-erythematosus, characterized by their presence, must be defined.

Musante, L; Candiano, G; Bruschi, M; Santucci, L; Carnemolla, B; Orecchia, P; Giampuzzi, M; Zennaro, C; Sanna-Cherchi, S; Carraro, M; Oleggini, R; Camussi, G; Perfumo, F; Ghiggeri, G M



Presence of IgG Anti-gp160/120 Antibodies Confers Higher HIV Capture Capacity to Erythrocytes from HIV-Positive Individuals  

PubMed Central

Background HIV binding has been demonstrated in erythrocytes from HIV-positive and HIV-negative individuals. However, the presence of immunoglobulins G anti-HIV (IgG anti-HIV) in erythrocytes from HIV-positive individuals is still to be elucidated. Moreover, the capacity of erythrocytes from HIV-positive individuals to capture an additional amount of HIV has not been studied. Indeed, it is unknown if HIV binding to erythrocytes in HIV-positive persons could have consequences on the cell-free infectious virus available. Methodology/Principal Findings IgGs anti-HIV associated to erythrocytes were found in 77.3% (58/75) of the HIV-positive individuals studied and the IgGs anti-gp160 and anti-p24 were the most frequently found. We found a positive association between detectable plasma viral load (pVL) and presence of IgGs anti-HIV associated to erythrocyte (p<0.005), though the anti-p24/160 were present with or without detectable pVL. The HIV capture capacity was higher in erythrocytes from HIV-positive than HIV-negative individuals (p<0.0001). Furthermore, among the HIV-positive individuals the higher viral capture capacity was associated with the presence of anti-gp160/gp120 on erythrocytes. Moreover, the viral capture by erythrocytes was independent of pVL (rho?=?0.022, p?=?0.8817). Additionally, reduction of cell-free infectious virus and available viral load was observed in the presence of erythrocytes from HIV-positive individuals. Conclusions/Significance Results suggest that in HIV-positive individuals, erythrocytes are capable of capturing high amounts of HIV by the presence of IgGs anti-gp160/120 on their membranes and this may produce a reduction in the available free virus. Finally, the current measurement of pVL would underestimate the real viral quantity due to the HIV binding through specific antibodies to erythrocytes.

Garcia, Maria Noe; dos Ramos Farias, Maria Sol; Fazzi, Lucia; Grasso, Daniel; Rabinovich, Roberto Daniel; Avila, Maria Mercedes



The Effect of Precipitation on the Transmission of Japanese Encephalitis (JE) Virus in Nature: A Complex Effect on Antibody-Positive Rate to JE Virus in Sentinel Pigs  

PubMed Central

Japanese encephalitis (JE) is one of the most important mosquito-borne viral diseases in Asia. Pigs are a natural host and the amplifier of JE virus. The sero-conversion rate to JE virus in sentinel pigs reflects the activity of JE virus in the region. We analyzed whether precipitation has any effect on the sero-conversion rate to JE virus in sentinel pigs. Linear regression analysis was performed to determine the correlations between the levels of precipitation and sero-conversion rates to JE virus, in the entire year and during summertime over the period of 32 years from 1969 to 2000. The levels of the annual and summertime precipitation demonstrated statistically significant positive correlations with sero-conversion rates for the whole of the country and for some regions in Japan. The levels of the summertime precipitation, on the other hand, demonstrated statistically significant inverse correlations with the sero-conversion rates in other regions. Further, the levels of precipitation during preceding 10-day periods from days 1–40 before blood collection showed inverse correlation with antibody-positive rates in some regions. The results indicate that the relationship between the annual and summertime precipitation, and the sero-conversion rate to JE virus is complex; both positive and inverse effects are demonstrated depending on the regions.

Kurane, Ichiro; Shibasaki, Ken-ichi; Kotaki, Akira; Hijioka, Yasuaki; Takasaki, Tomohiko



Overcoming a “Probable” Diagnosis in Antimitochondrial Antibody Negative Primary Biliary Cirrhosis: Study of 100 Sera and Review of the Literature  

Microsoft Academic Search

Serum anti-mitochondrial antibodies (AMA) are the serological hallmark of primary biliary cirrhosis (PBC), yet up to 15% of\\u000a PBC sera are AMA negative at routine indirect immunofluorescence (IIF) while being referred to as “probable” cases. The diagnostic\\u000a role of PBC-specific antinuclear antibodies (ANA) remains to be determined. We will report herein data on the accuracy of\\u000a new laboratory tools for

Nicola Bizzaro; Giovanni Covini; Floriano Rosina; Paolo Muratori; Elio Tonutti; Danilo Villalta; Fiorenza Pesente; Maria Grazia Alessio; Marilina Tampoia; Antonio Antico; Stefan Platzgummer; Brunetta Porcelli; Lucia Terzuoli; Marco Liguori; Danila Bassetti; Ignazio Brusca; Piero L. Almasio; Giuseppe Tarantino; Chiara Bonaguri; Paolo Agostinis; Elena Bredi; Renato Tozzoli; Pietro Invernizzi; Carlo Selmi


Assessing the within-herd prevalence of cows antibody-positive to bovine viral diarrhoea virus with a blocking ELISA on bulk tank milk.  


Milk samples from 135 herds in Brittany were tested by a blocking ELISA for antibodies to bovine viral diarrhoea virus (BVDV) and used to assess the relationship between the bulk milk result and the within-herd prevalence of antibody-positive lactating cows. This relationship was first quantified by using a general linear model and controlling for the number of cows contributing milk to the bulk tank, for the percentage of primiparous cows in the herds and for the number of milkings contributing to the bulk tank. Receiver operating characteristic (ROC) analysis was then used to define classes of percentage inhibition in the bulk milk associated with minimum intraclass and maximum between-class variances of the within-herd prevalence. Only the percentage inhibition of bulk milk had a significant positive effect on within-herd prevalence (R2 = 0.85). The ROC analysis provided three classes of bulk milk results corresponding to different expected levels of within-herd prevalence. Herds with bulk milk percentage inhibitions of 0 to 35 per cent, 35 to 60 per cent and 60 to 100 per cent had mean (sd) observed prevalences of 4.8 (5.7) per cent, 21.6 (14.6) per cent and 66.0 (29.3) per cent, respectively. Herds with a bulk milk inhibition of 0 to 35 per cent were expected to be BVDV-free. A herd with two consecutive bulk milk results four months apart of 60 per cent or more was likely to have a very high prevalence (median of 93 per cent) and could be suspected of harbouring an active infection. PMID:11554568

Beaudeau, F; Assié, S; Seegers, H; Belloc, C; Sellal, E; Joly, A



Limitations of a single-point evaluation of anti-MDA5 antibody, ferritin, and IL-18 in predicting the prognosis of interstitial lung disease with anti-MDA5 antibody-positive dermatomyositis.  


Autoantibodies against melanoma differentiation-associated gene 5 (MDA5) are important serological markers in dermatomyositis (DM) with rapidly progressive interstitial lung disease (ILD). Recent studies noted that anti-MDA5 antibody (anti-MDA5ab), ferritin, and IL-18 are useful biomarkers for evaluating the responses to treatment and the status of ILD in anti-MDA5ab-positive DM. In this study, we further studied the importance of anti-MDA5ab levels and of ferritin and IL-18 concentrations in our patients. These biomarkers could be sometimes useful for evaluating ILD status and/or predicting the prognosis in patients with anti-MDA5ab-positive DM with several exceptional cases. A single-point evaluation of anti-MDA5ab levels and of ferritin and IL-18 concentrations has limitations in predicting the prognosis of ILD with DM. We consider that the timing of initial therapy and the anti-MDA5ab isotype, in addition to the patient's age, are also crucial factors for predicting the prognosis. PMID:23250474

Muro, Yoshinao; Sugiura, Kazumitsu; Akiyama, Masashi



Reactivation of hepatitis B virus with mutated hepatitis B surface antigen in a liver transplant recipient receiving a graft from an antibody to hepatitis B surface antigen- and antibody to hepatitis B core antigen-positive donor  

PubMed Central

BACKGROUND Fresh-frozen plasma (FFP) may contain antibodies to hepatitis B surface antigen (HBsAg, anti-HBs). These anti-HBs may lead to a misinterpretation of the actual hepatitis B immune status. Furthermore, they may not only confer protection against hepatitis B virus (HBV), but may also favor the selection of HBsAg mutants. CASE REPORT We report a case of de novo HBV infection in a HBV-naïve recipient with alcoholic liver disease, who received a liver from a donor with antibodies to hepatitis B core antigen (HBcAg, anti-HBc) and anti-HBs. RESULTS A lookback investigation revealed the following: 1) Due to anti-HBs passively acquired through FFP, the recipient was considered immune to HBV and did not receive anti-HBV prophylaxis. 2) Within 1 year after transplantation he developed hepatitis B in absence of any elevated liver enzymes after the anti-HBs by FFP declined. 3) Despite an infection with HBV-containing wild-type HBcAg, the patient did not seroconvert to anti-HBc positivity. 4) The replicating HBV encoded two HBsAg mutations, first sQ129R and 4 months later sP127S. They map to the highly conserved “?” determinant of the HBsAg loop. CONCLUSION 1) Passive transfer of anti-HBs from FFP led to an erroneous pretransplant diagnosis of HBV immunity when the patient was in fact HBV-naïve. 2) HBsAg mutations might have been selected in escape from donor's actively produced anti-HBs and the recipient's anti-HBs by FFP might have favored this selection. 3) It is doubtful whether hepatitis B immunoglobulin could have prevented the reactivation. 4) Antiviral prophylaxis would have been crucial.

Blaich, Annette; Manz, Michael; Dumoulin, Alexis; Schuttler, Christian G; Hirsch, Hans H; Gerlich, Wolfram H; Frei, Reno



Anti-Nuclear Antibody Production and Immune-Complex Glomerulonephritis in BALB\\/c Mice Treated With Pristane  

Microsoft Academic Search

The pathogenesis of systemic lupus erythematosus is thought to be primarily under genetic control, with environmental factors playing a secondary role. However, it has been shown recently that intraperitoneal injection of pristane (2,6,10,14-tetramethylpentadecane) induces autoantibodies typical of lupus in BALB\\/c mice, a strain not usually considered to be genetically susceptible to the disease. In this study, the induction of autoimmune

Minoru Satoh; Anil Kumar; Yashpal S. Kanwar; Westley H. Reeves



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

Microsoft Academic Search

When monoclonal ANAs and non-ANAs generated from a genetically simplified mouse model of lupus, B6.Sle1, were recently compared, the ANAs exhibited three 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

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



Demonstration of a new antinuclear antibody (anti-RA33) that is highly specific for rheumatoid arthritis.  


Using immunoblot analysis with soluble nuclear extracts from HeLa cells, we identified autoantibodies to an antigen with a molecular weight of approximately 33,000 in 36% of 95 sera from rheumatoid arthritis patients, but in only 1 of 170 controls. The antigen, termed RA33, was resistant to DNase and RNase digestion but sensitive to proteinase K treatment. There was no discernible relation to other autoantibodies. Thus, this newly described autoantibody appears to be highly specific for rheumatoid arthritis. PMID:2597207

Hassfeld, W; Steiner, G; Hartmuth, K; Kolarz, G; Scherak, O; Graninger, W; Thumb, N; Smolen, J S



Mercury exposure, malaria, and serum antinuclear\\/antinucleolar antibodies in amazon populations in Brazil: a cross-sectional study  

Microsoft Academic Search

BACKGROUND: Mercury is an immunotoxic metal that induces autoimmune disease in rodents. Highly susceptible mouse strains such as SJL\\/N, A.SW, B10.S (H-2s) develop multiple autoimmune manifestations after exposure to inorganic mercury, including lymphoproliferation, elevated levels of autoantibodies, overproduction of IgG and IgE, and circulating immune complexes in kidney and vasculature. A few studies have examined relationships between mercury exposures and

Ines A Silva; Jennifer F Nyland; Andrew Gorman; Andre Perisse; Ana Maria Ventura; Elizabeth CO Santos; Jose M de Souza; CL Burek; Noel R Rose; Ellen K Silbergeld



Solving the deterrence problem: Western antinuclearism, strategic revisionism, and US arms control policy, 1979-1991  

SciTech Connect

This study is concerned with the changing domestic climate for nuclear weapons issues in the West during the 1980s. More specifically, it examines the impact of normative critiques of nuclear deterrence, as articulated by key elites in the US and various Western European democracies, on the formulation and conduct of American arms control policy between the signing of SALT 1 and the conclusion of the first START agreement. Two major schools of criticism are identified: (1) rooted in left-of-center elements of Western democratic politics, is described as antinuclearism; and (2) based in the conservative side of the political spectrum, is referred to as strategic revisionism. The first half of this study examines these two phenomena distinguishing prudential and normative dimensions of these schools. The second half examines the quite different postures taken by the two schools regarding prospective reform of the current nuclear regime, and traces the role of antinuclearist and revisionist advocacy in the debate over American arms control policy during the 1980s.

Leverett, F.L.



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



Tissue antibodies in idiopathic autoimmune haemolytic anaemia  

PubMed Central

Sera from patients with idiopathic autoimmune haemolytic anaemia (AIHA) were studied, by the immunofluorescent technique, for the presence of circulating organ-specific and non-organ-specific autoantibodies. In patients with warm AIHA there was an increased incidence in the non-organ-specific autoantibodies, compared to normal controls: In 15% of sera studied there were antinuclear antibodies detectable, and in 5% antimitochondrial antibodies were present. In cold AIHA, however, the frequency of these autoantibodies was not increased. The incidence of organ-specific autoantibodies was normal in both cold and warm AIHA. No correlation was found between the occurrence of these autoantibodies and pattern of serum immunoglobulin concentration, specific serological feature, or clinical manifestation. The significance of the increased incidence of tissue autoantibodies and their relation to autoimmune haemolytic anaemia remains to be elucidated, but in some way may be due to increased immunological reactivity.

Blajchman, M. A.



Serum anti-P53 antibodies and alpha-fetoprotein in patients with non-B non-C hepatocellular carcinoma.  


The rate of hepatocellular carcinoma (HCC) is increasing worldwide including Egypt. Non-B non-C HCC was reported in some countries. We aimed to investigate P53 antibodies and alpha-fetoprotein in patients with non-B non-C HCC in our region. In a case series study, included 281 patients with HCC and 20 patients with liver cirrhosis of matched age, sex and social factors were received for management at Tanta University Hospitals. Sera were tested for HCV and HBV markers by ELISA/PCR, alpha-fetoprotein (AFP) level and anti-p53 antibody were evaluated by ELISA. Antinuclear antibody, serum copper and iron were assessed in non-viral HCC. Liver scanning and biopsy were evaluated. Non-B non-C HCC patients were 13.87% of total. P53 antibody serum level in non-B non-C HCC patients showed insignificant difference (p>0.05) as compared to viral-associated HCC, while significant as compared to cirrhosis. They had significant decrease in serum AFP level (p<0.001) as compared to viral-associated HCC. Their tumors were mainly solitary, and have smaller-sizes. Sensitivity, specificity, PPV, NPV and accuracy test of anti P53 antibody positive patients were 91.52%, 84.63%, 90.34%, 80.2% and 74.8% respectively. It correlates positively with AFP, tumor size and staging, MELD score and Child-Pugh score. Non-B non-C HCC showed high serum prevalence of anti-p53 as viral-associated HCC suggesting an evidence of high onchogenecity. It appears of much benefit in diagnosis, follow up and differentiation from cirrhosis in presence of low levels of alpha-fetoprotein. PMID:23518665

El Azm, Abdel Raouf Abou; Yousef, Mohamed; Salah, Raafat; Mayah, Wael; Tawfeek, Salwa; Ghorabah, Hussien; Mansour, Nagwa



Chicken egg yolk antibodies against F18ab fimbriae of Escherichia coli inhibit shedding of F18 positive E. coli by experimentally infected pigs  

Microsoft Academic Search

F18ab and F18ac are antigenic variants of a colonizing fimbria commonly found on E. coli associated with postweaning diarrhea and edema disease in pigs. Chicken F18ab antibodies were obtained by immunising hens with purified F18ab fimbriae. For their in vitro characterisation antibodies were isolated from diluted egg yolks by ammonium sulfate precipitation. In vitro adhesion tests demonstrated that the chicken

H. Imberechts; P. Deprez; E. Van Driessche; P. Pohl



Resistance to recombinant alpha interferon therapy in idiopathic mixed cryoglobulinemia: reinduction of remission by natural alpha interferon both in antibody-positive and -negative patients.  


A subset of patients treated with recombinant interferon alpha-2a (rIFN-alpha 2a) for idiopathic mixed cryoglobulinemia (IMC) developed clinical resistance to therapy after a sustained response. Neutralizing antibodies to rIFN-alpha 2a were found in the sera of three out of four such patients, and in none of the patients who remained responsive to treatment. rIFN-alpha 2a neutralizing antibodies appeared in serum samples of the former three patients 1, 5 and 6 months before evidence for clinical resistance, respectively. Antibody titres to rIFN-alpha 2a were consistently higher than those to natural interferon (nIFN). In the fourth patient with clinical resistance, neutralizing antibodies could not be detected by a very sensitive bioassay in any of several serum samples taken before and after relapse. All the four patients could be reinduced into remission by the administration of nIFN-alpha. These data indicate that mechanisms other than the production of neutralizing antibodies can mediate acquired resistance to IFN therapy. Furthermore, both antibody-related and -unrelated resistance can be overcome by switching to different species of IFN-alpha. PMID:7863814

Casato, M; Antonelli, G; Maggi, F; Pucillo, L P; Di Lullo, L; Leoni, M; Currenti, M; Dianzani, F; Bonomo, L


Demonstration of Borna disease virus (BDV) in specific regions of the brain from horses positive for serum antibodies to BDV but negative for BDV RNA in the blood and internal organs  

Microsoft Academic Search

Sero- and molecular-epidemiological studies on Borna disease virus (BDV) infection show that BDV RNA is not always detected\\u000a in the peripheral blood mononuclear cells (PBMCs) from serum anti-BDV antibody-positive individuals such as horses, sheep,\\u000a cattle, cats, and humans. In this study we demonstrated BDV RNA signals by polymerase chain reaction only in restricted regions\\u000a of the brain from horses with

Katsuro Hagiwara; Noriko Momiyama; Hiroyuki Taniyama; Takaaki Nakaya; Nobuo Tsunoda; Chiaki Ishihara; Kazuyoshi Ikuta



Antibody Blood Tests  


... my positive antibody test suggests I may have celiac disease, how do I find out for sure? If ... For more information contact the University of Chicago Celiac Disease Center at 773.702.7593 or www.CeliacDisease. ...


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.  


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. PMID:23793639

Eisenberg, Susanne W F; Chuchaisangrat, Ruj; Nielen, Mirjam; Koets, Ad P



Ideology, interest-group formation, and protest: the case of the anti-nuclear power movement, the Clamshell Alliance, and the New Left  

Microsoft Academic Search

The thesis analyzes the development of the Clamshell Alliance, the first and most successful anti-nuclear power protest group. The key question the dissertation asks is how did this organization stage such popular and well-attended protests during a period when leftist political activity seemed to have died out, and little mass protest was taking place. The thesis also explores why the



Confirmatory serologic testing for acute toxoplasmosis and rate of induced abortions among women reported to have positive Toxoplasma immunoglobulin M antibody titers  

Microsoft Academic Search

Objective: Results obtained with commercial testing kits for immunoglobulin M Toxoplasma antibodies may be inaccurate or may be inaccurately interpreted, which may influence whether a woman decides to terminate the pregnancy. This study was undertaken to determine whether confirmatory testing at a reference laboratory and communication of the results and an expert interpretation to the patient’s physician would affect the

Oliver Liesenfeld; Jose G. Montoya; Naga J. Tathineni; Meg Davis; Byron W. Brown; Kristin L. Cobb; Julie Parsonnet; Jack S. Remington



Rapid HIV testing using Determine™ HIV 1/2 antibody tests: is there a difference between the visual appearance of true- and false-positive tests?  


