V158F polymorphism of FCGR3A gene in the etiopathogenesis of sarcoidosis

Genetic, infectious factors, as well as autoimmunity are considered in an etiopathogenesis of sarcoidosis (SA). We found a higher concentration of circulating immune complexes (ICs) with mycobacterial heat shock proteins from patients with sarcoidosis. This immunocomplexemia may be caused by a function disorder of receptors for Fc fragment of immunoglobulin G (FcγR), especially FcγRIIIa, encoded by FCGR3A gene because of V158F polymorphism of FCGR3A , which causes decreased affinity of FcγRIIIa to ICs with their following decreased clearance. Thus, we genotyped 77 SA patients and 143 healthy controls using polymerase chain reaction with sequence specific primers. We showed a significantly higher presence of 158F allele and 158FF homozygotes, and lower occurrence of 158FV heterozygotes in Stage I of SA (n=23), in comparison to controls. In contrast, in Stage II of SA (n=54), we revealed an increase in 158VV homozygotes when compared to controls. Additionally, we found a significant increase of 158FF homozygotes in Stage I vs II. We also showed an opposite occurrence of FCGR3A alleles in Stage I and II of SA with an increase of 158F allele in Stage I and 158V in Stage II of sarcoidosis. Hence, V158F polymorphism of FCGR3A gene may cause immunocomplexemia in our SA patients and lead either to development of Stage I (allele 158F and genotype 158FF), or to chronic course of the disease in Stage II (allele 158V and genotype 158VV). Therefore, it may serve as a prognostic biomarker of a clinical course of the disease. Funding: grant 5160/B/P01/2010/39, grant MN-31.