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Specific Autoantibodies (specific + autoantibody)
Selected AbstractsAnti-DNA Antibodies Cross-reacting with Laminin Inhibit Trophoblast Attachment and Migration: Implications for Recurrent Pregnancy Loss in SLE PatientsAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 3 2000FAISAL QURESHI PROBLEM: Systemic lupus erythematosus (SLE), an autoimmune disease, is associated with reduced fetal survival, recurrent abortions, and other pregnancy complications. Some of the autoantibodies found in SLE bind to laminins (LNs), which play an important role in the implantation of the fertilized ovum in humans. METHOD OF STUDY: To elucidate the role of these specific autoantibodies, chorionic villous explants from 6,7-week-old human placentas were established as organ cultures on laminin-1 (LN-1), collagen IV (CN-IV) or uncoated culture dishes. The cultures were then exposed to a mouse monoclonal anti-DNA/anti-LN-1 antibody, to human polyclonal lupus antibodies cross-reacting with LN-1, a function-blocking polyclonal antibody to LN-1, polyclonal antibodies to CN-IV, or IgG control. RESULTS: The explants attached to LN-1 and CN-IV, but not to uncoated culture dishes. LN-1 promoted migration of trophoblast, whereas CN-IV promoted migration of fibroblast-like cells. Trophoblast attachment and migration were abolished in a dose-dependent manner by all three antibodies to LN-1, but not by antibodies to CN-IV or IgG control. Furthermore, the effect of anti-LN antibodies was abolished by preincubating them with LN-1. CONCLUSIONS: These studies suggest that anti-DNA antibodies cross-reacting with LNs may play a role in early pregnancy failure in SLE patients by interfering with placental implantation. [source] Rheumatoid arthritis,specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogenARTHRITIS & RHEUMATISM, Issue 1 2010Isabelle Auger Objective Autoantibodies to citrullinated proteins are specific for rheumatoid arthritis (RA) and recognize epitopes centered by citrulline, a posttranslationally modified form of arginine. Peptidyl arginine deiminase type 4 (PAD-4), the enzyme that converts arginine into citrulline, is in itself a target for RA-specific autoantibodies. This study was undertaken to assess whether anti,PAD-4 autoantibodies interfere with citrullination in vitro in patients with RA, and to identify peptide targets of anti,PAD-4 antibodies that can activate or inhibit citrullination. Methods To test whether autoantibodies to PAD-4 influence citrullination, an in-house citrullination assay was developed using purified autoantibodies to PAD-4. To map B cell epitopes on PAD-4, 65 overlapping 20-mer peptides encompassing the entire PAD-4 were analyzed for their reactivity in RA sera. Results Autoantibodies to PAD-4 inhibited PAD-4,mediated citrullination. Three linear peptides on PAD-4 were recognized almost uniquely by PAD-4 autoantibodies in the sera of patients with RA. One peptide was located in the N-terminal, calcium-binding domain of PAD-4, while 2 other peptides were located in the C-terminal, substrate-binding domain of PAD-4. Conclusion Autoantibodies to PAD-4 inhibit in vitro citrullination of fibrinogen by PAD-4. Most anti,PAD-4,positive sera recognize peptides located both in the N-terminal domain (211,290) and the C-terminal domain (601,650) of PAD-4. [source] Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritisARTHRITIS & RHEUMATISM, Issue 7 2008Michelle L. Harris Objective Protein citrullination is an important posttranslational modification recognized by rheumatoid arthritis (RA),specific autoantibodies. One of the citrullinating enzymes, peptidyl arginine deiminase type 4 (PAD-4), is genetically associated with development of RA in some populations, although the mechanism(s) mediating this effect are not yet clear. There have been descriptions of anti,PAD-4 autoantibodies in different rheumatic diseases. This study was undertaken to investigate whether anti,PAD-4 antibodies are specific to RA, are associated with disease phenotype or severity, and whether PAD-4 polymorphisms influence the anti,PAD-4 autoantibody response. Methods Sera from patients with established RA, patients with other rheumatic diseases, and