HIV point-of-care tests (POCTs) give occasional false positive results, causing unnecessary patient anxiety. We aimed to elicit whether false- and true-positive POCTs differed visually. Seventeen false- and 17 true-positive serum samples were randomized into pairs, comprising one false- and one true-positive sample. Two independent readers identified each POCT as negative or positive and compared line strength between pairs. Six further readers graded line strength, 0-5, from POCT photographs. All true-positive samples were identified positive and 8/17 false-positive samples negative, on repeat testing of stored sera. Eight out of the 9 remaining false-positive tests were described as having weaker pigment uptake than their paired true-positive POCT. Mean grade of line strength was 4.2 in true- and 0.9 in false-positive samples, on photographic evaluation. These results suggest false-positive POCTs may differ visually from true-positive POCTs. If larger studies confirm these findings, we may be able to alleviate anxiety in low risk patients with faintly positive POCTs awaiting their confirmatory laboratory result, where the possibility of a false-positive result could be emphasized. PMID:23033518

Sacks, R; Omodele-Lucien, A; Whitbread, N; Muir, D; Smith, A



DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.  


Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decalysine or (DOTA)5-decalysine to the antibody heavy chain (via Gln295/297) gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177)Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA)-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA)3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA)5-decalysine)]2. The rapid elimination from the blood of chCE7agl-[(DOTA)-decalysine]2 (1.0±0.1% ID/g at 24 h) is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h). This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA)3 versus 11.7±1.4% ID/g (DOTA)5, p<0.005 at 24 h) and lower radioactivity levels in the liver (21.4±3.4 (DOTA)3 versus 5.8±0.7 (DOTA)5, p<0.005 at 24 h). We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA)5-decalysine) to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for radioimmunotherapy and potentially antibody-drug conjugates (ADCs). PMID:23565233

Grünberg, Jürgen; Jeger, Simone; Sarko, Dikran; Dennler, Patrick; Zimmermann, Kurt; Mier, Walter; Schibli, Roger



DOTA-Functionalized Polylysine: A High Number of DOTA Chelates Positively Influences the Biodistribution of Enzymatic Conjugated Anti-Tumor Antibody chCE7agl  

PubMed Central

Site-specific enzymatic reactions with microbial transglutaminase (mTGase) lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N?-N??-N???-tetraacetic acid (DOTA) chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA)1-decalysine, (DOTA)3-decalysine or (DOTA)5-decalysine to the antibody heavy chain (via Gln295/297) gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with 177Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA)-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA)3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA)5-decalysine)]2. The rapid elimination from the blood of chCE7agl-[(DOTA)-decalysine]2 (1.0±0.1% ID/g at 24 h) is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h). This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA)3 versus 11.7±1.4% ID/g (DOTA)5, p<0.005 at 24 h) and lower radioactivity levels in the liver (21.4±3.4 (DOTA)3 versus 5.8±0.7 (DOTA)5, p<0.005 at 24 h). We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA)5-decalysine) to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for radioimmunotherapy and potentially antibody-drug conjugates (ADCs).

Sarko, Dikran; Dennler, Patrick; Zimmermann, Kurt; Mier, Walter; Schibli, Roger



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



Risk of progression from undifferentiated arthritis to rheumatoid arthritis: the effect of the PTPN22 1858T-allele in anti-citrullinated peptide antibody positive patients  

Microsoft Academic Search

Objectives. Anti-citrullinated peptide antibodies (ACPA) and the C1858T missense single-nucleotide polymorphism (SNP) in the PTPN22 gene are both associated with the development of rheumatoid arthritis (RA). We investigated whether the combination of these two biomarkers yielded better test characteristics to predict progression from undifferentiated arthritis (UA) to RA compared with ACPA alone. Methods. A total of 394 individuals with UA

A. L. Feitsma; R. E. M. Toes; A. B. Begovich; A. P. Chokkalingam; R. R. P. de Vries; T. W. J. Huizinga; A. H. M. van der Helm-van Mil



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



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.  


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. PMID:24049108

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; Ueti, Massaro W



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



Arthritis associated with Strongyloides stercoralis infection in HLA B-27-positive African.  


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 cause arthritis. Filariasis was excluded. Microscopy of fresh stool revealed larvae of Strongyloides stercoralis. Symptoms resolved after specific antihelminthic therapy with ivermectin 0.2 mg kg(-1) day(-1) for 2 days and non-steroidal anti-inflammatorials. Reactive arthritis is known to be caused by various bacterial agents. In some individuals, arthritis may be due to helminths, such as S. stercoralis. Patients with strongyloidiasis may respond to non-steroidal anti-inflammatorials but must not undergo treatment with corticosteroids before having received antihelminthic therapy because immunosuppression may result in life-threatening strongyloides hyperinfection syndrome. PMID:16738888

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



The prevalence of immunohistochemically determined oestrogen receptor positivity in primary breast cancer is dependent on the choice of antibody and method of heat-induced epitope retrieval - prognostic implications?  


Abstract Background. Oestrogen receptor (ER) status is important for the choice of systemic treatment of breast cancer patients. However, most data from randomised trials on the effect of adjuvant endocrine therapy according to ER status are based on the cytosol methods. Comparisons with immunohistochemical methods have given similar results. The aim of the present study was to examine whether different ER antibodies and heat-induced epitope retrieval (HIER) methods influence the prevalence of ER-positivity in primary breast cancer. Material and methods. This study is based on patients included in a clinical trial designed to compare the effect of two years of adjuvant tamoxifen versus no adjuvant systemic treatment in premenopausal women. From 1986 to 1991, 564 patients from two study centres in Sweden were enrolled and randomised. Patients were randomised independently of ER status. In the present study, ER status was assessed on tissue microarrays with the three different ER antibody/HIER combinations: 1D5 in citrate pH 6 (n = 390), SP1 in Tris pH 9 (n = 390) and PharmDx in citrate pH 6 (n = 361). Results. At cut-offs of 1% and 10%, respectively, the prevalence of ER-positivity was higher with SP1 (75% and 72%) compared with 1D5 (68% and 66%) and PharmDx (66% and 62%). At these cut-offs, patients in the discordant groups (SP1-positive and 1D5-negative) seem to have a prognosis intermediate between those of the double-positive and double-negative groups. Comparison with the ER status determined by the cytosol-based methods in the discordant group also showed an intermediate pattern. The repeatability was good for all antibodies and cut-offs, with overall agreement ? 93%. Conclusion. The present study shows that the choice of antibody and HIER method influences the prevalence of ER-positivity. We suggest that this be taken into consideration when choosing a cut-off for clinical decision making. PMID:23343224

Grabau, Dorthe Aamand; Bendahl, Pär-Ola; Rydén, Lisa; Stål, Olle; Fernö, Mårten



Clinical correlation of anticentromere antibodies  

Microsoft Academic Search

A retrospective survey of all patients with a positive anticentromere antibody (ACA) determination was undertaken over a 3-years period of time in a university hospital. Forty-five patients were positive for anticentromere antibodies. The analysis of the clinical characteristics and diagnoses of the patients with anticentromere antibodies were correlated and showed a diverse array of symptoms. Only 4.4% had CREST syndrome,

M. Zuber; R. Gotzen; I. Filler



Antineutrophil cytoplasmic antibody (ANCA)-associated autoimmune diseases induced by antithyroid drugs: comparison with idiopathic ANCA vasculitides.  


Clinical and serological profiles of idiopathic and drug-induced autoimmune diseases can be very similar. We compared data from idiopathic and antithyroid drug (ATD)-induced antineutrophil cytoplasmic antibody (ANCA)-positive patients. From 1993 to 2003, 2474 patients were tested for ANCA in the Laboratory for Allergy and Clinical Immunology in Belgrade. Out of 2474 patients, 72 (2.9%) were anti-proteinase 3 (PR3)- or anti-myeloperoxidase (MPO)-positive and their clinical and serological data were analyzed. The first group consisted of ANCA-associated idiopathic systemic vasculitis (ISV) diagnosed in 56/72 patients: 29 Wegener's granulomatosis (WG), 23 microscopic polyangiitis (MPA) and four Churg-Strauss syndrome. The second group consisted of 16/72 patients who became ANCA-positive during ATD therapy (12 receiving propylthiouracil and four receiving methimazole). We determined ANCA and antinuclear (ANA) antibodies by indirect immunofluorescence; PR3-ANCA, MPO-ANCA, anticardiolipin (aCL) and antihistone antibodies (AHA) by ELISA; and cryoglobulins by precipitation. Complement components C3 and C4, alpha-1 antitrypsin (alpha1 AT) and C reactive protein (CR-P) were measured by nephelometry. Renal lesions were present in 3/16 (18.8%) ATD-treated patients and in 42/56 (75%) ISV patients (p <0.001). Skin lesions occurred in 10/16 (62.5%) ATD-treated patients and 14/56 (25%) ISV patients (p <0.01). ATD-treated patients more frequently had MPO-ANCA, ANA, AHA, aCL, cryoglobulins and low C4 (p <0.01). ISV patients more frequently had low alpha1 AT (p = 0.059) and high CR-P (p <0.001). Of 16 ATD-treated patients, four had drug-induced ANCA vasculitis (three MPA and one WG), while 12 had lupus-like disease (LLD). Of 56 ISV patients, 13 died and eight developed terminal renal failure (TRF). There was no lethality in the ATD-treated group, but 1/16 with methimazole-induced MPA developed pulmonary-renal syndrome with progression to TRF. ANCA-positive ISV had a more severe course in comparison with ATD-induced ANCA-positive diseases. Clinically and serologically ANCA-positive ATD-treated patients can be divided into two groups: the first consisting of patients with drug-induced WG or MPA which resemble ISV and the second consisting of patients with LLD. Different serological profiles could help in the differential diagnosis and adequate therapeutic approach to ANCA-positive ATD-treated patients with symptoms of systemic disease. PMID:16207324

Bonaci-Nikolic, Branka; Nikolic, Milos M; Andrejevic, Sladjana; Zoric, Svetlana; Bukilica, Mirjana



Serum autoantibodies positivity prevalence in patients with chronic HCV and impact on pegylated interferon and ribavirin treatment response.  


BACKGROUND & AIMS: Prevalence of serum autoantibodies in chronic hepatitis C (HCV) patients is higher than that in the general population. Interferon may induce autoimmune manifestations in patients treated with peg-interferon and ribavirin. Effect of autoantibody seropositivity and treatment response are limited and controversial. To detect the prevalence of serum autoantibodies in patients with chronic HCV and impact on histopathology and treatment response. METHODS: Retrospective study including 3673 Egyptian chronic HCV naïve patients enrolled in the Egyptian national programme for HCV treatment with pegylated interferon and ribavirin in the years 2007-2010. Antinuclear antibody (ANA) was determined by ELISA considered positive with a titre ?1:40 by indirect immunofluorescence. ANA-positive patients pre treatment workup including serum aminotransferases, thyroid profile and liver biopsy, follow-up during treatment and sustained virological response (SVR) were assessed compared to ANA-negative patients. RESULTS: Serum ANA was positive in 1.6% of the studied patients. There were no statistically significant differences concerning the demographic, biochemical and histopathological data in ANA positive and negative patients. SVR was comparable between ANA-positive and ANA-negative patients (67.8% and 61.3% respectively). Follow-up treatment; ANA-positive patients' did not experience statistically significant haematological complications, flare-up of serum transaminases, thyroid dysfunction. No systemic autoimmune disorders developed during follow-up. CONCLUSIONS: ANA positivity is not a factor in chronic HCV disease progression and does not affect the treatment response. Pegylated interferon and ribavirin therapy is safe and effective in autoantibodies-positive chronic HCV patients with no need for further follow-up or worry during the treatment in absence of systemic autoimmune disorders. PMID:23763380

Khairy, Marwa; El-Raziky, Maissa; El-Akel, Wafaa; Abdelbary, Mohamed S; Khatab, Hany; El-Kholy, Badawy; Esmat, Gamal; Mabrouk, Mahassen



DNA mobility shift assay as a tool for the detection of anti-dsDNA antibodies in sera from discoid lupus erythematosus patients.  


Discoid lupus erythematosus (DLE) is a form of local inflammatory autoimmune disease limited to the skin, involving essentially the face, scalp and ear. DLE occurs in genetically predisposed individuals, sunlight being an identified trigger. Diagnosis is made by clinical examination and histopathology; laboratory tests occasionally performed include anti-nuclear antibodies titers and presence of circulating antibodies against dsDNA. DLE patients have about a 10% chance of developing systemic lupus erythematosus (SLE), a systemic inflammatory autoimmune disease affecting a range of internal organs. Although elevated titers of anti-dsDNA antibodies is an earmark for lupus disease, they are detected in only 20-55% of DLE patients by routine laboratory tests such as enzyme-linked immunosorbent assay (ELISA). In this research, we applied an electrophoretic mobility shift assay (EMSA) in parallel with an ELISA for the detection of circulating anti-dsDNA in DLE patients. The assays were conducted on sera as well as on the immunoglobulin G fraction from sera of 24 DLE patients and of 24 healthy individuals. The EMSA was positive for all DLE patients while the ELISA was positive for only 36% of them; both assays were negative for the healthy individuals. EMSA conducted on the sera of 15 patients with lichen planus was negative in all cases. Results suggest that the EMSA is more sensitive than the routine tests used for the detection of anti-dsDNA in DLE, thus helping to improve early detection of the disease and, by extension, to better evaluate the factors triggering the disease. PMID:22486312

Keyhani, Jacqueline; Ahadi, Mashallah; Keyhani, Ezzatollah; Naraghi, Zahra; Shamohammadi, Safar



Thyroid Antibodies  


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Anti-cartilage antibody.  


Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change. PMID:389957

Greenbury, C L; Skingle, J



Anti-cartilage antibody.  

PubMed Central

Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change. Images Fig. 1

Greenbury, C L; Skingle, J



Prolonged infections associated with antineutrophil cytoplasmic antibodies specific to proteinase 3 and myeloperoxidase: diagnostic and therapeutic challenge.  


Chronic infections may mimic antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV). We investigated which markers may help in the diagnosis and the prognosis of infections associated with proteinase 3 (PR3) and myeloperoxidase (MPO)-ANCA. In this study (1993-2008)--with an average follow-up of 5.1 years--we compared 66 AAV patients with 17 PR3 and/or MPO-ANCA-positive patients with protracted bacterial (11/17) or viral (6/17) infections. Seven of 17 patients had subacute bacterial endocarditis (SBE), while six of 17 patients had various autoimmune manifestations of chronic hepatitis C virus (HCV) infection. We determined ANCA, antinuclear antibodies, anti-PR3, anti-MPO, anticardiolipin (aCL), antibeta 2 glycoprotein I (beta2-GP I), cryoglobulins, C3, and C4. Patients with infections were younger than AAV patients (p < 0.01). There was no difference in frequency of renal and skin lesions. AAV patients more frequently had pulmonary and nervous system manifestations (p < 0.01). Patients with infections more frequently had dual ANCA (high PR3, low MPO), aCL, anti-beta2-GP I, cryoglobulins, and hypocomplementemia (p < 0.001). Immunosuppressive therapy (IST) was used in five 17 patients who had persistently high ANCA, cryoglobulinemia, and hypocomplementemia. There was no difference in frequency of lethality and renal failure in the two study groups. In patients who are PR3- and/or MPO-ANCA positive, SBE and HCV infection should be excluded. Although similar in renal and skin manifestations in comparison to AAV, only patients with infections developed multiple serological abnormalities. In patients with infections, concomitant presence of ANCA, cryoglobulins, and hypocomplementemia was associated with severe glomerulonephritis. The serological profile should be repeated after specific antimicrobial or surgical therapy, since some cases might require IST. PMID:20306213

Bonaci-Nikolic, Branka; Andrejevic, Sladjana; Pavlovic, Milorad; Dimcic, Zoran; Ivanovic, Branislava; Nikolic, Milos



Interleukin-17 Expression Positively Correlates with Disease Severity of Lupus Nephritis by Increasing Anti-Double-Stranded DNA Antibody Production in a Lupus Model Induced by Activated Lymphocyte Derived DNA  

PubMed Central

Lupus nephritis is one of the most serious manifestations and one of the strongest predictors of a poor outcome in systemic lupus erythematosus (SLE). Recent evidence implicated a potential role of interlukin-17 (IL-17) in the pathogenesis of lupus nephritis. However, the correlation between IL-17 expression level and the severity of lupus nephritis still remains incompletely understood. In this study, we found that serum IL-17 expression level was associated with the severity of lupus nephritis, which was evaluated by histopathology of kidney sections and urine protein. Of note, we showed that enforced expression of IL-17 using adenovirus construct that expresses IL-17 could enhance the severity of lupus nephritis, while blockade of IL-17 using neutralizing antibody resulted in decreased severity of lupus nephritis. Consistently, we observed an impaired induction of lupus nephritis in IL-17-deficient mice. Further, we revealed that IL-17 expression level was associated with immune complex deposition and complement activation in kidney. Of interest, we found that IL-17 was crucial for increasing anti-double-stranded DNA (dsDNA) antibody production in SLE. Our results suggested that IL-17 expression level positively correlated with the severity of lupus nephritis, at least in part, because of its contribution to anti-dsDNA antibody production. These findings provided a novel mechanism for how IL-17 expression level correlated with disease pathogenesis and suggested that management of IL-17 expression level was a potential and promising approach for treatment of lupus nephritis.

Wen, Zhenke; Xu, Lin; Xu, Wei; Yin, Zhinan; Gao, Xiaoming; Xiong, Sidong



Anti-CD20 monoclonal antibody (rituximab) for therapy of CD20-positive nodular lymphocyte-predominant Hodgkin lymphoma in an 10-year-old girl.  


Biologic treatments including antibody-based therapies are still in early-phase development in Hodgkin lymphoma. The authors present the case of a 10-year-old girl with massive, solid, unilateral cervical, nodular lymphocyte-predominant Hodgkin lymphoma. Chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine [ABVD]) and radiotherapy were given, according to the Italian Association of Pediatric Hematology and Oncology (AIEOP) MH-96 study protocol, but the patient failed to enter complete remission. Soon after, 6 intravenous infusions of the chimeric anti-CD20 monoclonal antibody rituximab 375 mg/m2 were administered, resulting in complete remission. The patients is still in continuous complete remission for 2 years. Novel therapies, such as rituximab, may be useful for children with CD20+ nodular lymphocyte-predominant Hodgkin lymphoma. To the authors' knowledge, this is the first report of CD20+ nodular lymphocyte-predominant Hodgkin lymphoma treated with rituximab in children. Further controlled trials and long-term outcome studies are warranted to define its clinical application and to improve the care of patients. PMID:17065142

Culi?, Srdana; Armanda, Visnja; Kuljis, Dubravka; Kuzmic, Ivana; Pranic-Kragic, Ankica; Jankovic, Stipan



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



The pro-solar, anti-nuclear movement: A philosophical perspective  

Microsoft Academic Search

An analysis is presented of the nontechnical reasons for opposing hard technology, such as nuclear power, and supporting soft technology, such as rooftop solar. The positions taken by various advocates are imbedded in an historical and philosophical perspective. Suggestions are brought forth for improving the level of the debate over the various issues discussed.

Carl G. Adler



Buffer substitution in malaria rapid diagnostic tests causes false-positive results  

PubMed Central

Background Malaria rapid diagnostic tests (RDTs) are kits that generally include 20 to 25 test strips or cassettes, but only a single buffer vial. In field settings, laboratory staff occasionally uses saline, distilled water (liquids for parenteral drugs dilution) or tap water as substitutes for the RDT kit's buffer to compensate for the loss of a diluent bottle. The present study assessed the effect of buffer substitution on the RDT results. Methods Twenty-seven RDT brands were run with EDTA-blood samples of five malaria-free subjects, who were negative for rheumatoid factor and antinuclear antibodies. Saline, distilled water and tap water were used as substitute liquids. RDTs were also run with distilled water, without adding blood. Results were compared to those obtained with the RDT kit's buffer and Plasmodium positive samples. Results Only eight cassettes (in four RDT brands) showed no control line and were considered invalid. Visible test lines occurred for at least one malaria-free sample and one of the substitutes in 20/27 (74%) RDT brands (saline: n = 16; distilled water: n = 17; and tap water: n = 20), and in 15 RDTs which were run with distilled water only. They occurred for all Plasmodium antigens and RDT formats (two-, three- and four-band RDTs). Clearance of the background of the strip was excellent except for saline. The aspects (colour, intensity and crispness) of the control and the false-positive test lines were similar to those obtained with the RDT kits' buffer and Plasmodium positive samples. Conclusion Replacement of the RDT kit's dedicated buffer by saline, distilled water and tap water can cause false-positive test results.



