HLA determinants of susceptibility to multiple sclerosis in an Arabian Gulf population

Abstract

Background: An association between HLA antigens and susceptibility to multiple sclerosis (MS) has been established, especially in Caucasian populations. Such associations have not been as clearly defined in many Arab populations, where even the frequencies of specific HLA antigens remain unclear. Objective: The study was designed to (i) investigate the frequencies of HLA Class I and II antigens in Kuwaiti Arabs with MS, and; (ii) assess possible inter-relationships between HLA Class II antigens and such clinical phenotypic variables in MS as age at onset, gender, disease subtype and scale of disability. Subjects and methods: HLA Class I (A, B, C) and Class II (DR, DQ) antigens’ tissue-typing was performed by the standard complement-dependent microlymphocytotoxicity technique in two groups of ageand sex-matched Kuwaiti subjects: (i) 67 patients with definite MS (48 relapsing-remitting, 19 relapsing-progressive) and (ii) 145 unrelated healthy controls. The frequencies of specific HLA types were then compared between patients with controls, and in the former, related to specified clinical parameters. Results: The frequencies for the Class I antigens: A9, A10, A19, A33, B5 and CW4 appeared higher with the presence of MS, although the numbers of positive subjects were rather low. For the Class II antigens, frequencies of DR4, DQ5, DQ6, DQ7 and DQ8 were increased while those for DR6 and DR1 were decreased in the patients with MS. HLA types DR15 and DR4 were present at higher frequencies in patients with a younger age at disease onset; DR15 also appeared more frequent in the female patients. Conclusion: There is a trend towards an association between HLA Class II antigens (DR4, DQ6, DQ7 and DQ8) and MS in Kuwaiti subjects. Additionally, it appeared that DR4 and DR15 were more frequent in females and those with an early onset of the disease. These patterns of HLA Class II determinants of susceptibility to MS differ from reports in some other populations, and may reflect the recognized variability in genetic influence on HLA and disease expression.