Objective: The identification of a biomarker with prognostic value is an unmet need in multiple sclerosis (MS). The objective of this study was to investigate a possible association of HLA genotype with disease status and progression in MS, based on comprehensive and sensitive clinical and magnetic resonance imaging (MRI) parameters to measure disease effects. Method: A total of 118 MS patients (79 females, 39 males) underwent HLA typing. Patient MS status was assessed at two time points in a 2-year interval, based on clinical scores (including EDSS, MSSS, T25FW, 9-HPT, SDMT, BVMT, CVLT-II) and MRI evaluations. Quantitative brain MRI values were obtained for whole brain atrophy, FLAIR lesion volume change and number of new lesions using MSmetrix. Predefined HLA patient groups were compared as of disease status and progression. Global assessment was achieved by an overall t-statistic and assessment per measurement by a Welch test and/or Mann Whitney U test. The effects of multiple covariates, including age, gender and disease duration as well as scan parameters, were also evaluated using a regression analysis. Results: The HLA-A*02 allele was associated with better outcomes in terms of MSSS, EDSS and new lesion count (Welch test p-value < 0.05). The HLA-B*07 and HLA-B*44 alleles showed a global negative effect on disease status, although none of the measurements reached significance (p-value < 0.05). Results for the HLA-DRB1*15, HLA-DQB1*06 and HLA-B*08 alleles were inconclusive. The influence of the confounding variables on the statistical analysis was limited. (C) 2017 Elsevier B.V. All rights reserved.