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Changes of immunoreactivity in α1-antitrypsin in patients with autoimmune diseases

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Abstract

Recent studies from this laboratory have shown that a monoclonal antibody prepared against a specific epitope on α1-antitrypsin is a valuable diagnostic marker for autoimmune conditions. In the present study we have further characterized this monoclonal antibody and reassessed its diagnostic value in screening samples from patients with various autoimmune conditions. α1-Antitrypsin was micropurified from patients with selected autoimmune conditions and from normal donors. The purified α1-antitrypsin isolated. from patients with autoimmune conditions and normal donors was deglycosylated losing both a mixture of exoglycosidases and endoglycosidase F. The immunoreactivity of the native and deglycosylated α1-antitrypsin was examined using both a monoclonal antibody and a polyclonal antibody in enzyme linked immunosorbent assay (ELISA) and radioimmunoassay (RIA), respectively. It was noted that α1-antitrypsin isolated from patients with autoimmune diseases generated a displacement curve dissimilar to α1-antitrypsin purified from normal donors or α1 antitrypsin from patients with autoimmune diseases subjected to deglycosylation when these samples were examined by ELISA using the monoclonal antibody. However, when the polyclonal antibody was used for these studies, no difference was found between the native and deglycosylated ga1,-antitrypsin suggesting that the monoclonal antibody recognized an epitope not detectable by the polyclonal antibody. We have also assessed the diagnostic usefulness of this monoclonal antibody using a battery of 530 serum samples obtained from patients with different autoimmune diseases and compared to normal human serum (NHS,N−66); these include: systemic lupus erythematosus (SLE,N=149), rheumatoid arthritis (RA,N=64), renal diseases (NP,N=33), liver diseases (HP,N=33), mixed connective tissue disease (MCTD,N = 12), diabetes (DB,N=40), SjÖgren's syndrome (SS,N = 41), polymyositis (PM,N=20), scleroderma (SCL,N=20), Alzheimer's disease (AZ,N=11), and patients with elevated levels of carcinoembryonic antigen (CEA,N=41). The results of this study demonstrated that this monoclonal antibody is positively correlated with SLE and SS. The significance of the monoclonal antibody in connection with the pathogenesis of autoimmune diseases was discussed.

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Saso, L., Silvestrini, B., Lahita, R. et al. Changes of immunoreactivity in α1-antitrypsin in patients with autoimmune diseases. Inflammation 17, 383–400 (1993). https://doi.org/10.1007/BF00918999

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