HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice. Implications in human rheumatoid arthritis.

摘要: Certain HLA-DR alleles have been associated with predisposition to human rheumatoid arthritis (RA). There is also evidence that certain HLA-DQ may be important in determining susceptibility RA. We previously demonstrated mice transgenic for HLA-DQ8, a DQ allele RA, develop severe after type II collagen immunization. To investigate the influence of polymorphic difference at loci on arthritis, we generated HLA-DQ6, an nonsusceptible haplotype. The DQ6 were found resistant collagen-induced arthritis. assessed combined effect RA-susceptible and RA nonassociated by producing double-transgenic expressing DQ8 molecules, representing more prevalent condition humans where heterozygosity common. developed moderate CIA when immunized CII compared observed mice, much like patients bearing both susceptible HLA haplotypes. These studies support role polymorphism