Human germline antibody gene segments encode polyspecific antibodies.  


Structural flexibility in germline gene-encoded antibodies allows promiscuous binding to diverse antigens. The binding affinity and specificity for a particular epitope typically increase as antibody genes acquire somatic mutations in antigen-stimulated B cells. In this work, we investigated whether germline gene-encoded antibodies are optimal for polyspecificity by determining the basis for recognition of diverse antigens by antibodies encoded by three VH gene segments. Panels of somatically mutated antibodies encoded by a common VH gene, but each binding to a different antigen, were computationally redesigned to predict antibodies that could engage multiple antigens at once. The Rosetta multi-state design process predicted antibody sequences for the entire heavy chain variable region, including framework, CDR1, and CDR2 mutations. The predicted sequences matched the germline gene sequences to a remarkable degree, revealing by computational design the residues that are predicted to enable polyspecificity, i.e., binding of many unrelated antigens with a common sequence. The process thereby reverses antibody maturation in silico. In contrast, when designing antibodies to bind a single antigen, a sequence similar to that of the mature antibody sequence was returned, mimicking natural antibody maturation in silico. We demonstrated that the Rosetta computational design algorithm captures important aspects of antibody/antigen recognition. While the hypervariable region CDR3 often mediates much of the specificity of mature antibodies, we identified key positions in the VH gene encoding CDR1, CDR2, and the immunoglobulin framework that are critical contributors for polyspecificity in germline antibodies. Computational design of antibodies capable of binding multiple antigens may allow the rational design of antibodies that retain polyspecificity for diverse epitope binding. PMID:23637590

Willis, Jordan R; Briney, Bryan S; DeLuca, Samuel L; Crowe, James E; Meiler, Jens



Anti-idiotypic antibody against anti-DNA in sera of laboratory personnel exposed to lupus sera or nucleic acids.  

PubMed Central

We tested for anti-DNA, anti-idiotypic, antinuclear, and lymphocytotoxic antibodies in the sera of three groups of normals: volunteers never exposed to lupus sera or nucleic acids (group I), research personnel handling nucleic acids (group II), and laboratory personnel handling lupus sera (group III). There was no significant differences among the groups with respect to levels of either single stranded or double stranded anti-DNA. Group I showed no significant differences in binding to F(ab')2 fragments of lupus anti-DNA, lupus non-anti-DNA or normal IgG. Compared to group I, groups II and III bound significantly higher to anti-DNA F(ab')2 fragments compared to non-anti-DNA F(ab')2 or normal F(ab')2 fragments. Sera from the three groups were negative for antibodies and all but one individual from group III had normal antinuclear antibody titres. These results indicate that sera of normals exposed to lupus sera or to nucleic acids contain an anti-idiotype directed against anti-DNA antibody. The possible role of these anti-idiotypes in regulating the anti-DNA antibody is discussed.

Hatfield, M; Evans, M; Suenaga, R; Hassanein, K M; Abdou, N I



Human lymphocyte subpopulations. Human thymus-lymphoid tissue (HTL) antigen-positive lymphocytes forming rosettes with sheep erythrocytes and HTL antigen-negative lymphocytes interacting with antigen-antibody-complement complexes  

PubMed Central

Human lymphocytes from various lymphoid tissues were studied for the relationship between the existence of HTL (human thymus-lymphoid tissue) antigen, and binding of sheep erythrocytes (E) or sheep erythrocyte–antibody-complement complexes (EA(IgM)C43). E adhered to the majority of thymus lymphocytes and formed rosettes. These lymphocytes were shown to be HTL antigen positive by immunofluorescence performed simultaneously. In the peripheral lymphoid tissues, 10–30% of lymphocytes formed E rosettes and almost all E rosette-forming lymphocytes were HTL antigen positive. Conversely HTL antigen-negative cells did not form E rosettes. In contrast, the cells binding EA(IgM)C43 were always HTL antigen negative. There were very few HTL antigen-positive or rosette-forming lymphocytes either with E or EA(IgM)C43 in bone marrow. From these data we conclude that E-rosette-forming and HTL antigen-positive lymphocytes are of thymus origin and EA(IgM)C43-rosette-forming cells are not thymus-dependent cells. ImagesFig. 1

Yata, J.; Tsukimoto, I.; Tachibana, T.



Postpartum Thyroid Dysfunction in Pregnant Thyroid Peroxidase Antibody-Positive Women Living in an Area with Mild to Moderate Iodine Deficiency: Is Iodine Supplementation Safe?  

Microsoft Academic Search

In moderately iodine-deficient, pregnant, thyroid peroxidase an- tibody (TPO-Ab)-positive women the role of iodine supplementation in the development of postpartum thyroid dysfunction (PPTD) was stud- ied in a placebo-controlled, randomized, double blind trial. Screening for TPO-Ab was performed in early pregnancy in a population of healthy pregnant Danish women with no previous diagnosed thyroid disease (prevalence, 117 of 1284; 9.1%).



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



HLA-C alleles confer risk for anti-citrullinated peptide antibody-positive rheumatoid arthritis independent of HLA-DRB1 alleles.  


Objective. The MHC exerts the greatest contribution to RA susceptibility, where certain HLA-DRB1 alleles confer the greatest risk. Interestingly, there is evidence for more risk factors in the MHC with regions surrounding the HLA class I loci, but whether these antigen-presenting loci could be causal risk variants has not been directly investigated. In this study we investigate the HLA association by direct genotyping of the HLA loci. Methods. Nine hundred and fifty RA patients and 933 healthy controls were genotyped for HLA-A, -B and -C. Eleven single-nucleotide polymorphisms (SNPs) and one insertion/deletion in the MHC were also included. Conditional logistic regression analyses were performed separately in ACPA-positive and -negative RA to identify the strongest susceptibility locus and additional risk loci. Results. In ACPA-positive RA, the most significantly associated locus was HLA-DRB1 (P = 1.58 × 10(-54)), with SE alleles being predisposing. After controlling for HLA-DRB1, the HLA-C locus was found to confer susceptibility (P = 2.32 × 10(-9)), particularly, the HLA-C*03 allele. Also, in ACPA-negative RA, HLA-DRB1 was the most significant locus (P = 7.22 × 10(-9)), but with other risk alleles (particularly DRB1*03). A possible independent involvement of HLA-C was also observed for ACPA-negative RA (P = 0.02). Conclusion. HLA-DRB1 was the major MHC risk locus in both ACPA-positive and ACPA-negative RA, but with allelic risk heterogeneity. Joint analyses of the HLA class I loci together with previously proposed SNP associations pointed at HLA-C as a second susceptibility locus in ACPA-positive RA. PMID:23901134

Nordang, Gry B N; Flåm, Siri T; Maehlen, Marthe T; Kvien, Tore K; Viken, Marthe K; Lie, Benedicte A



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



Antithyroid microsomal antibody  


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 ...


Lymphocytotoxic antibodies produced by H-2 allo-immunisation distinguish between MuLV-positive and -negative substrains of the same H-2 haplotype  

Microsoft Academic Search

In C57BL mice of certain H-2 types, such as B10.A (H-2a), ecotropic leukemia virus has been shown to be transmitted by milk-borne infection. By selecting virus-positive and virus-negative B10.A mothers and foster-nursing the B10 (H-2b) newborn animals, four sub-lines of C57BL\\/10 mice have been obtained-B10.A V+, B10.A V-, B10 V+ and B10 V- (see Fig. 1 and ref. 1). Milk

Pavol Ivanyi; Cornelis J. M. Melief; Peter van Mourik; Arjen Vlug; Paul de Greeve




PubMed Central

Injection of a small bacteriophage ?X 174 into guinea pigs results in an accelerated elimination of phage detectable as early as 24 hours after injection. The immune nature of the accelerated elimination is indicated by its specificity, by the appearance of excess specific serum antibody after phage elimination, and by the prevention of accelerated elimination by 400 r whole body x-irradiation of guinea pigs prior to injection of phage. The early antibody response is considered to be a primary one since an analogous response occurs in newborn guinea pigs, antibody is not detectable in the sera of non-immunized animals, and the second challenge with ?X stimulates a serum antibody response 100-fold greater than that after primary immunization. The early detection of immune elimination appears to be due, in part, to the small amounts of phage employed, since larger doses of phage delay the time of onset of detectable immune elimination. The early rise of serum antibody in the primary and secondary response appears exponential with a similar rate constant of antibody formation. The rate constant is also independent of dose. These findings have led to the suggestion that during this exponential phase, the relative rate of antibody formation at a cellular level may be constant for a given antigen.

Uhr, Jonathan W.; Finkelstein, Martin S.; Baumann, Joyce B.



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



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.



The combination of the antiviral agent cidofovir and anti-EGFR antibody cetuximab exerts an antiproliferative effect on HPV-positive cervical cancer cell lines' in-vitro and in-vivo xenografts.  


Cervical carcinoma remains a leading cause of female mortality worldwide and over 90% of these tumors contain the human papillomavirus (HPV) genome. Cross-talk between the epidermal growth factor receptor and HPV has been reported and is implicated in tumor progression. The combination of the antiviral compound cidofovir (Cd) with the monoclonal antibody antiepidermal growth factor receptor cetuximab (Cx) was evaluated. HPV-positive (HeLa and Me180) and HPV-negative (C33A, H460 and A549) human cancer cell lines were incubated with Cd (1-10 ?g/ml) and/or Cx (10 or 50 ?g/ml). The antitumor effect of the combination was assessed in vitro using a clonogenic survival assay, cell cycle analysis, and phospho-H2AX level. Tumor growth delay was assayed in vivo using xenograft models. A pan-genomic analysis was carried out to identify the genes expressed differentially in untreated HeLa HPV-positive cells versus cells treated by the Cd-Cx combination. The Cd-Cx combination inhibited proliferation in all the cell lines tested. The association of Cd and Cx exerted a synergistic activity on HPV-positive but not on HPV-negative cell lines. The combination delayed tumor growth of HPV-positive tumors in vivo; however, no efficacy was reported on HPV-negative C33A xenografts nor on cell lines treated by single-drug therapy. The combination induced an S-phase arrest associated with an enhanced level of the double-strand break in Me180 and HeLa cell lines. Gene profiling assays showed a significant differential modulation of genes in HeLa cell lines treated with the combination involving the EGR-1 transcription factor. The current data support a synergistic antiproliferative action of the Cd-Cx combination on HPV-related cervical tumors. PMID:23698251

Deberne, Mélanie; Levy, Antonin; Mondini, Michele; Dessen, Philippe; Vivet, Sonia; Supiramaniam, Ajitha; Vozenin, Marie-Catherine; Deutsch, Eric



Antithyroglobulin antibody  


... no antibodies to thyroglobulin are found in your blood. Normal value ranges may vary slightly among different laboratories. Some labs use different measurements or test different samples. Talk to your doctor about the meaning of your specific test results.


Several Regions in the Major Histocompatibility Complex Confer Risk for Anti-CCP-Antibody Positive Rheumatoid Arthritis, Independent of the DRB1 Locus  

PubMed Central

Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001–0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.

Lee, Hye-Soon; Lee, Annette T; Criswell, Lindsey A; Seldin, Michael F; Amos, Christopher I; Carulli, John P; Navarrete, Cristina; Remmers, Elaine F; Kastner, Daniel L; Plenge, Robert M; Li, Wentian; Gregersen, Peter K



Antibody penetration of viable human cells. I. Increased penetration of human lymphocytes by anti-RNP IgG.  

PubMed Central

Antibody penetration of viable cells and interaction with intracellular antigens may have major consequences for immunopathological processes in connective tissue diseases. We have reported previously that antibody can penetrate viable human lymphocytes. To assess further the role of antinuclear antibodies in this process, peripheral blood lymphocytes (PBMC) were incubated with FITC-conjugated IgG fractions from sera containing anti-RNP (anti-RNP IgG), Ro(SS-A), La(SS-B) and dsDNA antibodies and control sera for 24 h. Using crystal violet to quench cell surface staining, intracellular fluorescence of viable lymphocytes was quantified on the flow cytometer. It was noted that anti-RNP IgG entered 46.4 +/- 7.2% of lymphocytes which was significantly higher than anti-Ro(SS-A) (29.9 +/- 4.1%, P less than 0.05), La(SS-B) (22.0 +/- 7.5%, P less than 0.01) IgG and control IgG (28.8 +/- 2.1%, P less than 0.05) and not statistically different from anti-dsDNA IgG (32.6 +/- 14.3%). Inhibition experiments showed that the increased number of cells penetrated by anti-RNP IgG was a specific process. Time-course studies showed that anti-RNP IgG entry into cells was different from pooled control IgG. With anti-RNP IgG, positive-staining lymphocytes gradually increased in number from 12 to 24 h incubation, whilst with pooled control IgG, the peak was reached within 5 min. Dual staining experiments suggested that whereas both anti-RNP IgG and pooled control IgG entered B and NK cells, anti-RNP IgG also entered T cells. Using IgG F(ab')2 and Fc fragments from either anti-RNP IgG or pooled control IgG to compete with their FITC-conjugated counterparts indicated that the entry of anti-RNP IgG into-viable cells appeared to involve both F(ab')2 and Fc fragments, and pooled control IgG depended exclusively on the Fc portion of IgG. Further investigation by incubating anti-RNP IgG with 35S-methionine-labelled monocyte-depleted PBMC (MD-PBMC) suggested that anti-RNP IgG might react with the corresponding antigens either on the cell surface or within the cytoplasm. Images Fig. 6

Ma, J; Chapman, G V; Chen, S L; Melick, G; Penny, R; Breit, S N



Fowl antibody  

PubMed Central

Fowls given one injection of 2,4-dinitrophenyl-bovine ?-globulin (DNP-BGG) intravenously or subcutaneously with complete Freund's adjuvant, or multiple injections intramuscularly, responded neither to the hapten nor to the carrier moieties of the antigen. DNP-BGG injected directly into the spleen gave rise to antibodies that precipitated with native BGG, in 0·9 per cent NaCl only, but not with the conjugated protein. Two subcutaneous injections of DNP-BGG mixed with complete adjuvant produced high levels of anti-DNP antibodies. These precipitated with DNP-ovalbumin only in 4 per cent NaCl; there were no precipitating antibodies to BGG. ImagesFIG. 1-4

Orlans, Eva; Saunders, B. Jill; Rose, M. Elaine



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



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.



[Reactivity of antibodies to collagen types I to IV and antibodies to chondroitin sulfate in the spleen].  


Antibodies to collagen type I and III reacted negatively, antibodies to collagen type IV positively with reticulin, trabeculae and circumferent reticulum of lymphatic sheaths, poorly positively with capsula, strongly positively with subcapsular zone. Antibodies to collagen type II reacted positively with capsula, poorly with subcapsular zone, strongly with sinus wall and poorly with trabeculae. They did not react with circumferent reticulum of periarterial lymphoid sheaths. Antibodies to collagen type II and IV reacted positively with central arteries. Antibodies to chondroitinsulphate C reacted poorly and antibodies to chondroitinsulphate B strongly positively with sinus walls and oval cells spread in the white and red pulpa. Antibodies to chondroitin sulphate A reacted similarly as antibodies to chondroitinsulphate B. PMID:9560890

Galbavý, S; Ruzicková, M; Surmíková, E; Danihel, L; Porubský, J; Papincák, J; Holesa, S; Trnka, J



Antibody-targeted cell fusion.  


Membrane fusion has many potential applications in biotechnology. Here we show that antibody-targeted cell fusion can be achieved by engineering a fusogenic viral membrane glycoprotein complex. Three different single-chain antibodies were displayed at the extracellular C terminus of the measles hemagglutinin (H) protein, and combinations of point mutations were introduced to ablate its ability to trigger fusion through the native viral receptors CD46 and SLAM. When coexpressed with the measles fusion (F) protein, using plasmid cotransfection or bicistronic adenoviral vectors, the retargeted H proteins could mediate antibody-targeted cell fusion of receptor-negative or receptor-positive index cells with receptor-positive target cells. Adenoviral expression vectors mediating human epidermal growth factor receptor (EGFR)-targeted cell fusion were potently cytotoxic against EGFR-positive tumor cell lines and showed superior antitumor potency against EGFR-positive tumor xenografts as compared with control adenoviruses expressing native (untargeted) or CD38-targeted H proteins. PMID:14990955

Nakamura, Takafumi; Peng, Kah-Whye; Vongpunsawad, Sompong; Harvey, Mary; Mizuguchi, Hiroyuki; Hayakawa, Takao; Cattaneo, Roberto; Russell, Stephen J



Inhibition of Specific Binding of Antibody to the Rh0(D) Factor of Red Cells in Antibody Excess  

Microsoft Academic Search

The uptake by red cells of I131-labeled nonagglutinating antibody to the Rh0(D) factor was dependent on the proportion of cells to antibody during sensitization. Inhibition of antibody binding by red cells in the region of antibody excess occurred with Rh0(D) positive red cells that were both papain modified and untreated; the inhibition was independent of the Rh phenotype.

S. P. Masouredis; Mary Edith Dupuy; Margaret Elliot



Monoclonal Antibodies  

Microsoft Academic Search

Over the last decades, progress has been made in diagnostic imaging, surgical techniques, radiotherapy, and chemotherapy for\\u000a the treatment of tumors of the central nervous system. However, the outcome for patients with high-grade gliomas (HGG) has\\u000a remained essentially unchanged. The use of monoclonal antibodies (MAbs), either unarmed or armed, to target and kill HGG cells\\u000a has appeared as a prospective

Abraham Boskovitz; David A. Reardon; Carol J. Wikstrand; Michael R. Zalutsky; Darell D. Bigner


Ideology, interest-group formation, and protest: the case of the anti-nuclear power movement, the Clamshell Alliance, and the New Left  

SciTech Connect

The thesis analyzes the development of the Clamshell Alliance, the first and most successful anti-nuclear power protest group. The key question the dissertation asks is how did this organization stage such popular and well-attended protests during a period when leftist political activity seemed to have died out, and little mass protest was taking place. The thesis also explores why the Clamshell Alliance disintegrated at the same time as the anti-nuclear power movement's cause was gaining public acceptance in the wake of the Three Mile Island power-plant accident. The thesis finds that the principal resources the Clamshell drew upon to solve the problems of organizational formation were the activists, organizations, and ideology of the surviving New Left. The dissertation studies the struggles of the Clamshell Alliance as an example of the recurrent problems of leftist political activism in the U.S. It is concluded that only under special conditions can protest outside of regular political channels be both popular and effective. It is also proved that a larger organizational and ideological legacy of the sixties remains than is generally recongnized. Leftist beliefs continued to have adherents even after the protests stopped. Further, many individuals who came to political maturity after the sixties also were found to hold leftist beliefs. However, the political potential of this group can only be realized when an organization temporarily overcomes the barriers to mass leftist political action by developing an issue and a set of tactics that can appeal to leftists and nonleftists alike. Between such special acts of innovation the Left remains a political undercurrent outside of mainstream politics and without a means of effective influence because of its unwillingness to engage in conventional politics.

Cohen, E.M.



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



Neonatal lupus erythematosus: Discordant disease expression of U 1RNP-positive antibodies in fraternal twins—Is this a subset of neonatal lupus erythematosus or a new distinct syndrome?  

