Possible role of microbial IgG Fc-binding proteins in rheumatoid arthritis

Abstract

IgG Fc binding substances (receptors) are widespread among pathogenic microorganisms. The receptors from Staphylococcus aureus, streptococci of group A, C and G as well as Herpes-infected cells bind to the interface between the CH2 and CH3 domains i.e. to His 435, Tyr 436 and possibly also His 433 and/or 310. Most rheumatoid factors (RF) from patients with rheumatoid arthritis show a similar binding pattern. Hence, it has been shown that antibodies to microbial IgG Fc receptors (S. aureus and group A streptococci type M15) and RF are idiotypic-anti-idiotypic antibody "partners" i.e. that RF are the "internal images" of microbial IgG Fc binding proteins. Group A streptococci possessing IgG Fc receptors elicit higher titres of RF when injected in rabbits as compared to group A streptococci without IgG Fc receptors. The streptococcal IgG Fc receptors exhibit a diversity of preferences for subclasses of human IgG, some of them showing allotype preferences. Such allotypes are also recognized by certain RF. IgG RF are able to self-associate thereby forming immune complexes which can activate the complement cascade as well as stimulate release of prostaglandins and (probably) interleukin-1. Since these factors have been assigned an important pathogenic role in rheumatoid arthritis, self-aggregating IgG RF, proposed to be induced by microbial IgG Fc receptors might be an important pathogenic factor in rheumatoid arthritis because rheumatoid arthritis is the only known condition where synthesis of RF takes place in the synovia.

Autoimmune streptococcal glomerulonephritis: the problem of nephritogenicity of <i>Streptococcus pyogenes</i>

“…Эти антитела способны к агрегации и образованию активирующих комплемент комплексов, стимулирующих выброс провоспалительных цитокинов и простагландинов. Таким недавно виделся и патогенез ревматоидного артрита [24,62]. Он связан с отложениями ревматоидного фактора на синовиальной оболочке суставов и последующим ее воспалением, что возможно указывает на общность отдельных звеньев в развитии АPSGN и ревматоидного артрита.…”

Autoimmune heart disease: role of sex hormones and autoantibodies in disease pathogenesis

“…Interestingly, many of these infections are also associated with inflammatory heart diseases such as myocarditis (Box 1 & 5). The presence of RF may be useful and beneficial early in the course of a bacterial or viral infection [186–188]. RF levels are higher in secondary (e.g., 23%) compared with primary infections (e.g., 8%), and even higher in the sera of latently infected individuals (e.g., 37%) suggesting that individuals with higher RF may not be clearing infections [186].…”