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The presence of glutamic acid at positions 71 or 74 in pocket 4 of the HLA-DRß1 chain is associated with the clinical course of multiple sclerosis
- Publication Year :
- 2005
- Publisher :
- BMJ Group, 2005.
-
Abstract
- 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 beta 1 chain (beta 171 / beta 174). 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 beta 171 / beta 174 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 beta 171 / beta 174 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 beta 171 / beta 174 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 beta 1 chain could influence the clinical course of MS by determining protection against RR/SP-MS or susceptibility to the development of PP-MS.
- Subjects :
- Paper
Genotype
Glutamic Acid
Human leukocyte antigen
Biology
HLA-DR
Humans
Allele
Beta (finance)
HLA-DR Antigen
Alleles
Genetics
chemistry.chemical_classification
Binding Sites
Glutamic acid
HLA-DR Antigens
Multiple Sclerosis, Chronic Progressive
Molecular biology
Amino acid
Psychiatry and Mental health
chemistry
Disease Progression
Surgery
Neurology (clinical)
HLA-DRB1 Chains
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....8edc14e366554a3c444f784d7afc5fc3