Polymorphism of FCGR3A gene in sarcoidosis

We showed increased level of immune complexes (ICs) with mycobacterial heat shock proteins (Mtb-hsp) and increased expression of receptors for Fc fragment of immunoglobulin G (Fc gamma R) I-III on blood monocytes with their increased phagocytic activity, responsible for clearance of these ICs in sarcoidosis (SA). Since Fc gamma RIlla is the most crucial in this process, we genotyped 77 SA patients and 143 healthy controls with polymerase chain reaction for V158F polymorphism of FCGR3A gene, encoding Fc gamma RIIIa. We revealed significantly higher percentage of 158F and 158FF and lower of 158FV variants in Stage I of SA versus controls. Conversely, in Stage II of SA, we found increase in 158VV homozygotes versus controls. We also showed significant increase of 158F and 158FF variants in Stage I vs II and of 158V in Stage H vs I. Therefore, in Stage I, 158F allele may cause decreased Fc gamma RIlla affinity and clearance of ICs, whereas in Stage II, 158V allele may cause effective Fc gamma RIIla affinity to ICs with e.g. mycobacteria, their phagocytosis, Mtb-hsp secretion with ICs formation, Mtb-hsp epitope spread and subsequent immune reaction. Thus, VI 58F polymorphism of FCGR3A may explain the immunocomplexemia in our patients and might serve as prognostic marker of clinical course of sarcoidosis. (C) 2014 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.