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

Tur, Carmen, Ramagopalan, Sreeram, Altmann, Daniel R., Bodini, Benedetta, Cercignani, Mara ORCID: https://orcid.org/0000-0002-4550-2456, Khaleeli, Zhaleh, Miller, David H., Thompson, Alan J. and Ciccarelli, Olga 2014. HLA-DRB1*15 influences the development of brain tissue damage in early PPMS. Neurology 83 (19) , pp. 1712-1718. 10.1212/wnl.0000000000000959

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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 = 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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Psychology Cardiff University Brain Research Imaging Centre (CUBRIC)
Publisher:	American Academy of Neurology
ISSN:	0028-3878
Date of Acceptance:	5 August 2014
Last Modified:	09 Nov 2022 10:27
URI:	https://orca.cardiff.ac.uk/id/eprint/139528

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