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Published on: December 9, 2015
HLA-DRB1*1501 influences long-term disability progression and tissue damage on MRI in relapse-onset multiple
Wallace J Brownlee1, Carmen Tur2, Andreea Manole3
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Institute of Neurology, London, UK.
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.
