Comparison of rheumatoid factors of rheumatoid arthritis patients, of individuals with mycobacterial infections and of normal controls: evidence for maturation in the absence of an autoimmune response

摘要

AbstractWe analyzed the rheumatoid factors (RF) produced by Epstein‐Barr virus‐transformed monoclonal B cells established from four patients with rheumatoid arthritis (RA), three individuals with a history ofMycobacterium tuberculosis(TB) and four normal controls (NI). Fifty‐eight RF were analyzed for specific activity (international units‐RF/μg) for the Fc part of IgG and their interaction with tetanus toxoid (TT) and DNA (polyspecificity). Furthermore, we sequenced the V‐D‐J heavy chain region of 16 (9TB‐/7RA‐) RF. Significant differences were observed between the NI‐RF and the TB‐ and RA‐RF. While the RF repertoire of normal individuals comprised of low‐avidity RF of which the majority (15/17) were polyspecific, more than half of the TB‐ and RA‐RF were monoreactive. Furthermore, the monospecific TB‐ and RA‐RF were of significantly higher avidity than the NI‐RF (RA>TB ≫ NI). With respect to poly‐specificity, the RF in the three groups were comparable: the interaction with DNA, TT as well as with Fc was inhibited either by an increase of the ionic strength to 0.3–0.5 M NaCl or by addition of the polyanion dextran sulfate, indicating that the antibodies interacted with similar anionic epitopes shared by the three antigens. Analysis of the V‐D‐J heavy chain regions showed significant differences between the respective RF. The salt‐sensitive binding was highly correlated with the presence of arginine in the complementarity‐determining region 3 (CDR3). Furthermore, whereas the polyspecific RF consisted predominantly of germ‐line encoded antibodies, the genes of the monospecific RA/TB‐RF were somatically mutated (RA>TB). It is therefore likely that maturation of RF can be initiated by chronic infections and that monospecific, somatically mutated RF ar