To investigate the impact of rheumatoid arthritis (RA)-associated HLA-DRbeta1 * 0401, * 0402, * 0403, * 0404 and * 0101 subtypes on the protein kinase A (PKA) signaling pathway.
Adenylate cyclase (AC), cAMP and PKA activity in transfectants expressing RA-associated HLA-DRbeta1 subtypes and their mutants were detected.
Compared to HLA-DRbeta1 * 0402 transfectants, the RA-associated HLA-DRbeta1 * 0401, * 0404 and * 0101 transfectants produced significantly lower levels of AC, cAMP and PKA.
RA-associated HLA-DRbeta1 molecules are involved in the pathogenesis of RA through down-regulation of the PKA signaling pathway.