Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology.
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 un...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826274617448202240 |
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| author | DeLuca, G Alterman, R Martin, J Mittal, A Blundell, S Bird, S Beale, H Hong, L Esiri, M |
| author_facet | DeLuca, G Alterman, R Martin, J Mittal, A Blundell, S Bird, S Beale, H Hong, L Esiri, M |
| author_sort | DeLuca, G |
| collection | OXFORD |
| description | 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 cases with multiple sclerosis (n = 108, 34 males) with fresh frozen material available for genetic analyses and fixed material for 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 pathological analyses. For each case, transverse sections from three spinal cord levels (cervical, thoracic and lumbar) were stained for myelin, axons and inflammation. The influence of HLA-DRB1*15 on pathological outcome measures was evaluated. Carriage of HLA-DRB1*15 significantly increased the extent of demyelination (global measure 15+: 23.7% versus 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 = 0.003) 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. |
| first_indexed | 2024-03-06T22:46:10Z |
| format | Journal article |
| id | oxford-uuid:5d40e213-53fb-48e5-94ec-ac41e39eab2b |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:46:10Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:5d40e213-53fb-48e5-94ec-ac41e39eab2b2022-03-26T17:33:13ZCasting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5d40e213-53fb-48e5-94ec-ac41e39eab2bEnglishSymplectic Elements at Oxford2013DeLuca, GAlterman, RMartin, JMittal, ABlundell, SBird, SBeale, HHong, LEsiri, MClinical 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 cases with multiple sclerosis (n = 108, 34 males) with fresh frozen material available for genetic analyses and fixed material for 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 pathological analyses. For each case, transverse sections from three spinal cord levels (cervical, thoracic and lumbar) were stained for myelin, axons and inflammation. The influence of HLA-DRB1*15 on pathological outcome measures was evaluated. Carriage of HLA-DRB1*15 significantly increased the extent of demyelination (global measure 15+: 23.7% versus 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 = 0.003) 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. |
| spellingShingle | DeLuca, G Alterman, R Martin, J Mittal, A Blundell, S Bird, S Beale, H Hong, L Esiri, M Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title | Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title_full | Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title_fullStr | Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title_full_unstemmed | Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title_short | Casting light on multiple sclerosis heterogeneity: the role of HLA-DRB1 on spinal cord pathology. |
| title_sort | casting light on multiple sclerosis heterogeneity the role of hla drb1 on spinal cord pathology |
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