Microsoft Academic Search

Neonatal lupus erythematosus (NLE) is an uncommon disease that is manifested by cutaneous lesions, cardiac conduction defects, or both, that appear in utero or shortly after birth. In approximately 95% of patients, anti-Ro antibody (Ro[SS-A]) has been identified and has become the serologic marker for NLE. Since 1987 there have been four reported cases of Ro- and anti-La antibody (La[SS-B])-negative,

Barry A Solomon; Teresita A Laude; Alan R Shalita



Effect of maternal antibodies and pig age on the antibody response after vaccination against Glässers disease.  


The influence of age and maternal antibodies on the development and duration of postvaccinal antibody response against Glässer's disease were investigated. Pigs born to immune (MDA-positive) and non-immune (MDA-negative) sows were vaccinated with inactivated vaccine. Vaccination was done according to three different protocols: at 1 and 4, at 2 and 5 or at 4 and 7 weeks of age. There were also two control groups for MDA-negative and MDA-positive pigs. The level of Haemophilus parasuis (Hps) specific antibodies were determined using commercial ELISA test. No serological responses were seen in any of the groups after the first vaccination. Maternally derived antibodies (MDA) against Hps were above the positive level until approximately 3 weeks of life in MDA-positive pigs. In those pigs the strongest postvaccinal humoral response was observed in piglets vaccinated at 4 and 7 weeks of age. In the remaining MDA-positive piglets only slight seroconversion was noted but levels of antibodies never exceeded values considered as positive. All MDA-negative pigs produced Hps-specific antibodies after the second vaccination. The results of the present study indicated that MDA may alter the development and duration of active postvaccinal antibody response. Age of pigs at the moment of vaccination was not associated with the significant differences in the magnitude of antibody response, however influenced the kinetics of decline of Hps-specific antibodies. PMID:21584780

Pomorska-Mól, Ma?gorzata; Markowska-Daniel, Iwona; Rachubik, Jaros?aw; Pejsak, Zygmunt



[The optimization of techniques complex of serologic diagnostics of connective tissue systemic diseases].  


The connective tissue systemic diseases originate from pathologic process following with antinuclear antibodies emergence. To detect these antibodies a significant number of diagnostic tests and techniques has been applied. Besides that, there is no conventional algorithm of antinuclear antibodies diagnostic. To detect antinuclear antibodies a two-fold diagnostic algorithm was applied In the capacity of screening techniques the indirect immunofluorescence technique was applied to the cells of line Hep-2 (antinuclear factor) and detection of antibodies to extractable nuclear antigen. The second stage of diagnostic included the detection of content of more specific antinuclear antibodies using the Lineblott method and the double-helical DNA antibodies. The blood serum from 981 patients with suspected connective tissue systemic diseases, 115 patients with systemic lupus erythematous and 57 healthy individuals was analyzed. The levels of antinuclear factor, nuclear antigen antibodies and double-helical DNA antibodies were detected. The antinuclear factor was detected in 84% and 86% of cases, double-helical DNA antibodies in 55% and 39% of cases depending of reagents using in detecting these characteristics. Among healthy individuals, antinuclear factor was detected in 5% (1/20) of blood serum samples in titers less than 1:160. In the group of patients with suspected connective tissue systemic diseases, antinuclear factor was detected in 48% (474/981) of cases and extractable nuclear antigen in 20% (326/981) of cases. The Lineblott test was positive in 33% (326/981) of patients with suspected connective tissue systemic diseases. Among antinuclear factor positive patients nuclear antigen antibodies were detected in 36% (171/474) and the Lineblott test was positive in 63% (298/474) of cases. Among antinuclear factor negative patients but positive under anti-nuclear antigen identification, the Lineblott test was positive in 6% (28/507) of cases. The two-fold algorithm of nuclear antigen testing is an effective technique to be applied in the clinical diagnostic laboratory. The results of effectiveness of this algorithm demonstrated that this method can ensure 33% of cost savings of testing individuals with higher incidence of diseases. PMID:22416425

Lazareva, N M; Lapin, S V; Mazing, A V; Bulgakova, T V; Ilivanova, E P; Maslianski?, A L; Totolian, A A



Antibody isotypes of immune complexes in schistosomiasis mansoni in Sudan.  


From a panel of monoclonal antibodies to Schistosoma mansoni, one that is specific to a shared cercarial and schistosomular antigen, and does not react with other major parasite species including Fasciola hepatica, was selected for use as an antigen-capture layer in a sandwich ELISA for detection of specific circulating immune complexes in the blood of S. mansoni-infected subjects from Sudan. The test, which identifies immune complexes of only a single antibody-bound antigen, is developed using human Ig class- and IgG subclass-specific enzyme (HRP)-antibody conjugates. European blood donor sera and those with rheumatoid factor and/or anti-nuclear antibody are negative in this test. The prevalence and distribution of the different antibody isotypes in antigen-specific complexes was determined in 276 subjects of four infection groups; primary school children, adult irrigation canal cleaners with chronic infections, an equivalent group of Praziquantel cured canal cleaners, and hospital-referred cases with severe hepatosplenic symptoms. The isotype profiles of antibodies in the specific complexes were compared with those in the total serum complexes prepared by polyethylene glycol precipitation. In chronic infections and in children there is a high prevalence of IgG and IgM specific complexes, the IgG being predominantly IgG1, with little or no IgG3 and IgG4. Treated chronic infections show reduced specific complexes in all classes of antibody. Compared with chronic and children's infections, a large proportion of the patients with severe infections have in addition to high IgM, high levels of IgG2, IgG3 and IgG4 specific complexes, a fact which suggests a causal relationship between antibody production in one or more of these subclasses to the circulating antigen and symptoms of hepatosplenic disease. Although all subjects have significant amounts of total serum complexes with IgG, untreated chronic infections have much higher concentrations than other infected groups. This group also has the highest levels and prevalence of IgM and IgE complexes. In treated chronic cases IgG and IgM total complexes are greatly reduced. The significant finding in patients with severe symptoms is the relatively high IgA immune complex level compared with other groups. Taken overall the results suggest that screening of populations in endemic regions for serum immune complexes by specific and non-specific means could offer valuable data on the significance of antibody responses to circulating antigens in different isotypes in relation to pathogenesis.(ABSTRACT TRUNCATED AT 400 WORDS) PMID:3124064

Jassim, A; Catty, D; Hassan, K



Positive, accurate animal identification  

Microsoft Academic Search

Positive, accurate identification of animals and their products would be very helpful in livestock commerce, prevention of theft and fraud and in tracing animals and products to origin. Food safety, animal health, and prevention of epidemics, would be enhanced by combining identification with location. Identification may be by electronic chips, iris or retinal scans, antibody or DNA analysis. A cross

Philip Dziuk



Evaluation of two antibodies against double-stranded DNA assays in discriminating between active and non-active systemic lupus erythematosus: correlation between the cut-off and the specificity.  


This study aimed to evaluate, improve and compare the performances of two anti-double-stranded DNA (dsDNA) detection kits, differing by their affinity, in discriminating between active and non-active systemic lupus erythematosus (SLE). Eighty-two anti-nuclear antibody positive sera (45 patients) were tested by two anti-dsDNA commercial quantitative assays (Fidis™, Farrzyme™). All the patients fulfilled at least four of the revised American College of Rheumatology criteria. SLE disease activity was assessed using a modified SLEDAI to remove anti-dsDNA descriptors. When using the manufacturers' cut-offs, no difference in the frequency of positive results was found with respect to disease activity, with Fidis™. On the contrary, with Farrzyme™, a significantly higher frequency of positive sera was found in active SLE patients. Nonetheless, poor performances were observed for both tests. With thresholds defined by ROC methodology, 212IU/mL for Fidis™ (Se: 83.9%, Sp: 86.3%), and 68.8IU/mL for Farrzyme (Se: 71.0%, Sp: 96.1%), a great improvement of the accuracy of the two methods was observed. Moreover, the better specificity and pLR, obtained after optimization of the Farrzyme™ test, could also be obtained with the Fidis™ assay by using a higher threshold than that obtained after optimization of the test. We concluded that when using manufacturers' cut-offs, the two assays appeared to be of poor clinical usefulness in the determination of disease activity. A great improvement was observed using higher thresholds. Moreover, a good concordance could be observed between the two assays (?=0.764). PMID:22265124

Martin, J; Durant, C; Rimbert, M; Hemont, C; Hamidou, M; Audrain, M



Avidity of onconeural antibodies is of clinical relevance.  


Onconeural antibodies are important in the detection of paraneoplastic neurological syndromes (PNS). The avidity of Hu, Yo, and CRMP5 antibodies from 100 patients was determined by immunoprecipitation (IP), and 13 of the Yo positive sera were also tested by surface plasmon resonance (SPR). There was a significant association between the results from IP and SPR. Yo antibodies had higher avidity than Hu and CRMP5 antibodies, and both high- and low-avidity antibodies were associated with tumors and PNS. High-avidity Yo antibodies were mainly associated with ovarian cancer, whereas high-avidity Hu and CRMP5 antibodies were mainly associated with small-cell lung cancer. Low-avidity CRMP5 and Yo antibodies were less often detected by a commercial line blot than high-avidity antibodies. The failure to detect low-avidity onconeural antibodies may result in under diagnosis of PNS. PMID:23733227

Totland, Cecilie; Ying, Ming; Haugen, Mette; Mazengia, Kibret; Storstein, Anette; Aarseth, Jan; Martinez, Aurora; Vedeler, Christian



Reagents Data Portal Antibodies

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.


Identification of nuclear spliceosomal antigens targeted by NOD mouse antibodies following sodium iodide intake.  


The non-obese diabetic (NOD) mouse spontaneously develops a range of autoreactive responses including an autoantibody response to nuclear antigens. As elevated dietary iodine has been shown to increase thyroid autoimmune pathology in NOD mice, the effect of sodium iodide (NaI) on the development of anti-nuclear antibodies (ANA) was assessed. Interestingly, the NaI symporter is expressed in both thyroid and salivary glands. Elevated dietary iodine was found to increase the percentage of male NOD mice developing autoantibodies. Specifically, the nuclear autoantibodies that develop in NOD mice were shown to target specific spliceosomal components. The target specificity of the autoantibodies was determined using recombinant spliceosomal proteins and shown to include U1A, U170K, U2B'', U2A', as well as the Sm proteins D1, D2, and B. The autoantibody isotypes most consistently represented were IgG2a and IgG2b. PMID:16698665

Thompson, C; Pomeranz Krummel, D A; Jacobsen, H; Nagai, K; Cooke, A



IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis  

Microsoft Academic Search

Only around 80% of patients with generalized myasthenia gravis (MG) have serum antibodies to acetylcholine receptor (AChR; acetylcholine receptor antibody positive myasthenia gravis (AChR-MG)) by the radioimmuno- precipitation assay used worldwide. Antibodies to muscle specific kinase (MuSK; MuSK antibody positive myasthenia gravis (MuSK-MG)) make up a variable proportion of the remaining 20%. The patients with neither AChR nor MuSK antibodies

Maria Isabel Leite; Saiju Jacob; Stuart Viegas; Judy Cossins; Linda Clover; B. Paul Morgan; David Beeson; Nick Willcox; Angela Vincent



No Correlations Between the Development of Specific IgA and IgM Antibodies Against Anti-TNF Blocking Agents, Disease Activity and Adverse Side Reactions in Patients with Rheumatoid Arthritis.  


The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-? agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity. PMID:24115967

Benucci, Maurizio; Saviola, Gianantonio; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Campi, Paolo; Severino, Maurizio; Iorno, Miriam; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola



No Correlations Between the Development of Specific IgA and IgM Antibodies Against Anti-TNF Blocking Agents, Disease Activity and Adverse Side Reactions in Patients with Rheumatoid Arthritis  

PubMed Central

The use of tumour necrosis factor (TNF) antagonists (infliximab [IFN], etanercept [ETN], adalimumab [ADA]) has changed the course of many rheumatic diseases, including rheumatoid arthritis (RA). However, some questions concerning their safety have emerged since their approval because they can trigger immunisation, induce rare type I and III hypersensitivity, and cause acute and delayed reactions. The aim of this study was to evaluate the correlations between hypersensitivity reactions to biological agents, disease activity and the development of class-specific IgA and IgM antibodies against the three anti-TNF agents in patients with RA. This longitudinal observational study involved consecutive outpatients with active RA who started treatment with IFN (n=30), ETN (n=41) or ADA (n=28). Clinical data and systemic and local side effects were collected prospectively at baseline and after six months of anti-TNF treatment. Serum samples were taken at the same time points in order to measure antibodies against the TNF blockers, anti-nuclear (ANA) and anti-dsDNA antibodies. The IgA and IgM antibodies specific to all three anti-TNF-? agents were analysed using ImmunoCaP Phadia- Thermofisher especially developed in collaboration with the laboratory of Immunology and Allergy, San Giovanni di Dio, Florence. The mean age of the 99 patients (86% females) was 54.6±12.4 years, and the median disease duration was 11.2±.3.2 years (range 3-14.3). The three treatment groups were comparable in terms of age, gender, rheumatoid factor and anti-citrullinated peptide (CCP) antibody positivity, and baseline C-reactive protein levels, erythrocyte sedimentation rate, 28-joint disease activity scores, and concomitant medications. Twelve patients treated with INF (40%) had anti-IFN IgM, and two (6%) anti-IFN IgA; 19 patients treated with ADA (68%) had anti-ADA IgM, and four (6%) anti-ADA IgA; and 27 patients treated with ETN (66%) had anti-ETN IgM, and 24 (58%) anti-ETN IgA. There were five systemic reactions in the IFN group, and seven adverse local reactions in both the ADA and the ETN group. There was no correlation between drug-specific IgA and IgM antibodies (p=0.65). There was also no correlation between the antibodies and disease activity after six months of treatment (r=0.189;p=0.32). Our findings show that the development of antibodies against IFN, ADA or ETN of IgA and IgM class are not related to any decrease in efficacy or early discontinuation of anti-TNF treatment in RA patients, nor to systemic and local reactions. Further studies of larger series of RA patients are needed to confirm the relationships between the development of drug-specific antibodies, serum TNF blocker levels, and disease activity.

Benucci, Maurizio; Saviola, Gianantonio; Meacci, Francesca; Manfredi, Mariangela; Infantino, Maria; Campi, Paolo; Severino, Maurizio; Iorno, Miriam; Sarzi-Puttini, Piercarlo; Atzeni, Fabiola



Hydralazine induces Z-DNA conformation in a polynucleotide and elicits anti(Z-DNA) antibodies in treated patients.  

PubMed Central

We studied the effect of hydralazine, an antihypertensive drug with lupus-inducing side effects, on the conformation of poly(dG-m5dC).poly(dG-m5dC) and a plasmid with a 23 bp insert of (dG-dC)n.(dG-dC)n sequences. Using an e.l.i.s.a. with a monoclonal anti-(Z-DNA) antibody Z22, we found that hydralazine provoked the Z-DNA conformation in poly(dG-m5dC).poly(dG-m5dC) at 250-500 microM concentration. The supercoiled form of hydralazine-treated plasmid bound to Z22 in a gel-retardation assay. To examine further whether Z-DNA could act as an inciting agent in anti-nuclear antibody production in patients, we analysed 65 sera from 25 hypertensive patients taking hydralazine and found anti-(Z-DNA) antibodies in 82% of these sera. Sera from age-matched normal controls showed no binding to Z-DNA. Data on sera drawn sequentially from four hypertensive patients showed that antibodies were present after the drug treatment. These data demonstrate the presence of a high incidence of anti-(Z-DNA) antibodies in patients treated with hydralazine and suggest that a possible mechanism for the production of autoantibodies in drug-related lupus might involve the induction and stabilization of Z-DNA by drugs. Images Figure 3

Thomas, T J; Seibold, J R; Adams, L E; Hess, E V



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



Mouse Homocytotropic Antibodies.  

National Technical Information Service (NTIS)

Recent observations on the ability of mouse antiserum to induce homologous passive cutaneous anaphylaxis (PCA) have indicated that mice can also produce a homocytotropic antibody similar in its properties to human reagins. The mouse reagin-like antibody i...

I. Mota D. Wong E. H. Sadun R. W. Gore



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



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



Anti-PDEF antibodies and uses thereof  

US Patent & Trademark Office Database

The present invention relates to an isolated antibody or antigen-binding fragment thereof that specifically binds with high affinity to at least a portion of a segment of human prostate-derived Ets transcription factor (PDEF). The anti-PDEF antibody of the present invention is effective in prognostic and diagnostic assays for detecting PDEF with immunohistochemistry. The present invention also relates to methods of making the anti-PDEF antibody disclosed herein. The present invention further relates to vaccines against cancers associated with positive expression of PDEF, as well as methods for treating those cancers. Vectors, diagnostic kits, and hybridomas are also disclosed.



Detection of antibodies against paramyxoviruses in tortoises.  


Sera from a total of 202 tortoises from six countries and nine species were tested for antibodies against four different reptilian paramyxoviruses (ferlaviruses, ferlaVs) by hemagglutination inhibition (HI) test. The viruses used were a tortoise PMV (tPMV) and three squamatid PMV isolates, each belonging to a different subgroup of ferlaV within the genus Ferlavirus. HI tests revealed that antibodies against ferlaVs occurred regularly in the tested samples (5.5%). One and a half percent of the tested samples have measurable antibody titers against the group A isolate, 3% had antibodies against the group B isolate, and 1% had antibodies against the group C isolate. The significantly highest number of positive reactions was detected against the tortoise isolate (5%). Most of the animals that tested positive for one of the snake isolates also tested positive in HI assays with the tortoise isolate. Of the samples from different origins, the sera from Great Britain showed the highest percentage of positive tested animals (10.3%, n = 39), followed by those from Spain (10%, n = 10), while none of the samples from Madagascar or Italy scored positive. Since in most cases animals from one country came from the same collection, this does not represent the real prevalence of ferlaV in tortoises in these countries but rather indicates that ferlaVs occur in a number of different countries and tortoise species. PMID:23805552

Rösler, Reinhild; Abbas, Maha Diekan; Papp, Tibor; Marschang, Rachel E



Immunochemical characterization of human antibodies to lymphoblastoid interferon.  

PubMed Central

Antibodies produced in recurrent respiratory papillomatosis (RRP) patients treated with lymphoblastoid interferon (lyIFN) may neutralize antiviral activity or may only bind to lyIFN. These antibodies were characterized for immunoglobulin class, IgG subclass, and light chain type by an indirect immunoassay. Serum dilutions were incubated on lyIFN-coated plates and the presence of antibody detected using peroxidase-conjugated goat antibodies to each human immunoglobulin class and light chain isotype, or using MoAbs to each human IgG subclass. Neutralizing activity was measured as the inhibition of lyIFN antiviral activity for Vervet monkey cells challenged with Semliki Forest Virus. Among antibody-positive patients, 12% produced IgM coincident with IgG, and 25% produced IgA coincident with IgG. Thus, antibody responses in patients treated with lyIFN are not exclusively of IgG class. The predominant lyIFN-specific subclasses were IgG1 and IgG3, which occurred in 70% and 83% of patients, respectively. An IgG4 response was detected in two patients who also had antibody of other isotypes; no IgG2 antibody was detected in any patient. Antibodies were not IgG subclass-restricted, a trend which was more pronounced in patients having neutralizing antibody than non-neutralizing antibody. Light chain molecules of lyIFN-specific antibody were of both kappa and lambda isotypes, with kappa chains occurring most frequently. Among patients having non-neutralizing antibodies, monotypic light chains occurred in 65% of the patients, whereas no patient with neutralizing antibody had monotypic light chain antibody. Sera from 599 normal human volunteers were assayed for antibody, and seven were found to be immunoreactive to lyIFN. Only one serum of the seven was positive for neutralizing activity.

Thurmond, L M; Reese, M J



Counterimmunoelectrophoresis, ELISA and immunoblotting detection of anti-Ro/SSA antibodies in subacute cutaneous lupus erythematosus. A comparative study.  


