The FcgammaRIIIA-158V allele is a risk factor for ITP

Abstract

In those patients with idiopatic thrombocytopenic purpura (ITP) that do not respond to standard therapy with corticosteroids and/or splenectomy, high-dose intravenous IgG or low dose anti-D is given to achieve transient increases in circulating platelet counts. The effect of these treatments is thought to be blockade of macrophage Fc receptors. Macrophages express FcγRIa, FcγRIIa and FcγRIIIa, all three classes may be involved in binding and phagocytosis of sensitized platelets. The FcγRIIa-131R/H and FcγRIIIa-158V/F polymorphisms influence the IgG-binding affinity of the receptors. In literature, skewing of distribution of the FcγRIIA alleles towards the low-affinity-genotype: FcγRIIA-131R/R has been described in ITP patients. Others did not confirm these findings. We genotyped a group of 83 patients with chronic ITP and 87 ethnically comparable hospital controls for the FcγRIIA, FcγRIIIA and FcγRIIIB polymorphisms, the latter Fc receptor is only expressed by neutrophils. In the ITP patient population, the gene frequency of the FcγRIIIA-158V allele was 0·55, vs. 0·43 in the control population (P = 0·001). The genotype distribution of the FcγRIIIA-V/F polymorphism was also significantly different from that of a control population (P = 0·006). The allele and genotype distributions of the FcγRIIA-131R/H or the FcγRIIIB-NA1,2 polymorphisms was similar in patients and controls. Our observations show that macrophage FcaRIIIa may be the most important receptor in clearance of sensitized platelets, or that FcγRIIIa-bearing cells (NK cells or macrophages) are implicated in the pathogenesis of this autoimmune disease.