HLA DRB1*1501 and intrathecal inflammation in multiple sclerosis.
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.
Sellebjerg
F
F
Department of Neurology, University of Copenhagen, Glostrup Hospital, Denmark. sellebjerg@dadlnet.dk
Jensen
J
J
Madsen
H O
HO
Svejgaard
A
A
D000328:Adult; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000276:immunology*; D009186:Myelin Sheath / Q000276:immunology; D009187:Myelitis / Q000276:immunology*; D015375:Receptors, Interleukin-2 / Q000032:analysis; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D015375:Receptors, Interleukin-2