The FcγRIIa polymorphism R/H131, autoantibodies against the platelet receptors GPIbα and FcγRIIa and a risk for thromboembolism in lupus anticoagulant patients

Abstract

SummaryThere is a clear propensity of individuals with lupus anticoagulant (LA) for thromboembolic disease (TE). Yet, it is not clear how individuals at risk for TE can be differentiated from those who are not. The FcγRIIa receptor is the only Fc receptor expressed by platelets. As platelets can be activated via this receptor, we have compared gene frequencies of the FcγRIIa polymorphism R/H131 in 46 and 27 patients with (LA/TE+) and without TE (LA/TE-), respectively, in an exploratory study. Furthermore, we investigated the presence of autoantibodies against FcγRIIa and/or GPIbα, which is in close proximity to the FcγRIIa and interacts with it functionally, and a possible linkage of antibody formation to HLA class II alleles. The FcγRIIa-R/R131 genotype was significantly less frequent in patients with LA compared to controls (p< 0.025). These findings were due to an increased frequency of heterozygous patients in the LA/TE+ cohort (odds ratio 6.76, 95% confidence interval 1.55 – 62.03, p< 0.008). For the first time, heterozygosity, rather than homozygosity, can be linked to disease, which may be explained by the dual function of the FcγRIIa, namely binding of antibodies to platelets and thereby their activation, and, on the other hand, clearance of antibody coated platelets by the phagocyte system. There was no correlation between the presence of anti-FcγRIIa or anti GPIbα autoantibodies and the FcγRIIa -R/H131 polymorphism, nor the incidence of TE, nor HLA class II alleles.