High avidity cytokine autoantibodies in health and disease: pathogenesis and mechanisms.
ABSTRACT Numerous reports have documented the presence of autoantibodies working against naturally occurring cytokines in humans in health and disease. In most instances, their physiological and pathophysiological significance remains unknown. However, recent advances in the methodologies for detecting cytokine autoantibodies and their application in research focused on specific disorders have shown that some cytokine autoantibodies play an important role in the pathogenesis of disease. Additionally, levels of cytokine autoantibodies may also correlate with disease severity and progression in certain infectious and autoimmune diseases but not in others. This suggests that cytokine-specific pathogenic differences exist. While multiple lines of evidence support the notion that high avidity cytokine autoantibodies are present and likely to be ubiquitous in healthy individuals, their potential physiological role, if any, is less clear. It is believed that they may function by scavenging pro-inflammatory cytokines and thereby inhibiting deleterious 'endocrine' effects, or by serving as carrier proteins, providing a 'reservoir' of inactive cytokines and thus modulating cytokine bioactivity. A central hypothesis is that sustained or repeated high-level exposure to cytokines triggers defects in T-cell tolerance, resulting in the expansion of existing cytokine autoantibody-producing B cells.
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ABSTRACT: To evaluate (1) to what extent sera from healthy subjects and patients with rheumatoid arthritis (RA) contain antibodies to bovine serum albumin (BSA); and (2) if anti-BSA antibodies interfere with results of enzyme-linked immunoassays (ELISA) containing BSA. The ELISA used was a previously developed in-house assay of autoantibodies to tumor necrosis factor (TNF). Anti-TNF and anti-BSA antibodies were analyzed by ELISA in 189 patients with early RA and 186 healthy blood donors. TNF preparations containing either BSA or human serum albumin (HSA) as carrier proteins were used as antigens in the anti-TNF assay. The presence and levels of antibodies were analyzed in relation to disease course and to the presence/absence of rheumatoid factor (RF). In patients with RA, anti-TNF/BSA levels strongly correlated with anti-BSA levels (r = 0.81, p < 0.001), whereas anti-TNF/HSA did not (r = -0.09). Neither the presence nor the levels of anti-BSA in RA patients were associated with disease progression, and antibody levels were not significantly altered compared to controls (p = 0.11). IgG reactivity with TNF/HSA was neglible. In paired sera, preincubation with BSA abolished the anti-TNF/BSA reactivity. There were no indications of RF interference with anti-BSA or anti-TNF reactivity. Antibodies to BSA are common in patients with RA as well as in healthy individuals. Their presence does not seem to be associated with RA disease activity or disease course, but may severely interfere with ELISA containing BSA. The use of BSA as a "blocking agent" or carrier protein in immunoassays should therefore be avoided.The Journal of Rheumatology 11/2010; 38(2):215-20. DOI:10.3899/jrheum.100690 · 3.17 Impact Factor
- European Urology Supplements 03/2011; 10(2):192-192. DOI:10.1016/S1569-9056(11)60573-3 · 3.37 Impact Factor
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ABSTRACT: Autoantibody against interferon is associated in many viral and non-viral diseases. This study aimed to determine the prevalence of anti-IFN-alpha autoantibodies in healthy Egyptian blood donors. The study included 558 (100 females (17.92%) and 458 males (82.08%)) Egyptian healthy blood donors who showed normal levels of liver enzymes and kidney tests and were conformed negative for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies (Abs), HIV-1/2 Abs, anti-HBc and Treponema Abs. Autoantibody against IFN-alpha-1a and IFN-alpha-2b were screened using ELISA. Anti-IFN-alpha-1a positive cases were found to be 43 subject (7.76%; 6 females (1.08%); 37 males (6.68%)) and anti-IFN-alpha-2b positive cases were found to be 3 (0.54%; all males). Combined positivity against both IFN-alpha-1a and IFN-alpha-2b was 38 (6.86%; 7 females (1.26%) and 31 males (6.60%)). From these findings we can conclude that antibodies against IFN-alpha are present in considerable number at low titer in accepted blood donors.Cellular Immunology 08/2011; 271(2):365-70. DOI:10.1016/j.cellimm.2011.08.002 · 1.87 Impact Factor