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