Inflammatory disease in HLA-B27 transgenic rats

Inflammatory disease in HLA-B27 transgenic rats

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 h...

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Published in:Immunological reviews Vol. 169; no. 1; pp. 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: Journal Article
Language:English
Published: Oxford, UK Blackwell Publishing Ltd 01-06-1999
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
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Summary: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.
Bibliography:ark:/67375/WNG-GQQ97SVB-9
istex:AB5E8FB445516DF6B9296450F12D0D66D07C8F21
ArticleID:IMR209
Department of Molecular Medicine, University of Auckland, New Zealand.
University of Texas, Department of Microbiology, Austin, Texas, USA.
Department of Pediatrics, University of Kentucky Medical Center. Lexington, Kentucky, USA.
Antigen Presentation Research Group, Imperial College School of Medicine at Northwick Park Institute for Medical Research, Harrow, Middlesex, UK.
Brooklyn Hospital Center, Brooklyn, New York, USA.
Department of Molecular Biology & Oncology. University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Abou‐Jaoude Hospital, Beirut, Lebanon.
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ISSN:0105-2896
1600-065X
DOI:10.1111/j.1600-065X.1999.tb01317.x