Is multiple sclerosis progression associated with the HLA-DR15 haplotype?

Klarissa Hanja Stürner; Inessa Siembab; Gerhard Schön; Jan-Patrick Stellmann; Nika Heidari; Boris Fehse; Christoph Heesen; Thomas H Eiermann; Roland Martin; Thomas Mc Binder

doi:10.1177/2055217319894615

Is multiple sclerosis progression associated with the HLA-DR15 haplotype?

Mult Scler J Exp Transl Clin. 2019 Dec 9;5(4):2055217319894615. doi: 10.1177/2055217319894615. eCollection 2019 Oct-Dec.

Affiliations

¹ Institute for Neuroimmunology and Clinical MS Research, University Medical Center Hamburg-Eppendorf, Germany.
² Department of Medical Biometry and Epidemiology, University Medical Center Hamburg-Eppendorf, Germany.
³ Research Department Cell and Gene Therapy, University Medical Center Hamburg-Eppendorf, Germany.
⁴ HLA Laboratory, University Medical Center Hamburg-Eppendorf, Germany.

Abstract

Background: The prevalence of multiple sclerosis is associated with the major histocompatibility complex class II DR15 haplotype HLA-DRB1*15:01∼HLA-DRB5*01:01.

Objective: To assess whether multiple sclerosis progression is associated with the main susceptibility haplotype HLA-DRB1*15:01∼HLA-DRB5*01:01.

Methods: Patients (n = 1230) and healthy controls (n = 2110) were genotyped for HLA-DRB1 and HLA-DRB5. The baseline Expanded Disability Status Scale (EDSS) score was determined and patients were followed for at least 3 years.

Results: After follow-up of the consecutive cohort 349 patients were classified as having clinical isolated syndrome and 881 patients as having multiple sclerosis. The susceptibility allele HLA-DRB1*15:01 was more frequent in clinical isolated syndrome (odds ratio 1.56) and multiple sclerosis (odds ratio 3.17) compared to controls. HLA- DRB1*15:01 was the only enriched HLA-DRB1 allele in multiple sclerosis patients. Comparison of clinical characteristics between HLA-DRB1*15:01∼HLA-DRB5*01:01 negative and positive patients with multiple sclerosis showed that baseline EDSS score, disease duration and frequency of the category secondary progressive multiple sclerosis with relapse were increased in the HLA-DRB1*15:01∼HLA-DRB5*01:01 positive group.

Conclusion: The study confirmed HLA-DRB1*15:01 and HLA-DRB5*01:01 as the main susceptibility alleles and showed weak indirect evidence for a role in progression of the disease.

Keywords: EDSS; HLA-DRB1*15:01; HLA-DRB5*01:01; Multiple sclerosis; progression.