HLA-DR15 is associated with lower age at onset in multiple sclerosis

To date, more than a dozen studies have investigated the role of HLA genes in determining clinical course and disease severity in multiple sclerosis ( MS); in each of these studies, however, patient sample size has been small, and no consistent pattern has emerged from the results. For the present st udy, we determined HLA class II genotypes and catalogued clinical and demog raphic data for a total of 948 patients, making our data set the largest ev er used to investigate HLA genes in MS. Our goals were both to investigate the impact of HLA-DRB1 alleles on clinical course and disease severity in M S and to compare the frequencies of the established susceptibility allele D R15 in various clinicodemographic subgroups of MS patients. We found that, in addition to DR15, DR17 is positively associated with susceptibility to M S; that none of the HLA-DRB1 alleles influences course or outcome in MS; th at carriers of DR15 are prone to MS development at an earlier age than nonc arriers; and that differences in DR15 positivity rates, after stratificatio n for diagnostic category and examination results, seem to reflect a gradie nt of phenocopy contamination, with rates increasing in proportion to the d egree of clinical or paraclinical verification of the MS diagnosis.