[Recent knowledge and hypotheses on the significance of the HLA-D region in rheumatoid arthritis]

Abstract

Rheumatoid arthritis (RA) may result from an interaction between genetic and environmental factors. There is a well documented association between RA and the serologically defined class II MHC antigen haplotype DR4-DRw53-DQw3. Cellular HLA typing reveals five Dw subtypes (Dw4, 10, 13, 14, 15) of this haplotype. DNA coding for this Dw-subtypes occurs in the third hypervariable region (3. HVR) of the DR beta 1 domain suggesting, that this part of the molecule is recognized by T cells. Relatively circumscribed amino acid changes in this 3. HVR, which contains an alpha-helical structure, may result in immune response changes. Susceptibility to RA may be due to related epitopes found in non-Dw10 subtypes of DR4, as well as in DR1 alleles. Studies, using T cell clones specific for the Dw14 subtype of DR4 found Dw14-associated epitopes in 100% (!) also on non-DR4 haplotypes, in the population with RA. Typing with primed lymphocytes may give rise to the association of HLA and RA.