[The suppressive effect of HLA-DQw6 genes on collagen-induced arthritis in mice]

We investigated the effect of HLA-DQw6 genes on collagen-induced arthritis (CIA) in mice, based on our previous observation that the frequency of HLA-DR4-Dw15-DQw4 haplotype was increased in the patients with rheumatoid arthritis (RA) in the Japanese whereas the frequency of HLA-DR2-Dw12-DQw6 was decreased in them significantly. We utilized the HLA-DQw6 genes of transgenic C57BL/6 mice (DQw6-B6) and their F1 progenies with or without DQw6 genes derived from the matings between DBA/1 mice and HLA-DQw6 hemizygous transgenic DQw6-B6 mice. Mice were immunized with bovine type II collagen (C II) followed by boost immunization 3 weeks later. The development of arthritis was observed and the levels of IgG specific to C II were evaluated on ELISA every week until 10 weeks after the first immunization. The incidence of arthritic mice in DQw6(+)-F1 decreased significantly (P less than 0.05) as compared with that in DQw6(-)-F1 42.9% vs. 80.0%). The incidence of arthritic limbs in DQw6(+)-F1 decreased significantly (P less than 0.01) as compared with that in DQw6(-)-F1 (30.2% vs. 58.3%). The level of IgG specific to C II on the 5th week in DQw6(+)-F1 decreased significantly (P less than 0.01) as compared with that in DQw6(-)-F1 (218.6 +/- 39.2 micrograms/ml, mean +/- SEM, n = 21 vs. 431.3 +/- 58.8 micrograms/ml, mean +/- SEM, n = 20). Thus these results suggested that HLA-DQw6 genes suppressed the development of CIA most likely due to the reduction of the production of IgG specific to type II collagen.