Inflammatory disease in HLA-B27 transgenic rats

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 expre ssion of B27 in bone marrow-derived cells. Control rats with HLA-B7 remain healthy; Most rats with HLA-Cw6 (associated with. psoriasis vulgaris) remai n healthy; a minority develop mild and transient disease. Rats with a mutan t B27 with a Cys67-->Ser substitution resemble wild-type B27 transgenics, b ut 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 n ot F344 B27 rats develop high serum IgA levels concurrent with disease prog ression. Colitis is associated with high interferon-gamma, arthritis with h igh interleukin-6. Disease is similar in B27 LEW, F344, and PVG rats, but t he DA background is protective. Conclusions: The spondyloarthropathy-like d isease in rats is specific for HLA-B27 but does not require Cys67. Arthriti s but not colitis is particularly sensitive to B27 peptide-binding specific ity. Genetic background exerts a strong influence, but some phenotypic diff erences exist between permissive strains that do not influence disease susc eptibility. The data favor a role for B27 peptide presentation in arthritis , but other mechanisms to explain the role of B27 have not been excluded.