HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis

Wallace J Brownlee; Carmen Tur; Andreea Manole; Arman Eshaghi; Ferran Prados; Katherine A Miszkiel; Claudia Am Gandini Wheeler-Kingshott; Henry Houlden; Olga Ciccarelli

doi:10.1177/13524585221130941

HLA-DRB11501* influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis

Mult Scler. 2023 Mar;29(3):333-342. doi: 10.1177/13524585221130941. Epub 2022 Nov 18.

Authors

Wallace J Brownlee¹, Carmen Tur², Andreea Manole³, Arman Eshaghi¹, Ferran Prados⁴, Katherine A Miszkiel⁵, Claudia Am Gandini Wheeler-Kingshott⁶, Henry Houlden⁷, Olga Ciccarelli⁸

Affiliations

¹ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK.
² NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK/UK e-Health Center, Universitat Oberta de Catalunya, Barcelona, Spain.
³ Salk Institute for Biological Studies, San Diego, CA, USA.
⁴ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK/Centre for Medical Image Computing, Department of Medical Physics and Biomedical Engineering, University College London, London, UK.
⁵ Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, UK.
⁶ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK/Brain Connectivity Center, C. Mondino National Neurological Institute, Pavia, Italy Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
⁷ Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London, UK.
⁸ NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK/NIHR University College London Hospitals Biomedical Research Centre, London.

PMID: 36398585
DOI: 10.1177/13524585221130941

Abstract

Background: Whether genetic factors influence the long-term course of multiple sclerosis (MS) is unresolved.

Objective: To determine the influence of HLA-DRB1*1501 on long-term disease course in a homogeneous cohort of clinically isolated syndrome (CIS) patients.

Methods: One hundred seven patients underwent clinical and MRI assessment at the time of CIS and after 1, 3, 5 and 15 years. HLA-DRB1*1501 status was determined using Sanger sequencing and tagging of the rs3135388 polymorphism. Linear/Poisson mixed-effects models were used to investigate rates of change in EDSS and MRI measures based on HLA-DRB1*1501 status.

Results: HLA-DRB1*1501 -positive (n = 52) patients showed a faster rate of disability worsening compared with the HLA-DRB1*1501 -negative (n = 55) patients (annualised change in EDSS 0.14/year vs. 0.08/year, p < 0.025), and a greater annualised change in T2 lesion volume (adjusted difference 0.45 mL/year, p < 0.025), a higher number of gadolinium-enhancing lesions, and a faster rate of brain (adjusted difference -0.12%/year, p < 0.05) and spinal cord atrophy (adjusted difference -0.22 mm²/year, p < 0.05).

Interpretation: These findings provide evidence that the HLA-DRB1*1501 allele plays a role in MS severity, as measured by long-term disability worsening and a greater extent of inflammatory disease activity and tissue loss. HLA-DRB1*1501 may provide useful information when considering prognosis and treatment decisions in early relapse-onset MS.

Keywords: Clinically isolated syndrome; genetics; multiple sclerosis; prognosis.

MeSH terms

Chronic Disease
Demyelinating Diseases*
Genetic Predisposition to Disease
HLA-DRB1 Chains / genetics
Humans
Magnetic Resonance Imaging
Multiple Sclerosis* / pathology
Neoplasm Recurrence, Local

Substances

HLA-DRB1 Chains