The exploration of joint-specific immunoreactions on immunoglobulins G of anti-glucose-6-phosphate isomerase antibody-positive patients with rheumatoid arthritis
The pathogenic role of autoantibodies in rheumatoid arthritis (RA) remains elusive. Anti-glucose-6-phosphate isomerase (GPI) antibodies (Abs) are candidates for arthritogenic Abs because they directly induce arthritis in mice. High titers of anti-GPI Abs are found in some RA patients with severe forms. The aim of this study was to analyze the role of IgG, including anti-GPI Abs, in the joints of RA patients. Synovial tissue was obtained from 6 patients with RA (3 anti-GPI Abs- positive and 3 anti-GPI Abs- negative) and compared histologically and immunohistochemically for IgG and C3 deposition. IgG fractions were separated from the sera of anti-GPI Abs-positive RA patients and healthy subjects, and injected into the metacarpophalangeal joints of 4 cynomolgus monkeys. On day 16, the joints were harvested and examined histologically and immunohistochemically. The expression of the C5a receptor (C5aR) molecule in the synovium was quantified by real-time PCR using cDNA from the monkeys' joints. The synovia of anti-GPI Abs-positive RA patients showed diffuse infiltration of cells, including mast cells, and strong deposition of IgG and C3. In monkeys, IgG from RA patients, including anti-GPI Abs, resulted in recruitment of granulocytes and mononuclear cells, strong deposition of IgG on the articular surface, and overexpression of C5aR, but no joint swelling. No infiltrated cells or IgG deposition were observed in monkeys injected with IgGs from healthy subjects. Our results suggest that IgG fraction from RA patients, including that of anti-GPI Abs, may play a role in the synovitis of RA, although the pathogenesis of human anti-GPI Abs is still uncertain.
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Document Type: Research Article
Affiliations: Division of Rheumatology, Institute of Clinical Medicine, University of Tsukuba, Tsukuba 305-8575, Japan., Email: [email protected]
Publication date: November 1, 2005
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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