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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.
Insights
The HLA-DRB1*1501 gene variant is linked to faster disability progression and increased disease activity in multiple sclerosis (MS) patients. This finding may inform prognosis and treatment decisions for early MS.
Area of Science:
- Neuroimmunology
- Genetics of Neurological Disorders
- Multiple Sclerosis Pathogenesis
Background:
- The role of genetic factors in the long-term progression of multiple sclerosis (MS) remains incompletely understood.
- Investigating specific genetic markers can elucidate their impact on disease trajectory.
Purpose of the Study:
- To determine the influence of the HLA-DRB1*1501 allele on the long-term disease course in patients with clinically isolated syndrome (CIS).
Main Methods:
- 107 CIS patients were assessed clinically and via MRI over 15 years.
- HLA-DRB1*1501 status was determined using Sanger sequencing and rs3135388 polymorphism tagging.
- Linear/Poisson mixed-effects models analyzed changes in EDSS and MRI measures based on HLA-DRB1*1501 status.
Main Results:
- HLA-DRB1*1501-positive patients exhibited a significantly faster rate of disability worsening (EDSS change: 0.14/year vs. 0.08/year).
- Positive status correlated with greater annual increases in T2 lesion volume and more gadolinium-enhancing lesions.
- Faster rates of brain and spinal cord atrophy were observed in HLA-DRB1*1501-positive individuals.
Conclusions:
- The HLA-DRB1*1501 allele is associated with increased MS severity, evidenced by long-term disability progression and heightened inflammatory activity.
- HLA-DRB1*1501 status may offer valuable prognostic information for early relapse-onset MS, aiding treatment decisions.
