Abstract:
OBJECTIVE:In addition to the main multiple sclerosis (MS) major histocompatibility complex (MHC) risk allele (HLA DRB1*1501), investigations of the MHC have implicated several class I MHC loci (HLA A, HLA B, and HLA C) as potential independent MS susceptibility loci. Here, we evaluate the role of 3 putative protective alleles in MS: HLA A*02, HLA B*44, and HLA C*05. METHODS:Subjects include a clinic-based patient sample with a diagnosis of either MS or a clinically isolated syndrome (n = 532), compared to subjects in a bone marrow donor registry (n = 776). All subjects have 2-digit HLA data. Logistic regression was used to determine the independence of each allele's effect. We used linear regression and an additive model to test for correlation between an allele and MRI and clinical measures of disease course. RESULTS:After accounting for the effect of HLA DRB1*1501, both HLA A*02 and HLA B*44 are validated as susceptibility alleles (p(A*02) 0.00039 and p(B*44) 0.00092) and remain significantly associated with MS susceptibility in the presence of the other allele. Although A*02 is not associated with MS outcome measures, HLA B*44 demonstrates association with a better radiologic outcome both in terms of brain parenchymal fraction and T2 hyperintense lesion volume (p = 0.03 for each outcome). CONCLUSION:The MHC class I alleles HLA A*02 and HLA B*44 independently reduce susceptibility to MS, but only HLA B*44 appears to influence disease course, preserving brain volume and reducing the burden of T2 hyperintense lesions in subjects with MS.
journal_name
Neurologyjournal_title
Neurologyauthors
Healy BC,Liguori M,Tran D,Chitnis T,Glanz B,Wolfish C,Gauthier S,Buckle G,Houtchens M,Stazzone L,Khoury S,Hartzmann R,Fernandez-Vina M,Hafler DA,Weiner HL,Guttmann CR,De Jager PLdoi
10.1212/WNL.0b013e3181ed9c9csubject
Has Abstractpub_date
2010-08-17 00:00:00pages
634-40issue
7eissn
0028-3878issn
1526-632Xpii
75/7/634journal_volume
75pub_type
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