Association of Fcγ receptor IIIA variant with a subset of anti-topoisomerase I-positive patients in systemic sclerosis: a descriptive pilot study

Hypothesizing a pathophysiological role of anti-topoisomerase I antibodies (anti-topo I) through autoantibody-dependent cell-mediated cytotoxicity (ADCC) and cytotoxic effectors expressing receptors for the Fc portion of IgG in systemic sclerosis (SSc), 267 SSc patients (56 with anti-topo I and 102 with anti-centromere antibodies (ACA)) were genotyped for the functional FCGR3A -V158F polymorphism. A descriptive analysis of patients according to their clinical and immunological status and FCGR3A -158 V/F genotypes was performed using multiple correspondence analysis. This descriptive analysis revealed an association between the FCGR3A -158 VV genotype and the presence of anti-topo I. By contrast, no relationship was found between FCGR3A polymorphism and the presence of ACA. SSc patients with anti-topo I appear to be more frequently homozygous for the high-affinity FcγRIIIA-coding allele, suggesting that some autoantibodies may be pathogenic through ADCC.