Isolation, Characterization, and Molecular Modeling of a Rheumatoid Factor from a Hepatitis C Virus Infected Patient with Sjögren's Syndrome

Lee, Yu-Ching; Tsai, Keng-Chang; Leu, Sy-Jye; Wang, Tuan-Jen; Liu, Chia-Yu; Yang, Yi-Yuan

Rheumatoid factors (RFs) are antibodies directed against the Fc part of autologous IgG and are the most characteristic marker in rheumatoid arthritis (RA), a chronic joint inflammation with unknown etiopathogenesis [7, 8] . Complex formation between RF and IgG may lead to activation of complement and other inflammatory mediators directly [9] . Physiological RF mainly belongs to IgM isotype. It serves a beneficial role in host defense which facilitates the clearance of antigen by enhancing complement activation and phagocytosis. Oppositely, pathological RF is associated with RA and other systemic autoimmune diseases [10, 11] . Monospecific IgG RFs are implicated in causing inflammation and tissue damage in the rheumatoid synovium [1, 7] . Corper et al. were the first group to visualize RF binding by crystal structure directly showing an epitope spanning the junction of the C 2 and C 3 domains on Fc fragment [12] . In another study, Duquerroy et al. determined a different epitope recognition site using their IgM RF [13] . Their definite C 3-C 3 interface, including the C-terminal region of both heavy chains, is distant from the previously identified C 2-C 3 interface [12] . Both complexes were generated from IgM RF origin and indicated the involvement of somatic mutations in the interaction interface.