Inflammatory disease in HLA-B27 transgenic rats

Immunol Rev. 1999 Jun;169:209-23. doi: 10.1111/j.1600-065x.1999.tb01317.x.

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-gamma, 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.

Publication types

  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Antigen Presentation
  • Arthritis / genetics
  • Arthritis / immunology
  • Cytokines / immunology
  • Disease Models, Animal
  • 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

Substances

  • Cytokines
  • HLA-B27 Antigen
  • Immunoglobulin A
  • Peptides