Patients with subacute cutaneous lupus erythematosus (SCLE) have circulating antibodies to Ro/SSA directed to two antigenically distinct ribonucleoproteins of 60 kDa and 52 kDa. Three laboratory tests may be used to detect anti-Ro/SSA antibodies: counterimmunoelectrophoresis (CIE), enzyme-linked immunosorbent assay (ELISA) and immunoblotting (IB). Their relative efficacy and clinical correlations were ascertained. We determined anti-Ro/SSA antibodies with CIE, with two different ELISA methods (ELISA 1 and 2) and with IB in 29 SCLE patients. Anti-52 kDa and -60 kDa Ro/SSA antibodies were also assayed with IB. In addition, we determined antinuclear antibodies with indirect immunofluorescence, anti-Sm, anti-RNP, anti-La/SSB and anti-Ro/SSA antibodies with CIE and ELISA, and anti-nDNA and cardiolipin antibodies using an ELISA method. CIE detected anti-Ro/SSA antibodies in 22 patients while ELISA 1 and 2 did so in 17 and 18 patients, respectively. In five patients, IB revealed a reactivity to 60 kDa polypeptides and in two, a reactivity to 52 kDa polypeptides. Of these seven patients, four had a myocardial infarction. Of these, two reacted to the 52 kDa antigen and two to the 60 kDa antigen. A combination of techniques was often needed to detect all specificities. ELISA proved to be very specific and sensitive. The IB technique detected a group of patients with myocardial infarction. A case-control study is needed to confirm the data of cardiac involvement. PMID:9536232

Parodi, A; Drosera, M; Barbieri, L; Rebora, A



In vitro antibody production.  


This unit describes the antigenic stimulation of in vitro antibody production by B cells and the subsequent measurement of secreted antibodies. A generalized system for inducing in vitro antibody production is presented along with a procedure for quantifying the number of antibody-producing cells by plaque-forming cell (PFC) assays: the Cunningham-Szenberg technique and the Jerne-Nordin technique. The assay can be modified as described to measure all classes of antibodies or to enumerate total immunoglobulin-secreting B cells. A protocol for preparing the resting B cells by Percoll gradient centrifugation is also described. PMID:18265070

Mond, J J; Brunswick, M



[VGKC-complex antibodies].  


Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease). PMID:23568988

Watanabe, Osamu



Positive Position Interlock Concealment Shutter.  

National Technical Information Service (NTIS)

The patent relates to a positive position interlock concealment shutter for preventing the accidential or intentional actuation of a concealed interlock switch in a microwave oven when its door is in the open position. It comprises a moveable metal plate ...

E. W. Robinson A. V. D. Griek R. W. Kisielewski



Positive Psychology  

ERIC Educational Resources Information Center

|Positive psychology is a deliberate correction to the focus of psychology on problems. Positive psychology does not deny the difficulties that people may experience but does suggest that sole attention to disorder leads to an incomplete view of the human condition. Positive psychologists concern themselves with four major topics: (1) positive

Peterson, Christopher



Positive Psychology \\  

Microsoft Academic Search

Positive psychology is the study of human strength, resilience, and optimal human functioning. The goal of positive psychology is to make people happier by understanding and building positive emotion, gratification and meaning. The constructs of happiness, hope, optimism, well-being, resilience and flow are examined in how they relate to positive psychology. The \\

Andrew W Fleming



Method for altering antibody light chain interactions  


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)



Prevalence of cattle persistently infected with bovine viral diarrhea virus in 20 dairy herds in two counties in central Michigan and comparison of prevalence of antibody-positive cattle among herds with different infection and vaccination status  

Microsoft Academic Search

All cattle in 20 dairy herds randomly selected from herds participating in the Dairy Herd Im- provement Association program in 2 counties in central Michigan were tested for the presence of bovine viral diarrhea virus (BVDV). Virus-positive animals were retested to ascertain persistent infection with the virus. A total of 5,481 animals were tested for presence of BVDV. In 9

H. Houe; J. C. Baker; R. K. Maes; H. Wuryastuti; R. Wasito; P. L. Ruegg; J. W. Lloyd




PubMed Central

The composition of various isolated antibodies was determined by quantitative analyses for heavy chain subgroups and light chain types. Certain antibodies such as anti-tetanus toxoid and anti-A isoagglutinins were predominantly of the major ?G1-type. However, a high preponderance of molecules of the minor ?G2-subgroup was found for antibodies to dextran, levan, and teichoic acid. These findings explain some unusual features previously noted for anti-dextrans such as weak PCA reactions and lack of Gm antigens. Studies of several isolated antibodies from single heterozygous individuals showed a selective absence of genetic markers in certain antibodies and their presence in others. The "allelic exclusion" principle was clearly evident in the isolated antibodies of two different individuals. Large differences in the ratio of kappa to lambda light chains were observed for the same type of antibody from different individuals. Subfractionation of dextran antibodies by affinity for specific glycosidic linkage or combining site size produced marked changes in the ratios. The isomaltohexaose eluates of the dextran antibodies from two subjects were primarily kappa and the isomaltotriose eluates were predominantly lambda. The one anti-levan antibody studied was uniquely homogeneous, consisting exclusively of ?G2-heavy chains and kappa light chains. By these criteria as well as others, it closely resembled myeloma proteins.

Yount, William J.; Dorner, Marianne M.; Kunkel, Henry G.; Kabat, Elvin A.



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



Have we overestimated the benefit of human(ized) antibodies?  

PubMed Central

The infusion of animal-derived antibodies has been known for some time to trigger the generation of antibodies directed at the foreign protein as well as adverse events including cytokine release syndrome. These immunological phenomena drove the development of humanized and fully human monoclonal antibodies. The ability to generate human(ized) antibodies has been both a blessing and a curse. While incremental gains in the clinical efficacy and safety for some agents have been realized, a positive effect has not been observed for all human(ized) antibodies. Many human(ized) antibodies trigger the development of anti-drug antibody responses and infusion reactions. The current belief that antibodies need to be human(ized) to have enhanced therapeutic utility may slow the development of novel animal-derived monoclonal antibody therapeutics for use in clinical indications. In the case of murine antibodies, greater than 20% induce tolerable/negligible immunogenicity, suggesting that in these cases humanization may not offer significant gains in therapeutic utility. Furthermore, humanization of some murine antibodies may reduce their clinical effectiveness. The available data suggest that the utility of human(ized) antibodies needs to be evaluated on a case-by-case basis, taking a cost-benefit approach, taking both biochemical characteristics and the targeted therapeutic indication into account.

Getts, Meghann T; McCarthy, Derrick P; Chastain, Emily ML; Miller, Stephen D



Antilactoferrin antibodies in autoimmune liver disease  

PubMed Central

Antilactoferrin antibodies have been reported in patients with several autoimmune disorders, including primary biliary cirrhosis, autoimmune hepatitis and autoimmune cholangitis. We investigated the prevalence and the clinical significance of such autoreactivity in patients with autoimmune and viral chronic liver disease. Sera from 39 patients with autoimmune hepatitis, 51 with primary biliary cirrhosis, 17 with autoimmune cholangitis, 24 with primary sclerosing cholangitis and 28 with HCV-related chronic hepatitis were studied. Positivity for antilactoferrin antibodies was evaluated by Western immunoblotting with purified human lactoferrin. Antilactoferrin antibodies were detected more often in autoimmune liver disorders (25% autoimmune hepatitis, 25% primary biliary cirrhosis, 35% autoimmune cholangitis, 29% primary sclerosing cholangitis) than in HCV-related chronic hepatitis (3·5%, P < 0·02 versus all). Positivity for antilactoferrin antibodies was not associated with a particular clinical or biochemical profile of the underlying liver disease. No correlation was observed between antilactoferrin reactivity and perinuclear antineutrophil cytoplasmic antibodies. Antilactoferrin antibodies are present significantly more often in autoimmune than in viral liver disorders, but they cannot be considered the serological marker of a specific autoimmune liver disease.

Muratori, L; Muratori, P; Zauli, D; Grassi, A; Pappas, G; Rodrigo, L; Cassani, F; Lenzi, M; Bianchi, F B




PubMed Central

Rabbits were immunized with a hapten-protein conjugate and sera were collected for 189 days. The antihapten antibodies were purified by affinity chromatography, then the same animal that synthesized the antibody was reinjected with polymerized F(ab')2 fragments of antihapten antibodies. Sera were collected after autoimmunization and tested by an indirect radioimmunoassay technique for reaction with [125I]F(ab')2 fragments of the original antihapten antibody. Results showed that each individual responded to its own F(ab')2 and the antisera were specific for antihapten antibodies of that individual. Quantitative allotype assays established the immunoglobulin nature of the labeled test antigen. Inhibition assays showed that the reaction was specifically inhibitable with hapten. The relationship of this system with other idiotypic systems and the possible autoimmune implications of autoantiidiotypic antibodies are discussed.

Rodkey, L. Scott



Homocytotropic antibody in sheep  

PubMed Central

It has been possible to demonstrate, using the homologous passive cutaneous anaphylaxis (PCA) reaction, the presence of homocytotropic (reagin-like) antibody in the sera of sheep infected with Ostertagia. The presence of antibody was detectable with Evans blue dye, and a radiolabelled 131I technique. The antibody appeared to fulfil the criteria for homocytotropic antibody, and reacted with an allergenic extract (molecular weight 20,000–50,000) of Ostertagia. An in vitro radio-allergo-absorption method using IgG1A (a new sheep immunoglobulin sub-class) failed to detect homocytotropic antibody, although the Fc fragment of goat anti-sheep IgG1A was capable of blocking the PCA reaction, and of producing a reversed-type allergic skin reaction. This homocytotropic antibody is probably associated with the `self-cure' reaction in Ostertagia infection. ImagesFIG. 1

Hogarth-Scott, R. S.



Antibody therapeutics in cancer.  


In a relatively short period of time, monoclonal antibodies have entered the mainstream of cancer therapy. Their first use was as antagonists of oncogenic receptor tyrosine kinases, but today monoclonal antibodies have emerged as long-sought vehicles for the targeted delivery of potent chemotherapeutic agents and as powerful tools to manipulate anticancer immune responses. With ever more promising results from the clinic, the future will likely see continued growth in the discovery and development of therapeutic antibodies and their derivatives. PMID:24031011

Sliwkowski, Mark X; Mellman, Ira



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.



Passive West Nile virus antibody transfer from maternal Eastern Screech-Owls (Megascops asio) to progeny  

USGS Publications Warehouse

Transovarial antibody transfer in owls has not been demonstrated for West Nile virus (WNV). We sampled chicks from captive adult WNV-antibody-positive Eastern Screech-Owls (Megascops asio) to evaluate the prevalence of transovarial maternal antibody transfer, as well as titers and duration of maternal antibodies. Twenty-four owlets aged 1 to 27 days old circulated detectable antibodies with neutralizing antibody titers ranging from 20 to 1600 (median 1:40). Demonstrating that WNV antibodies are passively transferred transovarially is important for accurate interpretation of serologic data from young birds.

Hahn, D.C.; Nemeth, N.M.; Edwards, E.; Bright, P.R,.; Komar, N.



RSV antibody test  


Respiratory syncytial virus antibody test; RSV serology ... Breese HC. Respiratory syncytial virus. In: Mandell GL, Bennett JE, Dolin R, eds. Mandel, Douglas, and Bennett's Principles and Practice of ...


Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA).  


In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (-) sera (P < 0.01). Patients with IF(+) PR3(-)MPO(-) sera showed the most varied reactivity to the minor antigens. Among the IF(+) groups, the IF(+) PR3(+)/MPO(-) sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes. PMID:17614969

Talor, M V; Stone, J H; Stebbing, J; Barin, J; Rose, N R; Burek, C L



Antibodies to selected minor target antigens in patients with anti-neutrophil cytoplasmic antibodies (ANCA)  

PubMed Central

In patients with anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis, indirect immunofluorescence (IF) distinguishes between cytoplasmic (C-ANCA) and perinuclear (P-ANCA) neutrophil staining patterns. In patients with primary systemic vasculitis such as Wegener's granulomatosis, microscopic polyangiitis and Churg–Strauss syndrome, these IF staining patterns correspond broadly with antibodies to the two major antigens: the C-ANCA pattern is associated generally with antibodies to serine protease 3 (PR3) and the P-ANCA pattern with antibodies to myeloperoxidase (MPO). However, some sera positive for ANCA by IF are negative for anti-PR3 and anti-MPO antibodies, suggesting the presence of antibodies to minor antigens of PMN granules. We tested sera from a previously well-defined clinical cohort of patients for antibodies to four possible minor antigens: bactericidal permeability increasing protein, elastase, cathepsin G and lactoferrin. IF-positive (+) sera had significantly higher antibody frequencies to the minor antigens than did the IF-negative (?) sera (P < 0·01). Patients with IF? PR3?MPO? sera showed the most varied reactivity to the minor antigens. Among the IF? groups, the IF? PR3?/MPO? sera showed the lowest reactivity to the minor antigens. Patients with well-defined ANCA specificities, e.g. the PR3-ANCA response associated with Wegener's granulomatosis, are less likely than are other patient subsets to have antibodies to minor antigen targets. Autoantibodies to these minor antigens contribute to the overall pattern of ANCA identified by IF and help to explain why the correlation between IF and enzyme immunoassays show discrepancies. While the pathophysiological significance of antibodies to minor target antigens needs further evaluation, they may be markers of inflammation associated with disease processes.

Talor, M V; Stone, J H; Stebbing, J; Barin, J; Rose, N R; Burek, C L



Antibodies to citrullinated peptides in tuberculosis.  


Rheumatoid arthritis (RA) is an autoimmune disease characterized by symmetric polyarthritis, rheumatoid factor (RF) positivity, and bone erosions. Recently, research has been conducted on anti-citrullinated peptide antibodies (ACPAs) to which there are greater sensitivity and specificity than RF. However, these antibodies have also been described in infectious diseases, particularly tuberculosis (TB), placing the high specificity of the test in doubt. The aim of this research was to study the prevalence of ACPAs in TB, RA, and healthy controls. Patients with bacteriologically confirmed pulmonary tuberculosis, RA (ACR criteria), in addition to healthy controls were included. ACPAs were researched by: anti-cyclic citrullinated peptide (CCP), anti-modified citrullinated vimentin (MCV), and RF by ELISA. The study was conducted in 50 TB patients, 50 with RA, and 20 controls. Anti-CCP antibodies were found in 39 (78 %) of the RA patients (median titer, 128 U), whereas anti-MCV antibodies were found in 25 (50 %). Of the patients with TB, two (4 %) had positivity for anti-CCP and anti-MCV and no patient in the control group tested positive for these antibodies. Sensitivity of anti-CCP for RA was 78 % (confidence interval (CI), 63 to 88 %) and specificity was 97 % (CI, 89 to 99 %) while the sensitivity of anti-MCV was 50 % (CI, 35-64 %) and specificity was 97 % (CI, 89 to 99 %). RF was positive in 40 samples (80 %) of RA, in 30 (60 %) of TB, and in 1 (5 %) of the controls. Our findings showed high sensitivity of anti-CCP and high specificity of both anti-CCP and anti-MCV antibodies for RA, even in a population with high incidence of tuberculosis. The higher frequency of positivity of ACPA in TB observed in previous studies may be attributed to methodological factors. PMID:23344687

Lima, I; Oliveira, R C; Atta, A; Marchi, S; Barbosa, L; Reis, E; Reis, M G; Santiago, M B



Recombinant antibodies to histone post-translational modifications.  


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



Benefit of early treatment in inflammatory polyarthritis patients with anti-cyclic citrullinated peptide antibodies versus those without antibodies  

PubMed Central

Objective To compare the clinical utility of anti–cyclic citrullinated peptide (anti-CCP) antibodies and rheumatoid factor (RF) testing in predicting both functional outcome and response to treatment in early inflammatory polyarthritis (IP) patients. Methods A total of 916 IP subjects from a primary care incidence registry (1990–1994) had anti-CCP antibody and RF status determined at baseline. Mean change in Health Assessment Questionnaire (HAQ) score between baseline and 5 years was compared by antibody status. The effect of treatment with disease-modifying antirheumatic drugs and/or steroids over 5 years, early (<6 months of symptom onset) versus late initiation, and duration of treatment were also compared by anti-CCP antibody status. The analysis was adjusted for treatment decisions and censoring over the followup, using marginal structural models. Results Anti-CCP antibody–positive patients (n = 268) had more severe disease both at presentation and 5 years of followup, and this was independent of RF. On adjustment, anti-CCP antibody–negative patients treated early experienced a significant improvement in functional disability compared with anti-CCP antibody–negative patients who were never treated (?0.31; 95% confidence interval [95% CI] ?0.53, ?0.08), and experienced additional benefit for each additional month of early treatment. Anti-CCP antibody–positive patients treated early did not have a significant improvement in HAQ score compared with those not treated (?0.14; 95% CI ?0.52, 0.24). Conclusion In this first observational study to examine the influence of anti-CCP antibody status on treatment response, anti-CCP antibody–positive IP patients showed less benefit from treatment, particularly early treatment, than anti-CCP antibody–negative patients. This provides support for the inclusion of anti-CCP antibodies as well as RF in the classification criteria for rheumatoid arthritis and for stratification by anti-CCP antibody status in clinical trials.

Farragher, Tracey M; Lunt, Mark; Plant, Darren; Bunn, Diane K; Barton, Anne; Symmons, Deborah P M



Anti-protamine-heparin antibodies: incidence, clinical relevance, and pathogenesis.  


Protamine, which is routinely used after cardiac surgery to reverse the anticoagulant effects of heparin, is known to be immunogenic. Observing patients with an otherwise unexplained rapid decrease in platelet count directly after protamine administration, we determined the incidence and clinical relevance of protamine-reactive antibodies in patients undergoing cardiac-surgery. In vitro, these antibodies activated washed platelets in a Fc?RIIa-dependent fashion. Using a nonobese diabetic/severe combined immunodeficiency mouse model, those antibodies induced thrombocytopenia only when protamine and heparin were present but not with protamine alone. Of 591 patients undergoing cardiopulmonary bypass surgery, 57 (9.6%) tested positive for anti-protamine-heparin antibodies at baseline and 154 (26.6%) tested positive at day 10. Diabetes was identified as a risk factor for the development of anti-protamine-heparin antibodies. In the majority of the patients, these antibodies were transient and titers decreased substantially after 4 months (P < .001). Seven patients had platelet-activating, anti-protamine-heparin antibodies at baseline and showed a greater and more prolonged decline in platelet counts compared with antibody-negative patients (P = .003). In addition, 2 of those patients experienced early arterial thromboembolic complications vs 9 of 584 control patients (multivariate analysis: odds ratio, 21.58; 95% confidence interval, 2.90-160.89; P = .003). Platelet-activating anti-protamine-heparin antibodies show several similarities with anti-platelet factor 4-heparin antibodies and are a potential risk factor for early postoperative thrombosis. PMID:23325832

Bakchoul, Tamam; Zöllner, Heike; Amiral, Jean; Panzer, Simon; Selleng, Sixten; Kohlmann, Thomas; Brandt, Sven; Delcea, Mihaela; Warkentin, Theodore E; Sachs, Ulrich J; Greinacher, Andreas



Human\\/mouse chimeric antibodies show low reactivity with human anti-murine antibodies (HAMA)  

Microsoft Academic Search

Human anti-murine antibody (HAMA) response is a serious problem in the repeated infusion of murine monoclonal antibodies (MoAbs). HAMA positive sera were obtained from seven patients with colorectal cancer, pancreas cancer, malignant melanoma or myocardial infarction who had previously received radiolabelled MoAbs. The nature of HAMA was analysed using size exclusion high performance liquid chromatography (HPLC) after incubating with radiolabelled

M Hosono; K Endo; H Sakahara; Y Watanabe; T Saga; T Nakai; C Kawai; A Matsumori; T Yamada; T Watanabe



Anti-idiotype monoclonal antibody elicits broadly neutralizing anti-gp120 antibodies in monkeys.  

