Immunoglobulin G Fc-receptor (FcγR) IIA and IIIB polymorphisms related to disability in MS

Abstract

Objective: MS is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of immunoglobulin G (IgG) (FcγR) link the humoral and cellular immune responses by targeting immune complexes to effector cells. Different FcγR show variability in their distribution, strength, and capacity of binding different IgG subclasses. Methods: To investigate the role of FcγR in MS, 136 MS patients and 96 matched controls were genotyped for FcγRIIA and FcγRIIIB gene polymorphisms; the results were correlated to disease susceptibility and severity measured by the Expanded Disability Status Scale (EDSS). Results: The allele frequencies of the FcγRIIA and FcγRIIIB did not differ significantly between the MS patients and the controls. Patients homozygous for the FcγRIIIB neutrophil antigen (NA) 1 allele had a significantly more benign course of MS than patients heterozygous or homozygous for the FcγRIIIB NA2 allele. Patients homozygous for the FcγRIIA histidine (H) allele also had a more benign course of MS than patients heterozygous or homozygous for the FcγRIIA arginine (R) allele. Conclusion: The results implicate FcγRIIIB and to a lesser extent FcγRIIA as disease-modifying genes in MS. FcγRIIIB NA1/NA1 and FcγRIIA H/H bind more efficient IgG1/IgG3 and IgG2 subclasses, respectively, than FcγRIIIB NA2/NA2 and FcγRIIA R/R. A more effective processing of circulating immune complexes may be one mechanism for better clinical outcome in MS.