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

David S. Bradley, Gerald H. Nabozny, Shen Cheng, Paul Zhou, Marie M. Griffiths, Harvinder S. Luthra, Chella S. David

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76 Scopus citations

Abstract

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

Original languageEnglish (US)
Pages (from-to)2227-2234
Number of pages8
JournalJournal of Clinical Investigation
Volume100
Issue number9
StatePublished - Nov 1 1997

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Keywords

  • Autoimmune disease
  • HLA class II
  • Rheumatoid arthritis
  • Transgenic mice
  • Type II collagen

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Bradley, D. S., Nabozny, G. H., Cheng, S., Zhou, P., Griffiths, M. M., Luthra, H. S., & David, C. S. (1997). HLA-DQB1 polymorphism determines incidence, onset, and severity of collagen-induced arthritis in transgenic mice: Implications in human rheumatoid arthritis. Journal of Clinical Investigation, 100(9), 2227-2234.