Systemic humoral autoimmunity but joint-specific inflammation: The syndrome of rheumatoid arthritis

✍ Scribed by Xiaobo Wu; Fei Shih; John P. Atkinson

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 102 KB
• Volume: 56
• Category: Article
• ISSN: 0004-3591
• DOI: 10.1002/art.22858

✦ Synopsis

In our ongoing efforts to explain the immunopathogenesis of rheumatoid arthritis (RA), we will integrate and highlight two recent advances. The first advance is the identification of IgG autoantibodies to citrullinated peptides in a substantial (30-50%) portion of patients with RA and their role as a diagnostic marker for RA (1,2). Surprisingly, this antibody binds to a ubiquitous autoantigen, citrullinated peptide, yet leads to a joint-specific disease. The mechanism through which anti-citrullinated peptide antibodies mediate joint disease is unknown. However, clues to their pathogenesis in RA can be deduced from the K/BxN mouse model of arthritis. The second advance, the K/BxN mouse model, features IgG autoantibodies that likewise bind to a ubiquitous self antigen, glucose-6-phosphate isomerase (GPI), resulting in joint-centered pathology. Analogous to immune complex-mediated glomerulonephritis, we propose a disease paradigm in which joints serve as a repository for autoantibodies, culminating in immune complex formation and subsequent immune activation and synovitis.