Related Experiment Video
Updated: Jan 1, 2026
An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15
Lukas Simon Enz1, Thomas Zeis1, Daniela Schmid1
1From the Neurobiology (L.S.E., T.Z., D.S., N.S.-W.), Department of Biomedicine, University Hospital Basel, University Basel, Zentrum für Lehre und Forschung, Switzerland; Department of Biomedicine (F.G.), Bioinformatics Core Facility, University Hospital Basel, Switzerland; SIB Swiss Institute of Bioinformatics (F.G.), Basel, Switzerland; Institute of Neuropathology (F.v.d.M., C.S.), University Medical Center, Göttingen, Germany; Roche Pharma Research and Early Development (pRED) (G.S., U.C.), Roche Innovation Center Basel, Switzerland; Institute of Clinical Transfusion Medicine (T.M.C.B.), Hospital Braunschweig, Germany; and Neuroimmunology and MS Research (R.M.), Neurology Clinic, University Hospital Zurich, University Zurich, Switzerland.
Objective:
To investigate molecular changes in multiple sclerosis (MS) normal-appearing cortical gray matter (NAGM).
Methods:
We performed a whole-genome gene expression microarray analysis of human brain autopsy tissues from 64 MS NAGM samples and 42 control gray matter samples. We further examined our cases by HLA genotyping and performed immunohistochemical and immunofluorescent analysis of all human brain tissues.
Results:
HLA-DRB1 is the transcript with highest expression in MS NAGM with a bimodal distribution among the examined cases. Genotyping revealed that every case with the MS-associated HLA-DR15 haplotype also shows high HLA-DRB1 expression and also of the tightly linked HLA-DRB5 allele. Quantitative immunohistochemical analysis confirmed the higher expression of HLA-DRB1 in HLA-DRB1*15:01 cases at the protein level. Analysis of gray matter lesion size revealed a significant increase of cortical lesion size in cases with high HLA-DRB1 expression.
Conclusions:
Our data indicate that increased HLA-DRB1 and -DRB5 expression in the brain of patients with MS may be an important factor in how the HLA-DR15 haplotype contributes to MS pathomechanisms in the target organ.
