HLA genotype as a marker of multiple sclerosis prognosis: A pilot study.
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.


METHODS
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.
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium. Electronic address: andreas.Lysandropoulos@erasme.ulb.ac.be.
Andreas P
AP
Lysandropoulos
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Nicolas
N
Mavroudakis
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Massimo
M
Pandolfo
Department of Neurology, Hôpital Erasme, Université Libre de Bruxelles, Belgium.
Kaoutar
K
El Hafsi
Icometrix, Begaultlaan 1b, 3012 Leuven, Belgium.
Wim
W
van Hecke
Icometrix, Begaultlaan 1b, 3012 Leuven, Belgium.
Anke
A
Maertens
Icometrix, Begaultlaan 1b, 3012 Leuven, Belgium.
Thibo
T
Billiet
Icometrix, Begaultlaan 1b, 3012 Leuven, Belgium.
Annemie
A
Ribbens
D000328:Adult; D000368:Aged; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D015235:HLA-B Antigens / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000000981:diagnostic imaging / Q000235:genetics*; D010865:Pilot Projects; D055815:Young Adult
D015235:HLA-B Antigens
Clinical score; HLA genotype; Magnetic resonance imaging; Multiple sclerosis; Prognostic