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Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition

journal contribution
posted on 2023-05-17, 06:46 authored by Van der Walt, A, Jim Stankovich, Bahlo, M, Bruce TaylorBruce Taylor, Ingrid van der MeiIngrid van der Mei, Simon James FooteSimon James Foote, Rubio, JP, Kilpatrick, TJ, Butzkueven, H
Background: HLA-DRB1*1501 (DR15) and other HLA class II alleles increase the risk of developing multiple sclerosis (MS). However, the contribution of genetic heterogeneity to the clinical course of MS remains controversial. We examined the influence of DR15 and other common DRB1 alleles (DRB1*01 (DR1), DRB1*03 (DR3) and DRB1*04 (DR4) on MS severity in a large, Australian, population-based cohort. Methods: We studied the association between common HLA-DRB1 alleles and genotypes and age of onset as well as three clinical disease severity descriptors: Multiple Sclerosis Severity Score, progression index), and the interval between the first and second attack in 978 patients with relapsing remitting MS and secondary progressive MS. We assessed cognition using the Symbol Digit Modalities Test in 811 patients and brain atrophy using the linear magnetic resonance imaging marker, the intercaudate ratio, in 745 patients. Results: Carrying DR15 significantly decreased the age of MS onset by 3.2 years in homozygotes and 1.3 years in heterozygotes. Carrying the HLA-DR15, -DR1, -DR3 or -DR4 alone or in combination did not affect clinical disease severity, cognition or cerebral atrophy. Conclusions: This study confirms that heterogeneity of HLA-DRB1 does not influence disease outcome in relapsing MS patients, with the exception of a younger age of onset in HLA-DR15 carriers.

History

Publication title

Multiple Sclerosis

Volume

17

Pagination

344-352

ISSN

1352-4585

Department/School

Menzies Institute for Medical Research

Publisher

Arnold

Place of publication

Hodder Headline Plc, 338 Euston Road, London, England, Nw1 3Bh

Rights statement

Copyright 2010 SAGE

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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