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Clinical heterogeneity in multiple sclerosis is the rule. Evidence suggests that HLA-DRB1*15 may play a role in clinical outcome. Spinal cord pathology is common and contributes significantly to disability in the disease. The influence of HLA-DRB1*15 on multiple sclerosis spinal cord pathology is unknown. A post-mortem cohort of pathologically confirmed multiple sclerosis cases (n=108, 34 males) with fresh frozen material available on which to do genetic analyses and fixed material on which to do pathology was used. HLA-DRB1 alleles were genotyped to select a subset of age- and sex-matched HLA-DRB1*15 positive (n=21) and negative (n=26) cases for detailed pathologic analyses. For each case, transverse sections from 3 SC levels (cervical, thoracic and lumbar) were stained for myelin, axons, and inflammation. The influence of HLA-DRB1*15 on pathologic outcome measures was evaluated. Carriage of HLA-DRB1*15 significantly increased the extent of demyelination (global measure: 15+: 23.7% vs. 15-: 12.16%, p=0.004), parenchymal (cervical, p<0.01; thoracic, p<0.05); lumbar, p<0.01) and lesional inflammation (border, p=0.001; periplaque white matter, p<0.05) in the multiple sclerosis spinal cord. HLA-DRB1*15 influenced demyelination through controlling the extent of parenchymal inflammation. Meningeal inflammation correlated significantly with small fibre axonal loss in the lumbar spinal cord (r=-0.832, p<0.001) only in HLA-DRB1*15 positive cases. HLA-DRB1*15 significantly influences pathology in the multiple sclerosis spinal cord. This study casts light on the role of HLA-DRB1*15 in disease outcome and highlights the powerful approach of using microscopic pathology to clarify the way in which genes and clinical phenotypes of neurological diseases are linked.

Type

Journal article

Journal

Brain

Publication Date

2013

Keywords

multiple sclerosis, spinal cord, genetics, pathology, outcome