2Autoimmune Diseases Research Centre, Shiraz Medical School, Shiraz University of Medical Sciences, Shiraz, Iran
3Department of Immunology
Background: Multiple Sclerosis (MS), the most common demyelinating disease of the CNS, is immunologically mediated in genetically susceptible individuals. Receptors for the Fc fragment of IgG (FcγR) might induce inflammatory responses through linking the humoral and cellular immune responses by targeting immune complexes to effector cells. Polymorphisms in some FcγR genes are associated with various infectious and autoimmune diseases, probably due to their effects on different binding capacities of encoded receptors for IgG containing immune complexes. Objective: To investigate the importance of FcγR polymorphisms in susceptibility to MS. Method: One hundred and fifty MS patients and 136 age and sex matched controls were genotyped for FcγRIIA and FcγRIIIA gene polymorphisms using PCR-RFLP method. Result: The allelic and genotypic frequencies of the FcγRIIA and FcγRIIIA did not differ significantly between the MS patients and controls. There was no association between allelic polymorphism of FcγRIIIA and severity of disease based on Expanded Disability Status Scale (EDSS) score. However, significant association between inherited FcγRIIA genotype and disease activity (p=0.001) or progression index was revealed (p=0.014). EDSS values showed that FcγRIIA (H/H) and (H/R) genotypes were associated with a lower EDSS score in relapsing-remitting MS and in the total MS population (P=0.001) but not (R/R) genotype. Conclusion: Considering the detrimental role of autoantibodies in the pathogenesis of MS, our results suggest that the inherited FcγRIIA alleles could affect the severity of MS by influencing the clearance rate of immune complexes and autoantibodies. The results of the present study add the FcγRIIA gene to the gene networks which determine the severity of MS in southern Iran.