HLA DRB1*1501 and intrathecal inflammation in multiple sclerosis

Abstract

CD4 T cells are considered to be pivotal in the pathogenesis of multiple sclerosis (MS), and the human leukocyte antigen (HLA) haplotype associated with DRB1*1501 confers susceptibility to MS in patients of Northern European descent. Some previous studies have suggested an association of DRB1*1501 with T‐ and B‐cell reactivity to specific myelin protein peptides, other studies suggested an association with enhanced cytokine production or intrathecal immunoglobulin (Ig) synthesis. In order to further assess the role of DRB1*1501 in the pathogenesis of MS, we studied intrathecal inflammation and T‐cell phenotypes in patients with possible onset symptoms or clinically definite MS. Presence of DRB1*1501 was associated with higher levels of cerebrospinal fluid (CSF) inflammation as assessed by IgG synthesis levels and higher levels of matrix metalloproteinase‐9 activity. DRB1*1501‐positive patients also had a lower percentage of T cells in CSF expressing HLA‐DR without co‐expressing CD25. These findings suggest that enhanced intrathecal inflammation and an altered T‐cell activation status may be of importance in conferring the DRB1*1501‐associated susceptibility to MS.

Key Biomarkers

Symptom Clusters