Multiple Sclerosis Research Today is a free monthly online journal that collates and summarizes the latest research about Multiple Sclerosis, including details on diagnosis, symptoms, treatment, prognosis.

The presence of glutamic acid at positions 71 or 74 in pocket 4 of the HLA-DRbeta1 chain is associated with the clinical course of multiple sclerosis.

Greer JM, Pender MP

Neuroimmunology Research Centre, Department of Medicine, The University of Queensland, Herston, Queensland 4029, Australia. j.greer@medicine.uq.edu.au

BACKGROUND: Primary progressive multiple sclerosis (PP-MS) differs from relapsing-remitting or secondary progressive MS (RR/SP-MS) in ways suggesting differences in the pathogenic pathways. Susceptibility to both PP-MS and RR/SP-MS is linked to carriage of the HLA molecule DRB1*1501. Several serologically defined HLA-DR groups (DR1, DR4, DR6, and DR9) occur less often in RR/SP-MS than in controls. Some or all of the HLA-DR molecules encoded by alleles in these serologically defined groups have a negatively charged glutamic acid at residue 71 or 74 of the beta1 chain (beta1(71)/beta1(74)). Residues at these positions are important in the formation of pocket 4 in the antigen binding site of the HLA-DR molecule. OBJECTIVES: To investigate whether the presence of alleles encoding HLA-DR molecules containing glutamic acid at beta1(71)/beta1(74) correlates with the course of MS. METHODS: HLA-DR and HLA-DQ alleles and genotypes were analysed in 121 MS patients (50 with PP-MS) and 109 controls by molecular typing. RESULTS: Alleles encoding HLA-DR molecules containing a glutamic acid at beta1(71)/beta1(74) occurred less often in patients with RR/SP-MS than in those with PP-MS or controls. In subjects not carrying the DRB1*1501 allele, a much higher proportion of PP-MS patients carried alleles encoding HLA-DR molecules containing a glutamic acid at beta1(71)/beta1(74) than did RR/SP-MS patients or controls. CONCLUSIONS: The amino acid residues involved in determining the shape and charge of pocket 4 of the HLA-DR beta1 chain could influence the clinical course of MS by determining protection against RR/SP-MS or susceptibility to the development of PP-MS.

Published 18 April 2005 in J Neurol Neurosurg Psychiatry, 76(5): 656-62.
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