Related Experiment Video
Updated: Apr 22, 2026
An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
HLA-DRB1*15 influences the development of brain tissue damage in early PPMS
Carmen Tur1, Sreeram Ramagopalan1, Daniel R Altmann1
1From the Departments of Brain Repair and Rehabilitation (C.T., B.B., Z.K., A.J.T., O.C.) and Neuroinflammation (D.R.A., D.H.M.), University College of London Institute of Neurology, UK; Multiple Sclerosis Centre of Catalonia (Cemcat) (C.T.), Neurology-Neuroimmunology Department, Vall d'Hebron University Hospital, Barcelona, Spain; Blizard Institute (S.R.), Queen Mary University of London; Medical Statistics Department (D.R.A.), London School of Hygiene and Tropical Medicine, University of London; Clinical Imaging Sciences Centre (M.C.), Brighton and Sussex Medical School, Falmer, East Sussex; and National Institute for Health Research (NIHR) University College London Hospitals (UCLH) Biomedical Research Centre, UK.
Objectives:
To investigate whether (1) there were differences between HLA-DRB1*15-positive and -negative patients at baseline, and (2) HLA-DRB1*15-positive patients showed a greater development of brain and spinal cord damage, as assessed by MRI, and greater progression of disability, during a 5-year follow-up, compared with HLA-DRB1*15-negative patients.
Methods:
HLA-DRB1*15 typing was performed in 41 patients with primary progressive multiple sclerosis (PPMS) who were recruited within 5 years of symptom onset. All patients and 18 healthy controls were studied clinically and with MRI at baseline, and every 6 months for 3 years, and then at 5 years. Magnetization transfer ratio parameters and volumes for brain gray matter and normal-appearing white matter, brain T2 lesion load, and spinal cord cross-sectional area were obtained. Patient disability was assessed at each visit using the Expanded Disability Status Scale and Multiple Sclerosis Functional Composite subscores.
Results:
There were no significant differences between HLA-DRB1*15-positive and -negative patients at baseline. HLA-DRB1*15-positive patients showed a greater decline in brain magnetization transfer ratio for gray matter and normal-appearing white matter (both p = 0.005) than HLA-DRB1*15-negative patients over 5 years, while the same parameters did not change over time in healthy controls. HLA-DRB1*15-positive patients also showed a trend toward a faster increase in brain T2 lesion load than HLA-DRB1*15-negative patients (0.29 [95% confidence interval 0.20-0.38] vs 0.21 [0.13-0.30] mL/mo, p = 0.085) and higher T2 lesion volumes at all time points (average difference [95% confidence interval]: 10.58 mL [7.09-14.07], p < 0.001) during the follow-up, after adjusting for disease duration.
Conclusions:
These findings suggest that HLA-DRB1*15 influences the progression of brain pathology in PPMS.
Related Concept Videos
01:19Multiple Sclerosis l: Introduction
00:49The Blood-brain Barrier
01:24Parkinson Disease ll: Pathophysiology