Differences in the relationship of specificity to titre and functional affinity between circulating Ga- and pan-reactive IgM rheumatoid factors in rheumatoid arthritis

Objective. To determine if there are the differences in titre and functional affinity for immunoglobulin (Ig) G subclasses and glycoforms between the Ga- and pan-specific IgM rheumatoid factors (RFs) present in the sera of patients with rheumatoid arthritis (RA), and to determine whether these two broad specificities have different functional roles in RA. Methods. We used direct ELISA and modified ELISA to study the binding of IgM RF in the sera of 32 patients with RA with a range of RF titres to a panel of 14 IgG paraproteins of all four subclasses, some allotypes and different glycosylation patterns. Results. Pan-specific RFs were mostly found in RA sera with high RF titres, and these RFs generally had higher avidity. A trend towards higher avidity of RFs with higher titre was observed for pan-specific, but not for Ga-specific RFs. With increasing titre, pan-specific RFs tended to react strongly with fucosylated and bisected variants of hypogalactosylated IgG3 of G3m(bl) allotype and hypergalactosylated IgG4 of 4a allotype. Conclusion. Among high-titred pan-specific IgM RFs, there is a subpopulation responsible for strong anti-IgG activity in RA. The possible mechanisms of production of pan- and Ga-specific RFs are discussed.