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

Brownlee, Wallace J; Tur, Carmen; Manole, Andreea; Eshaghi, Arman; Prados, Ferran; Miszkiel, Katherine A; Wheeler-Kingshott, Claudia Am Gandini; ... Ciccarelli, Olga; + view all (2022) HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis. Multiple Sclerosis Journal 10.1177/13524585221130941. (In press). Green open access

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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.

Type: Article
Title: HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple sclerosis
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1177/13524585221130941
Publisher version: https://doi.org/10.1177/13524585221130941
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Clinically isolated syndrome, genetics, multiple sclerosis, prognosis
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Department of Neuromuscular Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neuroinflammation
URI: https://discovery.ucl.ac.uk/id/eprint/10161915
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