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

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