PubMed Central

Murine monoclonal antibodies (mAbs) were raised against human, polyclonal, anti-gp120 antibodies (Ab1) and were selected for binding to broadly neutralizing anti-gp120 antibodies in sera positive for human immunodeficiency virus (HIV). One anti-idiotype mAb (Ab2), 3C9, was found to be specific for human anti-gp120 antibodies directed against an epitope around the conserved CD4 attachment site of gp120. The 3C9 reactive human anti-gp120 antibodies (3C9+ Ab) neutralized MN, IIIB, RF, and four primary isolates of HIV type 1 (HIV-1). Cynomolgus monkeys were immunized with 3C9 in adjuvant to test whether this anti-idiotype mAb could induce neutralizing anti-gp120 antibodies. The results show that purified anti-anti-idiotype antibodies (Ab3) from 3C9 immune sera bind to an epitope around the CD4 attachment site of gp120SF and gp120IIIB. Furthermore, purified gp120-specific Ab3 neutralize MN, IIIB, and RF isolates. These results demonstrate that primates immunized with an anti-idiotype mAb produce broadly neutralizing anti-HIV-1 antibodies. Since this anti-idiotype mAb was selected by identifying a clonotypic marker, its biological activity can be explained as the results of clonotypic B-cell stimulation.

Kang, C Y; Nara, P; Chamat, S; Caralli, V; Chen, A; Nguyen, M L; Yoshiyama, H; Morrow, W J; Ho, D D; Kohler, H



Longitudinal Analysis of Severe Acute Respiratory Syndrome (SARS) Coronavirus-Specific Antibody in SARS Patients  

PubMed Central

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.

Chang, Shan-Chwen; Wang, Jann-Tay; Huang, Li-Min; Chen, Yee-Chun; Fang, Chi-Tai; Sheng, Wang-Huei; Wang, Jiun-Ling; Yu, Chong-Jen; Yang, Pan-Chyr



Characterization of anti-endothelial cell antibodies in systemic lupus erythematosus (SLE).  

PubMed Central

IgG anti-endothelial antibodies (AEA), as measured by ELISA or immunoblotting technique could be detected in serum samples of 56 out of 64 patients with SLE (88%) and mainly occurred in monomeric form. AEA were not cell specific, because the binding reactivity was absorbed partially by both fibroblasts and peripheral blood mononuclear cells. No correlation was found between the presence of AEA and anti-nuclear antibodies. Immunoblotting revealed reactivity of AEA against endothelial antigens ranging in size from 15 to 200 kD. AEA titres were significantly higher in patients with joint or skin abnormalities, compared with patients without these abnormalities. A significant correlation was found between nephritis in SLE and the presence of AEA reactivity against endothelial membrane antigens of 38, 41 and 150 kD. These data show that the pattern of AEA reactivity in serum of SLE patients is heterogeneous, and suggest that AEA against a limited number of antigens may be involved in the pathogenesis of nephritis in SLE. Images Fig. 3 Fig. 4

van der Zee, J M; Siegert, C E; de Vreede, T A; Daha, M R; Breedveld, F C



Antibodies as defensive enzymes  

Microsoft Academic Search

Antibodies (Abs) and enzymes are structural and functional relatives. Abs with promiscuous peptidase activity are ubiquitous in healthy humans, evidently derived from germline variable domain immunoglobulin genes encoding the serine protease-like nucleophilic function. Exogenous and endogenous electrophilic antigens can bind the nucleophilic sites covalently, and recent evidence suggests that immunization with such antigens can induce proteolytic antibodies. Previously, Ab catalytic

Sudhir Paul; Yasuhiro Nishiyama; Stephanie Planque; Sangeeta Karle; Hiroaki Taguchi; Carl Hanson; Marc E. Weksler



Therapeutic Recombinant Monoclonal Antibodies  

ERIC Educational Resources Information Center

|During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

Bakhtiar, Ray



Antibodies in Plants  

Technology Transfer Automated Retrieval System (TEKTRAN)

The expression of antibodies in plants has several promising applications that are currently being developed. Plants are being considered for the large scale production of antibodies needed for medical purposes. The benefit of using plants is that they are able to perform post-translational modifi...


Antibodies to pollen exines  

Microsoft Academic Search

A polyclonal antiserum and monoclonal antibodies have been prepared to purified pollen exines of Calocedrus decurrens Florin. The location of the antigen is in the exine, as shown by light-and electron-microscopic immunocytochemistry. The greatest reduction in antibody binding follows treatment of the exine with chemicals known to alter sporopollenin. These results provide evidence that sporopollenin is antigenic. Exines of ten

D. Southworth; M. B. Singh; T. Hough; I. J. Smart; P. Taylor; R. B. Knox



Antibodies to Mycobacterium paratuberculosis in patients with Crohn's disease  

Microsoft Academic Search

IgG antibodies againstMycobacterium paratuberculosis protoplasmic antigen were looked for by an enzyme immunosorbent assay in patients with Crohn's disease, Ulcerative colitis, active pulmonary tuberculosis, past pulmonary tuberculosis, and in healthy controls. Serum reactivity for these antibodies was not correlated to PPD skin test positivity without history of mycobacterial disease. A cutoff based on the mean absorbance value of a pool

F. Brunello; A. Pera; S. Martini; L. Marino; M. Astegiano; C. Barletti; P. Gastaldi; G. Verme; G. Emanuelli



Familial autoimmune myasthenia gravis with different pathogenetic antibodies.  

PubMed Central

Two cases of familial myasthenia gravis are reported. One patient is a typical case of autoimmune myasthenia with positive anti acetylcholine receptor antibodies, while in the second patient the impairment of neuromuscular transmission is likely to be due to antibodies directed against determinants other than the acetylcholine receptors.

Provenzano, C; Arancio, O; Evoli, A; Rocca, B; Bartoccioni, E; de Grandis, D; Tonali, P



Position Effects  

Microsoft Academic Search

Position effects describe the observed alteration in protein-coding gene expression that may accompany a change in genomic\\u000a position of a given gene. A position effect may result from chromosomal translocation or other genomic rearrangements. Recent\\u000a advances in chromatin studies in several different species including yeast, Drosophila, and mouse have contributed significantly\\u000a to better understanding of human diseases resulting from abnormal

Pawel Stankiewicz


Antibodies for biodefense.  


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. PMID:22123065

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



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



Ebola Virus Antibodies in Fruit Bats, Bangladesh  

PubMed Central

To determine geographic range for Ebola virus, we tested 276 bats in Bangladesh. Five (3.5%) bats were positive for antibodies against Ebola Zaire and Reston viruses; no virus was detected by PCR. These bats might be a reservoir for Ebola or Ebola-like viruses, and extend the range of filoviruses to mainland Asia.

Islam, Ariful; Yu, Meng; Anthony, Simon J.; Epstein, Jonathan H.; Khan, Shahneaz Ali; Khan, Salah Uddin; Crameri, Gary; Wang, Lin-Fa; Lipkin, W. Ian; Luby, Stephen P.; Daszak, Peter



Positive Psychotherapy  

ERIC Educational Resources Information Center

Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.



Positive Psychotherapy  

ERIC Educational Resources Information Center

|Positive psychotherapy (PPT) contrasts with standard interventions for depression by increasing positive emotion, engagement, and meaning rather than directly targeting depressive symptoms. The authors have tested the effects of these interventions in a variety of settings. In informal student and clinical settings, people not uncommonly reported…

Seligman, Martin E. P.; Rashid, Tayyab; Parks, Acacia C.



[Study of the anti Borrelia burgdorferi antibody of hunters in Hokkaido].  


We examined the sera of 587 hunters in Hokkaido (Japan's northernmost island) for the antibody to Borrelia burgdorferi (B. burgdorferi) by enzyme immunoassay, clarified the conditions related to antibody positivity in these subjects according to region, and studied the effects of factors such as age and lifestyle on the antibody titer. In contrast with an anti-B. burgdorferi antibody positive rate of 7.1% in control sera, that in the hunters' sera was 16.0%. Among those positive for the anti-B. burgdorferi antibody, the antibody positive rate in sera excluding those testing positive in the serological test for syphilis was 5.5% in the controls, and 15.4% in the hunters, the latter rate being significantly higher (p less than 0.05). In both hunters and control groups, the antibody-positive rate tended to be higher in older subjects, but the antibody titer showed no correlation with their age, or the duration of their hunting experience. Examination of the hunters' occupations revealed a tendency toward high titers in those engaged in dairy farming. The antibody positivity of those who went gathering edible wild plants was significantly higher than those did not (p less than 0.05). These observations suggested that the high antibody-positive rate in hunters may have been due largely to the effect of activities other than hunting as sources of infection by Borrelia. PMID:1402062

Kubo, N; Arashima, Y; Kawabata, M; Kawano, K; Nakao, M; Miyamoto, K



Monoclonal antibody to chicken oviduct progesterone receptor.  

PubMed Central

Antibodies to molybdate-stabilized chicken oviduct progesterone receptor were raised in a Wistar rat and detected by interaction with homogeneous radioiodinated progesterone receptor. Spleen cells of this rat were then fused with mouse Sp2/0-Ag14 myeloma cells and the antibodies produced by the hybrid cells were detected by double immunoprecipitation using the 125I-labeled receptor. Cells of one of the positive cultures were then cloned by limiting dilution and one hybridoma cell line was studied. The monoclonal antibody produced was an IgG2b, and it reacted with the molybdate-stabilized "8-9S" form of the chicken oviduct progesterone receptor, labeled with either [3H]progesterone or [3H]ORG 2058 (a high-affinity synthetic progestin). Kd for the 8-9S progesterone receptor was approximately equal to 1 nM. Progesterone receptor-monoclonal antibody complexes were labeled with radioactive progesterone, suggesting that antibody does not prevent hormone binding. By using a [35S]methionine-labeled antibody, we were able to detect the progesterone receptor independently of its characteristic function of binding radioactive hormone. No crossreaction with human progesterone receptor was detected.

Radanyi, C; Joab, I; Renoir, J M; Richard-Foy, H; Baulieu, E E



Development of connective tissue disease in patients presenting with Raynaud's phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting  

Microsoft Academic Search

Eighty five patients referred because of Raynaud's phenomenon (RP) were followed up for six years. Every two years they were screened for signs and symptoms of connective tissue disease (CTD) according to a protocol, and serum was stored. Initially, 30 patients had primary RP, 16 had one symptom of CTD ('possible CTD'), 18 had two or more symptoms ('probable CTD'),

C G Kallenberg; A A Wouda; M H Hoet; W J van Venrooij



Infectious antibodies in systemic lupus erythematosus patients.  


Infections can act as environmental triggers that induce or promote systemic lupus erythematosus (SLE) in genetically predisposed individuals. New technologies, developed recently, enable simultaneous assessment of multiple antibodies. Antibodies to specific infectious agents may shed light into the mechanisms of induction of SLE. The aim of this study was to investigate the prevalence of seropositivity and the titers of antibodies to bacterial, viral, and parasitic agents in SLE patients compared with non-autoimmune controls. Sera from 260 individuals (120 SLE patients and 140 controls) were tested by the BioPlex 2200 Multiplexed Immunoassay method (BioRad) for the prevalence and titers of antibodies to eight infectious agents (Epstein-Barr virus: early antigen IgG, nuclear antigen IgG, viral capsid antigen IgG and IgM, heterophile IgM; cytomegalovirus IgG and IgM; Toxoplasma gondii IgG and IgM; rubella IgG and IgM; Treponema pallidum TPr15G, TPr17G, TPr47G; herpes simplex virus type 1 and 2 IgG; hepatitis C virus and hepatitis B core antibodies. Cytomegalovirus IgM and Epstein-Barr virus early antigen IgG (but not other Epstein-Barr virus antigens) were significantly more prevalent in SLE patients than in controls. Conversely, positive titers of hepatitis B core and rubella IgG antibodies were less prevalent in the SLE patients than in controls. Other differences in titer positivity prevalence were not detected between patients and controls. The titers of the cytomegalovirus IgM, Toxoplasma IgG, Epstein-Barr virus early antigen, and viral capsid antigen IgG antibodies were significantly higher in SLE compared with controls. Our data suggest the importance of previous exposure to infectious agents in the induction and the prevention of SLE. PMID:19880558

Berkun, Y; Zandman-Goddard, G; Barzilai, O; Boaz, M; Sherer, Y; Larida, B; Blank, M; Anaya, J-M; Shoenfeld, Y



Monoclonal antibody "gold rush".  


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



Autoradiographic analysis of monoclonal antibody distribution in human colon and breast tumor xenografts  

Microsoft Academic Search

The targeting of monoclonal antibodies to human tumor xenografts in nude mice was investigated by analysis of the cellular distribution of two radioiodinated monoclonal antibodies, B6.2 and B72.3, which recognize different tumor-associated antigens. The time course of distribution of each antibody within Clouser human mammary carcinoma (B6.2 positive, B72.3 negative) and LS174T human colorectal carcinoma (B6.2 positive, B72.3 positive) following

Peter L. Jones; Brian M. Gallagher; Howard Sands



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



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



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



Coxsackievirus B1-based antibody-capture enzyme-linked immunosorbent assay for detection of immunoglobulin G (IgG), IgM, and IgA with broad specificity for enteroviruses.  

PubMed Central

An antibody-capture enzyme-linked immunosorbent assay (ELISA) with coxsackievirus B1 as the antigen was evaluated for detection of immunoglobulin G (IgG), IgM, and IgA antibodies and showed broad specificity for enteroviruses. In total, 116 serum or cerebrospinal fluid samples from 62 patients were tested by ELISA and the complement fixation test (CFT). Additionally, 15 serum samples that contained poliovirus-specific IgM antibody were tested. Serum samples from 200 healthy blood donors were used for standardization of the assays. The sensitivity of the ELISA varied with time of serum sampling, with a relatively low sensitivity when serum was collected within 3 days after the onset of symptoms (23%; 5 of 22) but good sensitivity when serum was collected later (83%; 20 of 24). The sensitivity was better than that of the CFT. The ELISAs were broadly reactive as concluded from typing of virus isolates that were simultaneously obtained. The assay did, furthermore, detect antibody against poliovirus type 3. Sera that contained rheumatoid factor, antinuclear antibody, or cardiolipin antibody (by the Venereal Disease Research Laboratory test) did not react in this ELISA. Nonspecific reactivity did occur, however, in cases of infectious mononucleosis and in Mycoplasma pneumoniae infection. The enterovirus-specific ELISA is found to be simple to perform, more sensitive than the CFT, and far less laborious than the neutralization test.

Swanink, C M; Veenstra, L; Poort, Y A; Kaan, J A; Galama, J M



Amegakaryocytic thrombocytopenia and immune-mediated haemolytic anaemia in a cat  

Microsoft Academic Search

An eleven-month-old female spayed domestic shorthair cat was presented for investigation of pruritic skin lesions and haemorrhage. Haematological evaluation revealed a markedly regenerative anaemia, neutrophilia with left shift, monocytosis, basophilia and severe thrombocytopenia. The direct antiglobulin test and serum antinuclear antibody tests were positive. Serologic and immunofluorescent antibody tests for feline leukaemia virus were negative. Bone marrow cytology revealed a

F. P. Gaschenl; B. Smith Meyer; John W. Harvey



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))



Humanized PAI-1 antibodies  

US Patent & Trademark Office Database

The present application relates to compositions of humanized anti-PAI-1 antibodies and antigen-binding fragments thereof which convert PAI-1 to its latent form. One aspect relates to antibodies having one or more modifications in at least one amino acid residue of at least one of the framework regions of the variable heavy chain, the variable light chain or both. Another aspect relates to antibodies which bind and neutralize PAI-1 by converting PAI-1 to its latent form or increasing proteolytic cleavage. Another aspect relates to the use of humanized antibodies which inhibit or neutralize PAI-1 for the detection, diagnosis or treatment of a disease or condition associated with PAI-1 or a combination thereof.



Anti-sulfotyrosine antibodies  


The invention provides anti-sulfotyrosine specific antibodies capable of detecting and isolating polypeptides that are tyrosine-sulfated. The sulfotyrosine antibodies and antibody fragments of the invention may be used to discriminate between the non-sulfated and sulfated forms of such proteins, using any number of immunological assays, such ELISAs, immunoblots, Western Blots, immunoprecipitations, and the like. Using a phage-display system, single chain antibodies (scFvs) were generated and screened against tyrosine-sulfated synthetic peptide antigens, resulting in the isolation of scFvs that specifically recognize sulfotyrosine-containing peptides and/or demonstrate sulfotyrosine-specific binding in tyrosine sulfated proteins. The VH and VL genes from one such sulfotyrosine-specific scFv were employed to generate a full length, sulfotyrosine-specific immunoglobulin.

Bertozzi, Carolyn R. (Berkeley, CA); Kehoe, John (Saint Davids, PA); Bradbury, Andrew M. (Santa Fe, NM)



Mining human antibody repertoires  

PubMed Central

Human monoclonal antibodies (mAbs) have become drugs of choice for the management of an increasing number of human diseases. Human antibody repertoires provide a rich source for human mAbs. Here we review the characteristics of natural and non-natural human antibody repertoires and their mining with non-combinatorial and combinatorial strategies. In particular, we discuss the selection of human mAbs from naïve, immune, transgenic and synthetic human antibody repertoires using methods based on hybridoma technology, clonal expansion of peripheral B cells, single-cell PCR, phage display, yeast display and mammalian cell display. Our reliance on different strategies is shifting as we gain experience and refine methods to the efficient generation of human mAbs with superior pharmacokinetic and pharmacodynamic properties.



Malaria antibody test development  

Center for Biologics Evaluation and Research (CBER)

... Printable Version. Malaria antibody test development. FDA Workshop on Testing for Malarial Infections in Blood Donors July 12, 2006. ... More results from


Association of ulcerative colitis and red blood cells coated with autoimmune antibody  

Microsoft Academic Search

A young woman with chronic ulcerative colitis, rheumatic heart disease, and mild diabetes mellitus, and who had not had any blood transfusions, developed an autoimmune antibody directed against her own erythrocytes with positive-direct and negative-indirect Coombs' tests. The antibodies disappeared after total colectomy, but were not affected by partial removal of the colon. No circulating anticolon antibodies could be demonstrated

J. A. Balint; W. J. Hammack; T. B. Patton



Determination of acetylcholine receptor antibody in myasthenia gravis: clinical usefulness and pathogenetic implications  

Microsoft Academic Search

Antibodies to cholinergic receptor structures were found in 75% of 76 Finnish and 93% of 175 Swedish patients with myasthenia gravis. The amount of antibodies showed a positive correlation to the severity of the disease, and was reduced during immunosuppressive treatment, and by thymectomy. Thymoma patients had high values. The antibody was also found in the cerebrospinal fluid. Two healthy

A K Lefvert; K Bergström; G Matell; P O Osterman; R Pirskanen



A bioinformatics pipeline to build a knowledge database for in silico antibody engineering  

Microsoft Academic Search

A challenge to antibody engineering is the large number of positions and nature of variation and opposing concerns of introducing unfavorable biochemical properties. While large libraries are quite successful in identifying antibodies with improved binding or activity, still only a fraction of possibilities can be explored and that would require considerable effort. The vast array of natural antibody sequences provides

Shanrong Zhao; Jin Lu



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



Neutralizing antibodies against calcitonin.  


The use of calcitonin (CT) is established as a treatment of Paget's disease of bone and postmenopausal osteoporosis (PMO). Salmon calcitonin (sCT), which differs in 14 of the 32 amino acids from human calcitonin, has found a wider distribution world wide, although antibody formation against sCT has been reported in more than 70% of the patients on continuous sCT treatment. The clinical significance of these antibodies has been discussed controversially, because the occurrence of antibodies is not always associated with the development of secondary resistance. Using an in vitro bioassay, based on the CT-mediated increase of the cyclic AMP (cAMP) production of the human breast cancer cell line T 47 D we could identify a neutralizing activity against sCT in the serum of a subset of patients with formation of antibodies against sCT which was related to the development of secondary resistance. Antibody formation against human calcitonin (hCT) has been reported only once before. Binding and neutralizing antibodies were now observed in 1 of 33 patients with PMO treated with hCT. Due to a low neutralizing activity, clinical sequelae were not to be expected in this patient. The formation of neutralizing antibodies against calcitonin is common after treatment with salmon but a rare phenomenon after treatment with human calcitonin. We recommend monitoring of patients with postmenopausal osteoporosis and Paget's disease of bone on long term treatment with sCT or hCT for neutralizing antibody formation in order to evaluate the therapeutic effect of treatment. PMID:8225203

Grauer, A; Reinel, H H; Ziegler, R; Raue, F



Antibody tumor penetration  

PubMed Central

Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue.

Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane



Anti-CD33-antibodies labelled with the alpha-emitter Bismuth-213 kill CD33-positive acute myeloid leukaemia cells specifically by activation of caspases and break radio- and chemoresistance by inhibition of the anti-apoptotic proteins X-linked inhibitor of apoptosis protein and B-cell lymphoma-extra large.  


AIM: The emerging interest in radioimmunotherapies employing alpha-emitters for cancer treatment like high risk-leukaemia leads to the question of how these radionuclides exhibit their cytotoxicity. To clarify the molecular mechanisms of cell death induction, we investigated the molecular effects of the alpha-emitter Bismuth-213 (Bi-213) bound to a monoclonal anti-CD33-antibody ([Bi-213]anti-CD33) on the cell cycle and on apoptosis induction in sensitive as well as in beta- and gamma-radiation-resistant CD33-positive acute myeloid leukaemia (AML) cells. METHODS: The cytotoxic potential of the radioimmunoconjugate [Bi-213]anti-CD33 was analysed in the CD33-expressing human AML cell line HL-60 and in radiation- and chemoresistant HL-60-derived cell lines. Cell cycle and apoptosis induction analyses were performed via flow cytometry. Activation of apoptosis pathways was determined by immunodetection. RESULTS: [Bi-213]anti-CD33 induced apoptotic cell death in CD33-positive AML cells specifically. Molecular analyses revealed that the intrinsic mitochondrial pathway of apoptosis was activated resulting in caspase-9 activation. In the apoptotic executioner cascade caspase-3 was activated and its substrate poly (ADP-ribose) polymerase (PARP) was cleaved. Notably, [Bi-213]anti-CD33 overcame radio- and chemoresistance by reversing deficient activation of apoptosis pathways in resistant CD33-positive AML cells and by the downregulation of inhibitors of apoptosis B-cell lymphoma-extra large (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) involved in leukaemia resistance. CONCLUSION: [Bi-213]anti-CD33 exhibits its cytotoxic effects specifically in CD33-expressing AML cells via induction of the intrinsic, mitochondrial pathway of apoptosis. The abrogation of chemo- and radioresistances and the reactivation of apoptotic pathways seem to be promising for the treatment of patients with so far untreatable resistant AML and underline the importance of this emerging therapeutic approach of targeted alpha-therapies. PMID:23684782

Friesen, Claudia; Roscher, Mareike; Hormann, Inis; Leib, Oliver; Marx, Sebastian; Moreno, Josue; Miltner, Erich



Genetically engineered antibodies.  


The technology needed to genetically engineer antibodies is evolving rapidly and the potential utility of these novel reagents is being explored with vigor. The process includes cloning of the antibody genes, their in vitro manipulation and mutagenesis, expression in a suitable host/vector system, and, for commercial production, scale-up, purification, and product evaluation. At each step, significant advances have been achieved recently. For example: at first, antibody genes were cloned from genomic libraries by using adjacent DNA probes; techniques for rapid sequencing by primer extension of total mRNA allowed more specific screening with synthesized oligomers; finally, antibody genes can now be created de novo by chemical synthesis. Moreover, such synthesis allows total control over the antibody sequence so that molecules of any configuration can be produced. New reagents created in this way include murine antibodies whose constant regions and variable-region frameworks have been replaced with human sequence to enhance immunocompatibility with patients, to switch immunoglobulin class, or both. PMID:2673580

Moore, G P



Antibody therapy for familial amyloidotic polyneuropathy.  


Although it is believed that altered conformations exposing cryptic regions are intermediary and critical steps in the mechanism of transthyretin (TTR) amyloid formation, no effective therapy targeting this step is available. In this study, to establish the antibody therapy for familial amyloidotic polyneuropathy (FAP), we generated a monoclonal anti-TTR antibody, which specifically reacts with surface epitopes of TTR (MAb ATTR) and evaluated its binding affinity and specificity for TTR amyloid fibrils. MAb ATTR showed specific binding affinity for TTR amyloid fibrils, but not for native form of TTR. Moreover, MAb ATTR indeed showed the high consistency with Congo red positive areas in tissue specimens from FAP ATTR V30M patients, indicating that MAb ATTR showed binding affinity and specificity for TTR amyloid fibrils in vitro and in vivo. MAb ATTR may have a potential to suppress TTR amyloid deposition and become a candidate for the antibody therapy for FAP. PMID:22506915

Su, Yu; Jono, Hirofumi; Torikai, Masaharu; Hosoi, Akihiko; Soejima, Kenji; Guo, Jianying; Tasaki, Masayoshi; Misumi, Yohei; Ueda, Mitsuharu; Shinriki, Satoru; Shono, Makoto; Obayashi, Konen; Nakashima, Toshihiro; Sugawara, Keishin; Ando, Yukio



Specific IgA antibody response in Ross River virus infection  

Microsoft Academic Search

Sera were collected over a period of several years from the onset of initial symptoms from 77 patients with Ross River virus infection. When tested for virus-specific IgA antibodies, using an enzyme-linked immunosorbent assay (ELISA) based on antibody class capture, 245 out of 704 sera were antibody-positive. Although Ross River virus IgA antibodies were present in the serum of all

IWJ Carter; JRE Fraser; MJ Cloonan



Detection of anti- Saccharomyces cerevisiae antibodies in Crohn's disease: is it reliable diagnostic and prognostic marker?  

Microsoft Academic Search

Background. In the past few years, serologic markers have been proposed in inflammatory bowel disease. Anti-Saccharomyces cerevisiae antibodies showed high specificity for Crohn's disease. A prognostic role for serology has also been hypothesised.Aims To evaluate anti-Saccharomyces cerevisiae antibody distribution in an unselected Italian inflammatory bowel disease population. To analyse whether anti-Saccharomyces cerevisiae antibody status (positive\\/negative) and\\/or anti-Saccharomyces cerevisiae antibody titres

R. Sostegni; M. Daperno; E. Ercole; C. Rigazio; F. Bresso; G. Masoero; F. Castellino; C. Zaffino; R. Rocca; G. C. Molinaro; G. Rocca; M. Astegiano; A. Pera



Positively Adolescent!  

ERIC Educational Resources Information Center

|Believes that music teachers should reassess their views toward adolescent behavior in the music classroom by learning to see their behavior in a positive light. Describes teaching strategies that build on four adolescent behaviors: (1) desire for peer acceptance; (2) abundant energy; (3) love of fun; and (4) limited time-managing skills. (CMK)|

Williamson, Sue



Immunoglobulin G antibodies against deamidated-gliadin-peptides outperform anti-endomysium and tissue transglutaminase antibodies in children <2 years age.  


To investigate the usefulness of deamidated-gliadin-peptides-antibodies in the diagnosis of celiac disease, serology was tested in 212 children suspected with celiac disease who had undergone a small-intestinal-biopsy. For deamidated-gliadin-peptides-antibodies, two kits were tested. Positive and negative predictive values for IgA deamidated-gliadin-peptides-antibodies using the Bindazyme-kit were 89% and 74%, while the Quanta-Lite-kit had values of 89% and 85%, respectively. For the IgG subtype using the Bindazyme-kit, these values were 85% and 89%, while they were 85% and 91% for the Quanta-Lite-kit. The positive predictive values for endomysium and tissue-transglutaminase antibodies were disappointing (77% and 87%), although the negative predictive values were better (97% and 96%). When the analysis was restricted to the 41 children aged <2 years, no misclassifications occurred with IgG deamidated-gliadin-peptides-antibodies giving 100% accuracy in both kits. The positive predictive value reached 100% for tissue-transglutaminase antibodies and both kits for IgA deamidated-gliadin-peptides-antibodies, while the negative predictive value was 94% in these assays. Positive and negative predictive values for endomysium antibodies were 96% and 93%, respectively. In conclusion, although deamidated-gliadin-peptides-antibodies do not outperform anti-endomysium antibodies in the total study population, the IgG subtype seems to be the best test in children aged <2 years, reaching 100% accuracy. PMID:22085366

Mubarak, A; Gmelig-Meyling, F H J; Wolters, V M; Ten Kate, F J W; Houwen, R H J



Paranasal sinus disease in HIV antibody positive patients  

Microsoft Academic Search

OBJECTIVE--To investigate the prevalence of radiologically-diagnosed paranasal sinus disease in HIV-1 seropositive patients. SUBJECTS AND SETTING--476 patients admitted to a dedicated inpatient unit for HIV and AIDS at the Middlesex Hospital, London, between September 1988 and February 1992. DESIGN--Retrospective review of patients' case notes and radiological records. RESULTS--30 patients (6.3%) had radiological evidence of paranasal sinus disease. At the time

A Grant; M von Schoenberg; H R Grant; R F Miller



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



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.



Modulation of antibody affinity by a non-contact residue.  


Antibody LB4, produced by a spontaneous variant of the murine anti-digoxin monoclonal antibody 26-10, has an affinity for digoxin two orders of magnitude lower than that of the parent antibody due to replacement of serine with phenylalanine at position 52 of the heavy chain variable region (Schildbach, J.F., Panka, D.J., Parks, D.R., et al., 1991, J. Biol. Chem. 266, 4640-4647). To examine the basis for the decreased affinity, a panel of engineered antibodies with substitutions at position 52 was created, and their affinities for digoxin were measured. The antibody affinities decreased concomitantly with increasing size of the substituted side chains, although the shape of the side chains also influenced affinity. The crystal structure of the 26-10 Fab complexed with digoxin (P.D.J., R.K. Strong, L.C. Sieker, C. Chang, R.L. Campbell, G.A. Petsko, E.H., M.N.M., & S.S., submitted for publication) shows that the serine at heavy chain position 52 is not in contact with hapten, but is adjacent to a tyrosine at heavy chain position 33 that is a contact residue. The mutant antibodies were modeled by applying a conformational search procedure to position side chains, using the 26-10 Fab crystal structure as a starting point. The results suggest that each of the substituted side chains may be accommodated within the antibody without substantial structural rearrangement, and that none of these substituted side chains are able to contact hapten. These modeling results are consistent with the substituents at position 52 having only an indirect influence upon antibody affinity.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8443598

Schillbach, J F; Near, R I; Bruccoleri, R E; Haber, E; Jeffrey, P D; Novotny, J; Sheriff, S; Margolies, M N




PubMed Central

After injection of ovalbumin as a water-in-oil emulsion a pronounced adjuvant effect is demonstrable following the incorporation of tubercle bacillary wax into the oily phase of the mixture. With single doses of antigen (10 mg. ovalbumin) there is a 4- to 5-fold increase in the amount of antibody at the median of 3 week serum levels in animals receiving a small dose of wax (40 µg.). With a 5 mg. dose of wax there is an 8-fold increase in serum antibody levels at the median. A striking feature of the action of wax is the stimulation of a macrophage proliferation locally at the site of injection, and the production of morphological abnormalities in these cells. As judged by staining techniques for antibody content, these locally assembled cells are not active in the formation of antibody. Wax injected in mineral oil results in a remarkable systematized stimulation of the reticulo-endothelial system. The greatly increased serum antibody levels demonstrated after the use of tubercle bacillary wax in antigen mixtures is attributed to a widespread proliferation of plasma cell elements in the lymphatic glands, spleen and liver.

White, Robert G.; Coons, Albert H.; Connolly, Jeanne M.



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



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"…

Lyubomirsky, Sonja




PubMed Central

Neutralizing activity against T2 bacteriophage appeared in cultures of lymph node cells from normal rats in response to their in vitro stimulation with a cell-free filtrate derived from homogenized rat macrophages which had been incubated with T2 bacteriophage. This activity was specifically directed against T2 bacteriophage. It resided in a fraction of the culture fluid which had the salting-out properties of serum globulin. Phage neutralization was inhibited by antibody specific for rat serum gamma globulin. Antibody production against T2 bacteriophage in cultures of lymph node cells from normal animals failed to occur if (a) T2 bacteriophage alone was added, (b) if the incubation period of macrophages and T2 phage was unduly shortened, (c) if the cell-free filtrate was heated at 80–100°C for 15 minutes, (d) if more than an optimal amount of T2 bacteriophage was added to the macrophages. Additional factors which prevented the formation of antibody were the heat inactivation of the lymph node cells or the addition to the culture medium of either streptomycin or ribonuclease. Finally, it was found that macrophages and lymph node cells had to be obtained from animals of one and the same species. All essential findings on the production of antibody to T2 bacteriophage in vitro could be confirmed by substitution of the chick embryo for the tissue culture medium. The results are discussed in terms of a possible mechanism of antibody production in which an RNAse-sensitive substance resulting from the interaction of macrophages and antigen is capable of stimulating antibody synthesis in lymphocytic cells.

Fishman, M.



Occurrence of Epstein-Barr Virus Deoxyribonuclease Enzyme Activity-Neutralizing Antibodies  

Microsoft Academic Search

Summary The occurrence of Epstein-Barr virus (EBV) specific DNase antibodies was measured in the sera of 400 patients. Three hundred sera were positive (>20) for early antigen diffuse component (EA-D) antibodies, as measured by indirect immunofluorescence (IF). One hundred sera were EA-D antibody-negative but had IF IgG titers (>40) to the viral capsid antigen (VCA). Twenty-nine of the anti-EA-D-positive sera,

Bernhard Bardy; Frédéric Morinet; Yvonne Pérol



Positioning apparatus  


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.



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



Human monoclonal antibodies: the residual challenge of antibody immunogenicity.  


One of the major reasons for seeking human monoclonal antibodies has been to eliminate immunogenicity seen with rodent antibodies. Thus far, there has yet been no approach which absolutely abolishes that risk for cell-binding antibodies. In this short article, I draw attention to classical work which shows that monomeric immunoglobulins are intrinsically tolerogenic if they can be prevented from creating aggregates or immune complexes. Based on these classical studies two approaches for active tolerization to therapeutic antibodies are described. PMID:24037833

Waldmann, Herman



Self-assembled antibody multimers through peptide nucleic acid conjugation.  


With the recent clinical success of bispecific antibodies, a strategy to rapidly synthesize and evaluate bispecific or higher order multispecific molecules could facilitate the discovery of new therapeutic agents. Here, we show that unnatural amino acids (UAAs) with orthogonal chemical reactivity can be used to generate site-specific antibody-oligonucleotide conjugates. These constructs can then be self-assembled into multimeric complexes with defined composition, valency, and geometry. With this approach, we generated potent bispecific antibodies that recruit cytotoxic T lymphocytes to Her2 and CD20 positive cancer cells, as well as multimeric antibody fragments with enhanced activity. This strategy should accelerate the synthesis and in vitro characterization of antibody constructs with unique specificities and molecular architectures. PMID:23210862

Kazane, Stephanie A; Axup, Jun Y; Kim, Chan Hyuk; Ciobanu, Mihai; Wold, Erik D; Barluenga, Sofia; Hutchins, Benjamin A; Schultz, Peter G; Winssinger, Nicolas; Smider, Vaughn V



Satellite positioning  

NASA Astrophysics Data System (ADS)

Geodetic positioning programs with the U.S. Navy Transit and GPS satellite systems and satellite laser ranging programs are described. As of 1982 the number of Doppler receivers had increased to over 16,000 units, 1000 with two-frequency geodetic apparatus. The Nova 1 satellite, launched in 1981, was a drag-free satellite, incorporating a single-axis disturbance compensation system (DISCOS) to continuously correct track aberrations due to perturbing forces acting on the satellite. One of the Transit system units, Nova 1 lowered the broadcast ephemeris prediction errors to 5-15 m rms, compared to the 5-70 m rms error for the Oscar satellite. The Navstar GPS system is in full engineering development and will lead to an 18 satellite configuration, with four in view from any point on earth. Global positioning accuracies of 10 m have been found in tests. The Lageos, Starlette, beacon Explorer-C, and Geos-3 satellites have been used in laser ranging experiments to measure polar motions by reflecting laser light from the ground off reflectors on the satellite surfaces. NASA is currently moving a transportable laser station to Easter Island to obtain an accuracy of 10 cm.

Hill, R. W.



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.


Better position  

NASA Astrophysics Data System (ADS)

The U.S. Global Positioning System (GPS) will soon become more accurate for civilian users, improving the quality of navigation and of some types of scientific research. The Clinton Administration announced March 29 that within a decade, the federal government will stop degrading the civilian GPS signal and will allow nonmilitary users access to the same clear signals that U.S. troops rely upon.Designed as dual-use system with primary use by the American military, the GPS is a constellation of 24 satellites that allows soldiers to determine their exact positions (in latitude and longitude) anywhere in the world. While the GPS is operated by the Department of Defense (DoD), scientists and adventurous civilians have been able to purchase small, portable GPS devices. However, the U.S. military has kept to itself a capability known as “selective availability” that provides a much more precise signal than is available to the public. According to the White House, that selected signal will be available to all users within 4-10 years.

Carlowicz, Michael


The activated seven lupus anticoagulant assay detects clinically significant antibodies.  


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



Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women.  


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



An enzyme immunoassay for immunoglobulin M antibodies to Toxoplasma gondii which is not affected by rheumatoid factor or immunoglobulin G antibodies.  

PubMed Central

An enzyme-linked immunosorbent assay (ELISA) for total antibodies to Toxoplasma gondii was modified to measure specific immunoglobulin M (IgM) antibodies. The assay requires three incubation periods totaling 2 h and enzyme-labeled-heavy-chain-specific antibodies to human IgM. The objective read-out in absorbance was normalized to percent of a standardized positive control for interpretations. No difference was observed between the assay results with or without previous absorption of the samples by Staphylococcus aureus protein A to remove most of the IgG antibodies. Addition of serum containing very high levels of IgG antibodies to another containing both IgG and IgM antibodies did not change the IgM assay values for the latter. None of the 22 sera containing high levels of IgM rheumatoid factor (RF) gave positive ELISA IgM results, even though 8 of them also had high levels of IgG toxoplasma antibodies. Mixtures of sera containing high concentrations of RF with sera having high levels of IgG toxoplasma antibodies also failed to show any false-positive reactions in the IgM toxoplasma assay. Thus, this ELISA for T. gondii IgM antibodies was not affected by IgG toxoplasma antibodies and RF.

Lin, T M; Chin-See, M W; Halbert, S P; Joseph, J M



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



Dementia and Antiphospholipid Antibodies  

Microsoft Academic Search

Antiphospholipid antibodies (aPLAb) may cause both focal ischemic and diffuse brain damage and may be associated with dementia. We have examined the relationship of aPLAb to dementia in the elderly. Blood samples were obtained from 87 consecutive patients with dementia (74 ± 11 years old) and 69 controls (78 ± 9 years old), residents of an old age home who

A. Mosek; I. Yust; T. A. Treves; N. Vardinon; A. D. Korczyn; J. Chapman



Monoclonal Antibodies against Pectin  

PubMed Central

Monoclonal antibodies have been produced that recognize a conformation of homopolygalacturonic acid (pectic acid) induced by an optimum concentration of calcium and sodium of about 1 and 150 millinormal, respectively. The epitope recognized is probably part of the dimers of pectin chains associated according to the `egg box' model. Images Figure 2

Liners, Francoise; Letesson, Jean-Jacques; Didembourg, Christian; Van Cutsem, Pierre



Natural antibodies to glycans.  


