Abstract Details

Title Casting Light on the Heterogeneity of Multiple Sclerosis: The Role of HLA-DRB1 on Spinal Cord Pathology

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 131

Objective

Background BACKGROUND: 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.

Design/Methods DESIGN/METHODS: 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 spinal cord levels (cervical, thoracic and lumbar) were stained for myelin, axons,and inflammation. The influence of HLA-DRB1*15 on pathologic outcome measures was evaluated.

Results RESULTS: Carriage of HLA-DRB1*15 significantly increased the extent of demyelination (global measure: 15+: 23.7% vs. 15-: 12.2%, 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.

Conclusions CONCLUSIONS: 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.

Authors/Disclosures
Gabriele C. De Luca, MD, DPhil, FRCPath, FAAN (University of Oxford) PRESENTER	Dr. De Luca has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Neurology Academy. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. De Luca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. The institution of Dr. De Luca has received research support from NIHR, BRC (Oxford). The institution of Dr. De Luca has received research support from National Health and Medical Research (Australia). The institution of Dr. De Luca has received research support from UK MS Society. The institution of Dr. De Luca has received research support from Oxford-Quinnipiac Partnership. The institution of Dr. De Luca has received research support from US Department of Defense. The institution of Dr. De Luca has received research support from Wellcome ISSF (Oxford). The institution of Dr. De Luca has received research support from Bristol Myers Squibb. The institution of Dr. De Luca has received research support from University of Oxford (John Fell Fund). The institution of Dr. De Luca has received research support from National Health and Medical Research (Australia). Dr. De Luca has a non-compensated relationship as a Editorial board member with MS Journal that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Vice-Chair of Grant Review Panel with UK MS Society that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Steering Group member with MS Academy that is relevant to AAN interests or activities. Dr. De Luca has a non-compensated relationship as a Board of Directors with SEQUINS that is relevant to AAN interests or activities.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file

��ɫ��

��ɫ��