HLA-DRB1∗15 influences the development of brain tissue damage in early PPMS

Carmen Tur, Sreeram Ramagopalan, Daniel R. Altmann, Benedetta Bodini, Mara Cercignani, Zhaleh Khaleeli, David H. Miller, Alan J. Thompson, Olga Ciccarelli

Research output: Contribution to journalArticlepeer-review

Abstract

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 5 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 5 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.

Original languageEnglish
Pages (from-to)1712-1718
Number of pages7
JournalNeurology
Volume83
Issue number19
Publication statusPublished - Nov 1 2014

ASJC Scopus subject areas

  • Clinical Neurology
  • Medicine(all)

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