A wide variety of so-called natural antibodies (nAbs), i.e. immunoglobulins generated by B-1 cells, are directed to glycans. nAbs to glycans can be divided in three groups: 1) conservative nAbs, i.e. practically the same in all healthy donors with respect to their epitope specificity and level in blood; 2) allo-antibodies to blood group antigens; 3) plastic antibodies related to the first or the second group but discussed separately because their level changes considerably during diseases and some temporary conditions, in particular inflammation and pregnancy. Antibodies from the third group proved to be prospective markers of a number of diseases, whereas their unusual level (below or above the norm) is not necessarily the consequence of disease/state. Modern microarrays allowed the determination of the human repertoire, which proved to be unexpectedly broad. It was observed that the content of some nAbs reaches about 0.1% of total immunoglobulins. Immunoglobulins of M class dominate for most nAbs, constituting up to 80-90%. Their affinity (to a monovalent glycan, in KD terms) were found to be within the range 10(-4)-10(-6) M. Antibodies to Gal?1-3GlcNAc (Le(C)), 4-HSO3Gal?1-4GalNAc (4'-O-SuLN), Fuc?1-3GlcNAc, Fuc?1-4GlcNAc, GalNAc?1-3Gal (Adi), Gal?1-4Gal?1-4Glc (P(k)), Gal?1-4Gal?1-4GlcNAc (P1), GlcNAc?-terminated glycans, and hyaluronic acid should be noted among the nAbs revealed and studied during the last decade. At the same time, a kind of "taboo" is observed for a number of glycans: antibodies to Le(X) and Le(Y), and almost all gangliosides have not been observed in healthy persons. Many of the revealed nAbs were directed to constrained inner (core) part of glycan, directly adjoined to lipid of cell membrane or protein. The biological function of these nAbs remains unclear; for anti-core antibodies, a role of surveillance on appearance of aberrant, especially cancer, antigens is supposed. The first data related to oncodiagnostics based on quantitation of anti-glycan nAbs are reported. PMID:24010841

Bovin, N V



From antibodies to sperm to antibodies in transplantation  

Microsoft Academic Search

Objectives. a) To assess the use of “panning” procedures for the detection of antibodies to sperm. b) To develop and use human monoclonal antibodies for the analysis of human transplantation antigens.Methods. “Panning” assays were developed. The procedures and their use in the analysis of mouse monoclonal antibodies to human sperm are described. B-lymphocytes from individuals sensitized by pregnancy, graft rejection,

Richard J. T Hancock



HTLV-I Antibody Testing  

Center for Biologics Evaluation and Research (CBER)

Text VersionPage 1. HTLV-I Antibody Testing (7/6/89) ... FROM: Director, Center of Biologics Evaluation and Research SUBJECT: HTLV-I Antibody Testing ... More results from


INSTI™ HIV-1 Antibody Test  

Center for Biologics Evaluation and Research (CBER)

... November 29, 2010 Approval Letter - INSTI HIV-1 Antibody Test Kit Indicated for the detection of antibodies to Human Immunodeficiency Virus Type ... More results from


Competitive positioning  

SciTech Connect

Changes in the utility industry are making established utility-customer relationships more vulnerable to competitors. Recent competitive forays into electric wholesale markets illustrate what's in store for utilities as customers gain more freedom of choice. For 40 years, the Borough of Butler's 19-megawatt load had been served by Jersey Central Power Light (a General Public Utilities [GPU] subsidiary). Following passage of the Energy Policy Act of 1992, the New Jersey Borough asked neighboring utility Public Service Electric Gas Co. (PSE G) to bid on its business. Just as Butler tentatively decided to sign a new contract with PSE G, other utilities joined the fray and began bidding the price down. When the dust settled, Jersey Central was given one year's cancellation notice and Butler signed a new contract with Pennsylvania Electric (another GPU subsidiary) for a 40-percent cost savings. Jersey Central's problems didn't stop there. The utility's four other municipal customers were also approached by neighboring utilities; in each case, Jersey Central lost their business (although it ultimately remained within the GPU system). The basis for success within the utility industry is shifting from operations reliability to competitive positioning. The new success model requires utilities to be market-driven, produce customer value, provide competitive versus justifiable pricing, focus more on cost productivity than on costs in rate base, and increasingly look toward forging partnerships with others. Those utilities able to successfully implement the new success model first will secure defensive and offensive competitive positions that will enable them to capitalize on changes in regulation.

Murray, W.R.



Human Antibodies to Bovine ?-Globulin  

Microsoft Academic Search

Antibodies to bovine ?-globulin (anti-BGG antibodies) were detectable by a radio-immunoassay in 70% of healthy blood donors but, generally, the titres were low. Significantly increased concentrations of anti-BGG antibodies were found in patients lacking IgA but not in patients with allergic disorders. The anti-BGG antibodies were shown to give rise to falsely high IgE values in the radio-immunosorbent test for

T. Foucard; H. Bennich; S. G. O. Johansson; U. Lundkvist



352 Anticardiolipin Antibodies in Patients with Acute Myeloid Leukemia: Prevalence and Clinical Significance  

PubMed Central

Background Leukemia in general is known to be associated with coagulopathies. The presence of antiphospholipid antibodies was associated with several medical problems, including recurrent spontaneous abortion, arterial and venous thromboses, and thrombocytopenia. A number of studies report the prevalence of anticardiolipin (ACL) antibodies in acute myeloid leukemia (AML). This study was designed to explore the prevalence and the clinical and prognostic significance of ACL antibodies in patients with acute myeloid leukemia (AML). Material and Methods The study includes 28 AML patients >15 years old and with no evidence of infection at the time of enrollment. The previous history of thromboembolism, recurrent abortion, and autoimmune disease was given from patients. Serum level of ACL antibodies was determined by indirect enzyme immunoassay. Results ACL antibodies were found in 9 patients (32.14%). None of the patients had high positive titers (>40 GPL). Two patients had moderately positive (20–40 GPL), while 7 patients had low positive (10–20 GPL) ACL antibody titers. Conclusions ACL antibody positivity was not correlated with the risk of thromboembolism, fetal loss, and autoimmune disease. These preliminary results demonstrate a prevalence of ACL antibodies in AML patients and suggest that serum ACL antibodies may have a role in some haematological malignancies. The correlation of ACL antibodies with predicting, relapse, and documenting disease activity is will be continue until 4 to 19 months of follow up.

Ayatollahi, Maryam; Ramzi, Mani; Zakerinia, Maryam; Dehghani, Mehdi



Antibody-Gold Cluster Conjugates.  

National Technical Information Service (NTIS)

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 fig...

J. F. Hainfeld



Antiphospholipid Antibodies and Venous Thromboembolism  

Microsoft Academic Search

NTIPHOSPHOLIPID antibodies (APLA) are a hetero- geneous group of antibodies that can be detected as lupus anticoagulants (LA) and anticardiolipin antibodies (ACLA).' It is generally assumed that an association exists between APLA and venous thromboembolism (VTE). This assumption is based primarily upon the results of cross- sectional studies of patients with systemic lupus erythemato- sus The results of studies in

J. S. Ginsberg; P. S. Wells; P. Brill-Edwards; D. Donovan; K. Moffatt; M. Johnston; P. Stevens; J. Hirsh



Antibody-gold cluster conjugates  


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.



Adenovirus-36 antibody status & BMI comparison among obese Missouri adolescents.  


Adenovirus-36 (Adv-36) has been implicated in the etiology of obesity. This study attempts to identify the prevalence of Adv-36 antibodies and compare BMI among obese Missouri adolescents. Thirteen obese Missouri adolescents were tested for Adv-36 antibodies via ELISA assay. Adv-36 antibodies were detected among 6 (46.2%) subjects. Mean BMI of the Adv-36 positive group and negative group was 43.5 kg/m2 and 35.4 kg/m2 (p < 0.05), respectively. This is the first such study of Adv-36 status among Missouri adolescents. PMID:23097948

Tosh, Aneesh K; Broy-Aschenbrenner, Amelia; El Khatib, Jasmine; Ge, Bin


Anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis  

Microsoft Academic Search

Objective  Prevalence and clinical significance of anti-cyclic citrullinated peptide (CCP) antibodies in Indian patients with juvenile\\u000a idiopathic arthritis (JIA).\\u000a \\u000a \\u000a \\u000a Methods  Anti-CCP antibodies were determined by enzyme-linked immunosorbent assay (ELISA) in 78 patients with JIA which included all\\u000a 3 major subtypes of the disease: pauciarticular, polyarticular afld systemic onset. Values above 5 relative units were taken\\u000a as positive. Associations between antiCCP antibodies and

R. Gupta; M. M. Thabah; B. Vaidya; S. Gupta; R. Lodha; S. K. Kabra



Transferrin-Antibody Fusion Proteins are Effective in Brain Targeting  

Microsoft Academic Search

In the present study, the receptor binding potential of transferrin (Tf) was linked to an antibody binding specificity. Human Tf was fused to mouse-human chimeric IgG3 at three positions: at the end of heavy chain constant region 1 (C_H1), after the hinge, and after C_H3. The resulting Tf-antibody fusion proteins were able to bind antigen and the Tf receptor. The

Seung-Uon Shin; Phillip Friden; Marjorie Moran; Tracy Olson; Young-Sook Kang; William M. Pardridge; Sherie L. Morrison



Specific DNA detection using antibody mediated fluorescence quenching.  


First homogenous immunoassay for sequence-specific nucleic acid detection is developed. The assay bases on our finding that a fluorophore inserted into a DNA probe instead of one of the internal nucleotides may get protected from fluorescence quenching caused by an anti-fluorophore antibody, if the probe is hybridized with the target sequence. This ensures a positive signal in the antibody presence. The assay enables quantitative detection and may have potential for development of homogenous high-throughput platforms. PMID:23246659

Sellrie, Frank; Graser, Elmara; Lenz, Christine; Hillebrand, Timo; Schenk, Jörg A



Quantitative IgE antibody assays in allergic diseases.  


During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances. PMID:10856139

Yunginger, J W; Ahlstedt, S; Eggleston, P A; Homburger, H A; Nelson, H S; Ownby, D R; Platts-Mills, T A; Sampson, H A; Sicherer, S H; Weinstein, A M; Williams, P B; Wood, R A; Zeiger, R S



Serodiagnosis of Trichomonas vaginalis infection by the indirect fluorescent antibody test.  

PubMed Central

The indirect fluorescent antibody test was used to detect antibodies to Trichomonas vaginalis in 200 antenatal patients. A total of 104 (52%) gave a positive reaction with antigen prepared from cultures of trichomonas isolated from seven of the patients. Antitrichomonal antibody was detected at a 1/4 dilution in 90% of patients with proven trichomoniasis, while the highest dilution at which antibody was detected was 1/32. IgG rather than IgM appeared to be the antibody class involved. Of those patients with no demonstrable trichomonal infection, 17% gave positive reactions at 1/4 dilution, while 64% had no demonstrable antibody. One of 30 children under 11 years of age gave a positive reaction.

Mason, P R



Interferon-beta antibodies have a higher affinity in patients with neutralizing antibodies compared to patients with non-neutralizing antibodies.  


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



Epitopes, immunoglobulin classes and immunoglobulin G subclasses of calsequestrin antibodies in patients with thyroid eye disease.  


A number of serum autoantibodies are associated with thyroid eye disease (TED), including those reactive against the calcium binding protein calsequestrin (CASQ). There are two isoforms of CASQ namely; CASQ1, found in skeletal, including extra ocular, muscle, and CASQ2, found in cardiac muscle. We determined (i) the reactivity profiles of CASQ1 and CASQ2 antibodies and (ii) the immunoglobulin (Ig) classes and IgG subclasses of CASQ1 antibodies, using enzyme-linked immunosorbent assay. Of the 20 patients with TED tested, 35% were positive for CASQ1 antibodies, 25% for CASQ2 antibodies and two patients (10%) were positive for both antibodies. Of the 12 patients with Hashimoto's thyroiditis and ophthalmopathy tested, 25% were positive for CASQ1 antibodies, 42% for CASQ2 antibodies and two patients (17%) were positive for both antibodies. CASQ1 antibodies were mainly of the IgG class and IgG1 and IgG3 subclasses. These results suggest that CASQ1 and CASQ2 do not share major epitopes. Because antibodies of the IgG1 and IgG3 subclasses are cytotoxic, CASQ1 antibodies may contribute to the eye muscle damage in patients with TED. Because CASQ1 antibodies were positive in only a third of patients with active TED we are unable to draw conclusions about their role in its pathogenesis. On the other hand, a possible role of CASQ2 antibodies in the aetiology of the cardiac complications of Graves' disease is a new avenue for research and appears worthy of further investigation. PMID:20670117

de Haan, Sofie; Lahooti, Hooshang; Morris, Olivia; Wall, Jack R



Enzyme-Linked Immunosorbent Assay for Measurement of Cytomegalovirus Glycoprotein B Antibody in Serum?  

PubMed Central

Measurement of antibody to cytomegalovirus (CMV) glycoprotein B (gB) is valuable in the assessment of the antibody response to infection and to gB-containing vaccines. For this purpose, an enzyme-linked immunosorbent assay (ELISA) with a recombinant CMV gB molecule as the antigen was evaluated. Sera from 168 anti-CMV IgG-positive and 100 seronegative subjects were used to evaluate the anti-gB antibody assay. A cutoff optical density (OD) that would distinguish gB antibody-positive from -negative sera was established. Titers of antibody to gB determined by endpoint dilution were compared with those calculated using regression analysis. The run-to-run and interoperator reproducibilities of results were measured. The mean OD + 5 standard deviations from 50 anti-CMV IgG antibody-negative sera (0.2472) was used as the cutoff between anti-gB antibody-positive and -negative results. All sera from 100 anti-CMV IgG-seronegative subjects were negative for antibody to gB. All but 1 of 168 sera from seropositive subjects were positive for antibody to gB. Observed antibody levels based on titration to the endpoint were very similar to results calculated using linear regression. The run-to-run consistency of endpoints was excellent, with 38 runs from one operator and 48 runs from another all giving results within 1 dilution of the mean value for each of three anti-CMV IgG antibody-positive serum pools. The geometric mean titer of antibody to gB for 99 sera from seropositive blood donors was 1/10,937. This ELISA gives accurate and reproducible results for the relative quantity of anti-CMV gB IgG in serum over a wide range of antibody levels.

Hackett, Daniel J.; Zhang, Changpin; Stefanescu, Carla; Pass, Robert F.



Enzyme-linked immunosorbent assay for measurement of cytomegalovirus glycoprotein B antibody in serum.  


Measurement of antibody to cytomegalovirus (CMV) glycoprotein B (gB) is valuable in the assessment of the antibody response to infection and to gB-containing vaccines. For this purpose, an enzyme-linked immunosorbent assay (ELISA) with a recombinant CMV gB molecule as the antigen was evaluated. Sera from 168 anti-CMV IgG-positive and 100 seronegative subjects were used to evaluate the anti-gB antibody assay. A cutoff optical density (OD) that would distinguish gB antibody-positive from -negative sera was established. Titers of antibody to gB determined by endpoint dilution were compared with those calculated using regression analysis. The run-to-run and interoperator reproducibilities of results were measured. The mean OD + 5 standard deviations from 50 anti-CMV IgG antibody-negative sera (0.2472) was used as the cutoff between anti-gB antibody-positive and -negative results. All sera from 100 anti-CMV IgG-seronegative subjects were negative for antibody to gB. All but 1 of 168 sera from seropositive subjects were positive for antibody to gB. Observed antibody levels based on titration to the endpoint were very similar to results calculated using linear regression. The run-to-run consistency of endpoints was excellent, with 38 runs from one operator and 48 runs from another all giving results within 1 dilution of the mean value for each of three anti-CMV IgG antibody-positive serum pools. The geometric mean titer of antibody to gB for 99 sera from seropositive blood donors was 1/10,937. This ELISA gives accurate and reproducible results for the relative quantity of anti-CMV gB IgG in serum over a wide range of antibody levels. PMID:20219875

Hackett, Daniel J; Zhang, Changpin; Stefanescu, Carla; Pass, Robert F



Antibody-mediated radiotherapy  

SciTech Connect

Antibodies that react with antigens on the surface of tumor cells but not normal cells have great potential for cancer detection and therapy. If radiolabeled without loss of immunologic specificity, such antibodies may be able to deliver cytoxic amounts of radiation. Target- cell specificity and a high extraction coefficient are necessary with any radionuclide in order to minimize normal tissue irradiation. Tumor- cell-retention time and the rate of catabolized radionuclide will also influence ultimate applicability. Among the unanswered questions for choosing a radionuclide is the choice of particle emitter. Although classic beta emitters have been used in a number of clinical situations, they have not had a major impact on disease outcome except in diseases of the thyroid. Unfortunately, Auger emitters such as iodine 125 are cytotoxic only when localized within close proximity to the genome. On the other hand, alpha emitters such as astatine 211 eliminate the need for subcellular sequestration but not cell-specific localization. 34 references.

Bloomer, W.D.; Lipsztein, R.; Dalton, J.F.



Infertility and Antiphospholipid Antibodies  

Microsoft Academic Search

Whether antiphospholipid antibodies (aPL) play a pathogenic role in infertility is highly controversial. aPL have been suggested to represent one potential etiology of infertility, specifically in patients with unexplained implantation failure following in vitro fertilization (IVF). The rationale is appealing, as it represents a logical extension of the demonstrated pathogenicity of aPL in contributing to recurrent spontaneous abortion, where mechanisms

Lisa R. Sammaritano



PubMed Central

A rabbit antiserum against commercially available Electrophorus electricus acetylcholinesterase has been prepared. Five precipitation bands were distinguished by immunoelectrophoresis, but only three of these contained demonstrable enzyme activity. In an in vitro system, activity of the commercial enzyme or of highly purified acetylcholinesterase was inhibited by 70-82 per cent after incubation with antiserum. Antibody specificity was demonstrated by the absence of serological cross reactions or enzyme inhibition with bovine erythrocyte acetylcholinesterase or horse serum cholinesterase. Images

Williams, R. Michael



Anti-CCR5 antibodies in sera of HIV-positive individuals 1 1 The views expressed herein are those of the authors and do not reflect the official policy of the Department of Defense or other departments of the United States government  

Microsoft Academic Search

One of the proposed mechanisms for resistance to human immunodeficiency virus-1 (HIV-1) infection is the presence of antibodies against receptor for CC-chemokines (CCR5). These antibodies, detected in sera of uninfected individuals exposed to HIV, have been shown to downmodulate surface CCR5 in vivo and are able to neutralize the infectivity of CCR5 strains in vitro. To address the potential role

Edith Grene; Ligia A Pinto; Alan L Landay; Harold A Kessler; Stephanie A Anderson; Matthew J Dolan; Gene M Shearer



Pleomorphic adenomas, adenoid cystic carcinomas and adenolymphomas of salivary glands analysed by a monoclonal antibody against myoepithelial\\/basal cells  

Microsoft Academic Search

Myoepithelial and basal cells were identified by a monoclonal antibody raised against keratin. This antibody (CK B1) which detects myoepithelial cells in normal salivary glands, labels spindle shaped and polygonal cells in pleomorphic adenomas. Most cells in adenoid cystic carcinomas and some basal cells in adenolymphomas were also positive for this antibody. The oncocytic epithelium of adenolymphoma was negative.

J. Caselitz; M. Osborn; K. Hamper; J. Wustrow; A. Rauchfuß; K. Weber



Anticentromere antibody in patients without CREST and scleroderma: association with active digital vasculitis, rheumatic and connective tissue disease  

Microsoft Academic Search

This paper looks at the problem confronting a doctor evaluating a patient with anticentromere antibody who does not have evidence of disease along the spectrum from CREST (calcinosis, Raynaud's phenomenon, oesophageal dysmotility, sclerodactyly, telangiectasia) to progressive systemic sclerosis. Of 33 people with anticentromere antibody, 21 had CREST and two had scleroderma. Of the other 10 with a positive anticentromere antibody,

J A Goldman



Antidepressant properties of antibodies to serotonin, brain-specific S100 protein, and delta sleep-inducing peptide.  


Potentiated antibodies to delta sleep-inducing peptide and S100 protein produced an antidepressant effect in Wistar rats. This effect was more pronounced after combined treatment with these antibodies. It can be assumed that these antibodies modulate neurobiological mechanisms of positive emotional reinforcement and, therefore, affect the resistance to depression associated with psychoemotional stress. PMID:12949638

Meshcheryakov, A F



Evaluation of gamma interferon and antibody tuberculosis tests in alpacas.  


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 o