The FcγRIIa polymorphism influences production of interleukin‐1 by mononuclear cells

Abstract

The functional bi-allelic polymorphism of immunoglobulin G (IgG) Fc receptor (FcgammaR) IIa influences the efficiency of human IgG2 binding. Our previous study showed that the high affinity FcgammaRIIa genotype (-H/H131) was associated with periodontitis risk. As interleukin-1 (IL-1) is one of the major causes of periodontal tissue destruction, it is hypothesized that the FcgammaRIIa-H/H131cross-linking could induce an increased IL-1 release by mononuclear cells. In this study, we evaluated the intracellular expressions of IL-1beta in CD14 positive cells upon stimulation with human IgG2 by flow cytometry. FcgammaRIIa-H/H131 subjects exhibited a higher percentage of IL-1beta-producing cells than FcgammaRIIa-R/H131 and -R/R131 subjects (P < 0.05). These results support the concept that FcgammaRIIa genotype may affect IL-1beta production, possibly leading to interindividual differences in periodontitis risk.

Polymorphic Regions in Fc Gamma Receptor and Tumor Necrosis Factor‐α Genes and Susceptibility to Chronic Periodontitis in a Cohort From South India

“…Further, FCGR2B ‐232Ile/Thr was not found to be associated with CP in Japanese women who had a preterm delivery 39 . Presence of a higher percentage of IL‐1β‐producing cells in individuals carrying FCGR2A ‐His131His genotype compared with 131Arg allele carriers has been documented 40 . In the present study, a significant redundant interaction was found between IL1B +3954C/T and FCGR2A His/Arg in development of CP.…”

Understanding Inter-Individual Variability in Monoclonal Antibody Disposition

“…The exact role of FcγRs in disease manifestation is unclear but it has been suggested that harboring a certain FcγR phenotype could be risk factor in development of specific diseases [139]. For example, the FcγRIIa-H131 genotype was found to be associated with an increased production of the pro-inflammatory cytokine IL-1β by mononuclear cells, leading to inter-individual differences in the risk for acquiring periodontitis [140]. In multiple studies carried out in diverse ethnic populations, significant associations were found between FcγR polymorphisms and inter-individual differences in susceptibility, prevalence, and prognosis of diseases like systemic lupus erythematosus (SLE) [141][142][143][144], rheumatoid arthritis (RA) [145,146], immune thrombocytopenia [147], Guillain-Barré syndrome [148][149][150], myasthenia gravis [151] pediatric autoimmune neutropenia [152], IgA nephropathy [153], inflammatory myopathies [154], anti-glomerular basement membrane antibody disease [155], Kawasaki Disease [156], periodontitis [157,158], malaria [159,160], dengue [161], and sickle cell disease [162].…”

Immunomodulation by IVIg and the Role of Fc-Gamma Receptors: Classic Mechanisms of Action after all?

“…FcγRIIa-H131 has a higher binding affinity for IgG1 and especially IgG2, as compared to FcγRIIa-R131, but binding to IgG3 and IgG4 is similar for both variants ( 38 ). Functionally, mononuclear cells from FcγRIIa-131HH individuals produce more IL-1beta when stimulated with IgG2 than FcγRIIa-131HR and -131RR individuals ( 39 ). Similarly, neutrophils from individuals homozygous for H131 (FcγRIIa-131HH) have been shown to have increased phagocytosis and degranulation in response to serum-opsonized bacteria and increased rosette formation and phagocytosis in presence of IgG3 anti-D sensitized erythrocytes when compared to FcγRIIa-131RR individuals ( 36 , 40 ).…”