FcγRII and multi-system autoimmune disease

Abstract

The FcR are a crucial link in the immune response between humoral and cellular immunity and cell-based effector systems, mediating a wide variety of physiological and biochemical responses. The FcR for IgG (FcgammaR) and in particular the most widely expressed of these, FcgammaRII, are important in regulating adaptive immunity. Disruption of their function is a key factor in the development of autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), which are characterized by chronic, multi-organ inflammation. Studies of the FcgammaRII include structure/function relationships, investigation of the associations between FcR polymorphisms and human disease and animal studies using knockout or transgenic mouse models. These investigations showed that the various forms of FcgammaRII interact with immune complexes to either initiate or inhibit inflammation. In conjunction with environmental antigens and genotype, the FcgammaRII activating and inhibitory receptors determine the nature and magnitude of response to antigens. In this review, the structure and function of the FcgammaRIIs and their role in immune complex-mediated auto-immunity are discussed.

Long-term persistence of clinical symptoms in dengue-infected persons and its association with immunological disorders

“…25 As such, the IC deposits may induce an acute inflammatory reaction, clinically translated as inflammatory pain in muscles and joints. 4 Allelic variance of FcgRIIa with a single nucleotide polymorphism (SNP) changing amino acid 131, determines the binding affinity for IgG1. 26,27 Arginine (R) at 131 results in an increased ability to bind IgG1, while histidine (H) at 131 reduces binding of IgG1.…”

“…In this capacity, increased expression of activating FcR, including FcgRIIa, on monocytes and macrophages has been associated with a subsequent increase in production of inflammatory cytokines. 4 While the acute manifestations of dengue are well known, 5 only a limited number of studies have reported the unique clinical manifestations occurring during the early convalescent phase of infection, which may have an autoimmune component in their development. [6][7][8][9] Further, the longterm consequences of the cross-reactivity of dengue antibodies and their effect on plasmin activity, 10 which may increase the long-term risks of hemorrhage among infected patients, also remain unknown.…”

“…This study was undertaken to evaluate the sequelae of dengue disease in the 2 years following infection. Given the mediating effect of the FcR in symptomatic dengue disease 11,12 and its role in the development of autoimmune disorders, 13 we also carried out additional immunological and genetic analyses to ascertain whether persisting clinical manifestations among infected individuals are associated with alterations consistent with an autoimmune-based disorder.…”

Inhibition of destructive autoimmune arthritis in FcγRIIa transgenic mice by small chemical entities

“…Fcgamma receptors (FcgRs) provide crucial links between humoral and cellular immune responses, and as such are important in immune homeostasis and response to pathogens. 1 FcgR interactions with immune complexes can, however, lead to cellular activation, triggering an inflammatory cascade and tissue destruction. 2 Five subclasses of FcgR are known in humans, including four activating receptors (FcgRI, FcgRIIa, FcgRIIIa and FcgIIIb), and one inhibitory receptor (FcgRIIb).…”

Chronic symptoms persisting after travel-related infections

“…Non-neutralizing antibodies circulating in the serum of the patients enhance viral entry through the Fc receptor and worsen the course of infection [49]. An increased expression of Fc activating receptors on the monocytes and macrophages is associated with an increase in the production of inflammatory cytokines [50]. The following autoimmune markers were assessed in a subset of asymptomatic individuals: complement factors C3/C4, rheumatoid factor (RF), C-reactive protein (CRP), antinuclear antibodies (ANA), and immune complexes (IC).…”