title: HLA-DRB1*15 influences the development of brain tissue damage in early PPMS.
abstract: OBJECTIVE
  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.
authors.affiliation: From 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.
authors.forename: Carmen
authors.initials: C
authors.lastname: Tur
authors.affiliation: From 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.
authors.forename: Sreeram
authors.initials: S
authors.lastname: Ramagopalan
authors.affiliation: From 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.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Altmann
authors.affiliation: From 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.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Bodini
authors.affiliation: From 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.
authors.forename: Mara
authors.initials: M
authors.lastname: Cercignani
authors.affiliation: From 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.
authors.forename: Zhaleh
authors.initials: Z
authors.lastname: Khaleeli
authors.affiliation: From 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.
authors.forename: David H
authors.initials: DH
authors.lastname: Miller
authors.affiliation: From 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.
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: From 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. o.ciccarelli@ucl.ac.uk.
authors.forename: Olga
authors.initials: O
authors.lastname: Ciccarelli
mesh_terms: D000328:Adult; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D066128:Gray Matter / Q000473:pathology; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000235:genetics* / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology*; D066127:White Matter / Q000473:pathology
chemical_list: D059811:HLA-DRB1 Chains; C507799:HLA-DRB1*15 antigen