Inflammatory disease in HLA-B27 transgenic rats

• Published in: Immunological reviews 1999-06, Vol.169 (1), p.209-223
• Main Authors: Taugor, Joel D., Maika, Shanna D., Satumtira, Nimman, Dorris, Martha L., McLean, Ian Lochlan, Yanagisawa, Hiromi, Sayad, Alain, Stagg, Andrew J., Fox, Graham M., Le O'Brein, Anne, Rehman, Muhammad, Zhou, Ming, Weiner, Allison L., Splawski, Judy B., Richardson, James A., Hammer, Robert E.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Animals, Genetically Modified; Antigen Presentation; Arthritis - genetics; Arthritis - immunology; Cytokines - immunology; Disease Models, Animal; histocompatibility antigen HLA; HLA-B27 Antigen - genetics; Humans; Immunity, Cellular; Immunoglobulin A - blood; Inflammation - genetics; Inflammation - immunology; Mutation; Peptides - genetics; Peptides - immunology; Phenotype; Rats; Rats, Inbred Strains; Spondylitis - genetics; Spondylitis - immunology
• ISSN: 0105-2896; 1600-065X
• DOI: 10.1111/j.1600-065X.1999.tb01317.x

A spontaneous inflammatory disease in rats transgenic for HLAB27 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 B2 7 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‐y, 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 not 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.