IGG3 REACTIVE RHEUMATOID-FACTOR IN RHEUMATOID-ARTHRITIS - ETIOLOGIC AND PATHOGENIC CONSIDERATIONS

Rheumatoid factor (RF) is a polyclonal autoantibody directed against t he Fc portion of IgG. Although the role of RF in patients with rheumat oid arthritis (RA) is unclear, immune complexes that form between RF a nd IgG can activate the classical complement (C) pathway, leading to p athogenic outcomes involving inflammatory events and tissue damage. Th e specificity of serum RF and RF produced by rheumatoid synovial cells (RSC) is different. Serum RF has specificity for rabbit IgG and human IgG subclasses IgG1, 2, and 4, but binds poorly to IgG3. The affinity of serum RF for IgG Fc is low, having an association constant of 10(4 )-10(5) M(-1). RSC RF, however, has specificity for human IgG and high avidity for IgG3. Because of this greater specificity and avidity for IgG3, and because RSC RF may be pathogenically more important than se rum RF, an important role for IgG3-reactive RF in RA may exist. Bindin g of RF to IgG may be dependent on the allotype and glycosylation of I gG. Infectious agents present in RA patients may directly or indirectl y induce the production of certain RF. In this communication, we revie w and expand on several observations examining the role of IgG3-reacti ve RF in RA including: 1) binding differences between RF derived from RSC and serum; 2) glycosylation characteristics of IgG and its interac tion with RF; 3) apparent allotype dependent binding of IgG3-reactive RF; and 4) possible relationship between infectious agents and the pro duction of IgG3-reactive RF. Taken together, these observations sugges t an important role for IgG3-reactive RF in better understanding the e tiology and pathogenesis of RA.