The HLA-DR13 haplotype is associated with “benign” multiple sclerosis in northeast Italy

Abstract

MS is currently considered an organ-specific autoimmune disease and an excellent paradigm of the “complex trait disorders.” Indeed, genetic and epidemiologic studies indicate that both genes and environmental factors are involved in MS development and advance a complex polygenic inheritance pattern of susceptibility. In several geographic areas, the HLA-DRB1\*1501,DQA1\*0102,DQB1*0602 haplotype is associated with the disease, but it is now recognized that HLA antigens contribute only modestly to overall susceptibility.1 Only a few studies have addressed the identification of resistance alleles,2-4⇓⇓ but there are no convincing data on the association of peculiar HLA antigens with the clinical course of MS. We defined the relapsing-remitting form of MS (RRMS) that produced an expanded disability status scale (EDSS) score ≤ 3 with normal neuropsychological examination in a period of 15 or more years after clinical onset of the disease as benign, and secondary-progressive MS (SPMS) that reached EDSS ≥ 6 within 5 years of disease onset as malignant. In a population of 500 MS patients attending the MS Center of the Veneto Region (northeast) of Italy, we identified 30 patients with benign RRMS, and 25 patients with malignant SPMS. All of the patients’ ancestors were from …