Inflammatory disease in HLA-B27 transgenic rats

Joel D Taurog, Shanna D. Maika, Nimman Satumtira, Martha L. Dorris, Ian Lachlan McLean, Hiromi Yanagisawa, Alain Sayad, Andrew J. Stagg, Graham M. Fox, Ann Le O'Brien, Muhammad Rehman, Ming Zhou, Allison L. Weiner, Judy B. Splawski, James A Richardson, Robert E Hammer

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173 Scopus citations

Abstract

A spontaneous inflammatory disease in rats transgenic for HLA-B27 resembles the B27-associated human spondyloarthropathies. Colitis and arthritis, the two most important features, require T cells, gut bacteria, and high expression of B27 in bone marrow-derived cells. Control rats with HLA-B7 remain healthy. Most rats with HLA-Cw6 (associated with psoriasis vulgaris) remain healthy; a minority develop mild and transient disease. Rats with a mutant B27 with a Cys67→Ser substitution resemble wild-type B27 transgenics, but with a lower prevalence of arthritis. A similar phenotype is seen in B27 rats co-expressing a viral peptide that binds B27. Disease-prone LEW but not F344 B27 rats develop high serum IgA levels concurrent with disease progression. Colitis is associated with high interferon-γ, arthritis with high interleukin-6. Disease is similar in B27 LEW, F344, and PVG rats, but the DA background is protective. Conclusions: The spondyloarthropathy-like disease in rats is specific for HLA-B27 but does not require Cys67. Arthritis but nor colitis is particularly sensitive to B27 peptide-binding specificity. Genetic background exerts a strong influence, but some phenotypic differences exist between permissive strains that do not influence disease susceptibility. The data favor a role for B27 peptide presentation in arthritis, but other mechanisms to explain the role of B27 have not been excluded.

Original languageEnglish (US)
Pages (from-to)209-223
Number of pages15
JournalImmunological Reviews
Volume169
DOIs
StatePublished - Jul 29 1999

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Taurog, J. D., Maika, S. D., Satumtira, N., Dorris, M. L., McLean, I. L., Yanagisawa, H., Sayad, A., Stagg, A. J., Fox, G. M., O'Brien, A. L., Rehman, M., Zhou, M., Weiner, A. L., Splawski, J. B., Richardson, J. A., & Hammer, R. E. (1999). Inflammatory disease in HLA-B27 transgenic rats. Immunological Reviews, 169, 209-223. https://doi.org/10.1111/j.1600-065X.1999.tb01317.x