Functional influence of FcγRIIa on CR3 in the etiopathogenesis of sarcoidosis

Introduction: We revealed that mycobacterial heat shock proteins being implicated in forming immune complexes (CIs) can induce an immune response in sarcoidosis (SA). The immunocomplexemia in our SA patients with Stage I/II, not with Stage III/IV, may be a result of monocytes disorder of abilities to phagocytosis/clearance CIs, which rely on the function of receptors for Fc fragment of immunoglobulin G (FcγR) and for complement (CR). A stimulation of FcγRIIa, encoded by FCGR2A gene, can impact the CR3 function, which may cause a decreased affinity of this FcγR to ICs and their decreased clearance. Aim/Materials/Methods: Therefore, we evaluated the FcγRIIa and CR3R expression on blood monocytes, and polymorphism of FCGR2A gene in 114 SA patients and 148 healthy volunteers, using flow cytometry and PCR-SSP. Results: Our study revealed significantly increased expression of FcγRIIa and unchanged C3R on monocytes in SA patients with Stage I/II vs. Controls. Analysis of H131R polymorphism of FCGR2A gene revealed a significantly increased occurrence of 131HH and decreased frequency of 131HR in Stage III of SA vs. controls, with increased affinity of FcγRIIa to CIs and increased clearance of CIs. In SA patients with Stages I/II, we revealed a significantly decreased percentage of 131HH genotype of FCGR2A and a significant increase in an occurrence of 131HR heterozygotes in Stage I/II vs. Stage III/IV. Conclusions: Thus, H131R polymorphism of FCGR2A may cause of disorder of function of FcγRIIa with subsequent unchanged CR3 expression and decreased affinity of FcγRIIa to CIs and their decreased clearance with following immunocomplexemia in our SA patients with Stage I/II. Study was founded by grant no.02-127/07/232.