healthy adults were assayed for anti,PAD-4 autoantibodies by immunoprecipitation of in vitro,translated PAD-4. The epitope(s) recognized by PAD-4 autoantibodies were mapped using various PAD-4 truncations. PAD-4 genotyping was performed on RA patients with the TaqMan assay. Joint erosions were scored from hand and foot radiographs using the Sharp/van der Heijde method. Results PAD-4 autoantibodies were found in 36,42% of RA patients, and were very infrequent in controls. Recognition by anti,PAD-4 autoantibodies required the 119 N-terminal amino acids, which encompass the 3 nonsynonymous polymorphisms associated with disease susceptibility. Strikingly, the anti,PAD-4 immune response was associated with the RA susceptibility haplotype of PADI4. Anti,PAD-4 antibodies were associated with more severe joint destruction in RA. Conclusion Our findings indicate that anti,PAD-4 antibodies are specific markers of RA, independently associated with more severe disease, suggesting that an anti,PAD-4 immune response may be involved in pathways of joint damage in this disease. Polymorphisms in the PADI4 gene influence the immune response to the PAD-4 protein, potentially contributing to disease propagation. [source] Identification of peptides specific for antibodies in vitiligo using a phage libraryCLINICAL & EXPERIMENTAL DERMATOLOGY, Issue 6 2005Z. Jadali Summary Patients with vitiligo produce specific autoantibodies that can be detected in their sera. These antibodies are believed to play a role in the pathogenesis of this disease. A random peptide library displayed on phage is a technique that can be used to identify the epitopes that react with monoclonal and polyclonal antibodies. We used this technique to identify the epitopes that react specifically with the vitiligo autoantibodies. By screening the random peptide phage library and using ELISA, two clones that showed a higher frequency of reactivity with the antibodies in the sera of patients with vitiligo were identified. The peptides do not show any similarity with the autoantigens so far implicated in vitiligo, indicating that these epitopes may mimic conformational epitopes in proteins. [source] Simultaneous triple organ specific autoantibody profiling in adult patients with type 1 diabetes mellitus and their first-degree relatives,INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 3 2009S. Dagdelen Summary Aims:, We aimed to document prevalence and clinical presentations of seropositivities for glutamate decarboxylase (GAD)-antibody, celiac's disease (CD) and autoimmune thyroiditis (AIT) in adult patients with type 1 diabetes mellitus (T1DM), and their first-degree relatives. Methods:, Sixty-five patients with T1DM, 124 first-degree relatives and 65 healthy controls were screened for GAD-antibody, anti-thyroid peroxidase (ATPO), anti-thyroid stimulating hormone receptor (TSHR), anti-tissue transglutaminase and anti-gliadin antibodies in a matched case,control study. Results:, Prevalence of more than one seropositivity for CD-associated antibodies in T1DM-group is 6.0 times increased, compared with controls (p < 0.05). ATPO seropositivity is 5.3 times increased in T1DM group (p < 0.05), but TSHR antibody is comparable with controls (p > 0.05). Seropositivities for T1DM, AIT and CD are 4.3, 1.9 and 2.4 times more prevalent among first-degree relatives respectively, compared with controls (p < 0.05). Pathologically confirmed cases with CD among first-degree relatives were all identified at screening. In contrast, all of pathologically confirmed cases with CD in T1DM group, were either previously diagnosed or symptomatic at time of screening. In the group of patients with T1DM, 31% of seropositive cases for anti-ATPO were clinically latent for AIT, and 74% of ATPO (+) cases were identified at current screening study. Sixty-four per cent of ATPO (+) first-degree relatives were clinically latent for AIT, and 54% were identified at screening. Conclusion:, Type 1 diabetes mellitus, CD and AIT represent a significant overlap in an adult population with already-diagnosed T1DM and their first-degree relatives. With regard to clinical presentations, CD was less likely to be clinically silent than AIT among patients with T1DM. [source] | ||||||||||