HLA DRB1*1501 and intrathecal inflammation in multiple sclerosis

CD4 T cells are considered to be pivotal in the pathogenesis of multiple sc lerosis (MS), and the human leultocyte antigen (HLA) haplotype associated w ith 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 st udies suggested an association with enhanced cytokine production or intrath ecal immunoglobulin (Ig) synthesis. In order to further assess the role of DRB1*1501 in the pathogenesis of MS, we studied intrathecal inflammation an d T-cell phenotypes in patients with possible onset symptoms or clinically definite MS. Presence of DRB1*1501 was associated with higher levels of cer ebrospinal fluid (CSF) inflammation as assessed by IgG synthesis levels and higher levels of matrix metalloproteinase-9 activity. DRB1*1501-positive p atients also had a lower percentage of T cells in CSF expressing HLA-DR wit hout co-expressing CD25. These findings suggest that enhanced intrathecal i nflammation and an altered T-cell activation status may be of importance in conferring the DRB1*1501-associated susceptibility to MS.