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J Exp Med. Dec 1, 1994; 180(6): 2359–2364.
PMCID: PMC2191772

The germfree state prevents development of gut and joint inflammatory disease in HLA-B27 transgenic rats

Abstract

A number of inflammatory disease states occur with greatly increased frequency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27. In a minority of cases, namely those with B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourinary bacterial pathogen. For the majority of B27-associated disease, no definite pathogenetic role for bacteria has been established. However, in these latter cases intestinal inflammation can often be demonstrated, and it sometimes occupies a major part of the clinical picture. Rats transgenic for B27 are known to develop a disorder resembling B27-associated human disease, with prominent intestinal, joint, skin, and male genital inflammatory lesions. We report here that B27 transgenic rats raised in a germfree environment do not develop inflammatory intestinal or peripheral joint disease, whereas the skin and genital inflammatory lesions are unaffected by the germfree state. These findings support the concept that gut and joint inflammation are pathogenetically closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associated gut and joint inflammation.

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Selected References

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  • Hammer RE, Maika SD, Richardson JA, Tang JP, Taurog JD. Spontaneous inflammatory disease in transgenic rats expressing HLA-B27 and human beta 2m: an animal model of HLA-B27-associated human disorders. Cell. 1990 Nov 30;63(5):1099–1112. [PubMed]
  • Keat A. Reiter's syndrome and reactive arthritis in perspective. N Engl J Med. 1983 Dec 29;309(26):1606–1615. [PubMed]
  • Woodrow JC. Genetic aspects of the spondyloarthropathies. Clin Rheum Dis. 1985 Apr;11(1):1–24. [PubMed]
  • Mielants H, Veys EM, Cuvelier C, De Vos M. Subclinical involvement of the gut in undifferentiated spondylarthropathies. Clin Exp Rheumatol. 1989 Sep-Oct;7(5):499–504. [PubMed]
  • Mielants H, Veys EM, Goemaere S, Cuvelier C, De Vos M. A prospective study of patients with spondyloarthropathy with special reference to HLA-B27 and to gut histology. J Rheumatol. 1993 Aug;20(8):1353–1358. [PubMed]
  • Raybourne RB, Williams KM. Monoclonal antibodies against an HLA-B27-derived peptide react with an epitope present on bacterial proteins. J Immunol. 1990 Oct 15;145(8):2539–2544. [PubMed]
  • Scofield RH, Warren WL, Koelsch G, Harley JB. A hypothesis for the HLA-B27 immune dysregulation in spondyloarthropathy: contributions from enteric organisms, B27 structure, peptides bound by B27, and convergent evolution. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9330–9334. [PMC free article] [PubMed]
  • Kapasi K, Inman RD. HLA-B27 expression modulates gram-negative bacterial invasion into transfected L cells. J Immunol. 1992 Jun 1;148(11):3554–3559. [PubMed]
  • Stimpson SA, Brown RR, Anderle SK, Klapper DG, Clark RL, Cromartie WJ, Schwab JH. Arthropathic properties of cell wall polymers from normal flora bacteria. Infect Immun. 1986 Jan;51(1):240–249. [PMC free article] [PubMed]
  • Taurog JD, Maika SD, Simmons WA, Breban M, Hammer RE. Susceptibility to inflammatory disease in HLA-B27 transgenic rat lines correlates with the level of B27 expression. J Immunol. 1993 May 1;150(9):4168–4178. [PubMed]
  • Baumann H, Maquat LE. Localization of DNA sequences involved in dexamethasone-dependent expression of the rat alpha 1-acid glycoprotein gene. Mol Cell Biol. 1986 Jul;6(7):2551–2561. [PMC free article] [PubMed]
  • Thompson GR, Trexler PC. Gastrointestinal structure and function in germ-free or gnotobiotic animals. Gut. 1971 Mar;12(3):230–235. [PMC free article] [PubMed]
  • Turnley AM, Morahan G, Okano H, Bernard O, Mikoshiba K, Allison J, Bartlett PF, Miller JF. Dysmyelination in transgenic mice resulting from expression of class I histocompatibility molecules in oligodendrocytes. Nature. 1991 Oct 10;353(6344):566–569. [PubMed]
  • Yoshioka T, Feigenbaum L, Jay G. Transgenic mouse model for central nervous system demyelination. Mol Cell Biol. 1991 Nov;11(11):5479–5486. [PMC free article] [PubMed]
  • Sadlack B, Merz H, Schorle H, Schimpl A, Feller AC, Horak I. Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene. Cell. 1993 Oct 22;75(2):253–261. [PubMed]
  • Kirwan J, Edwards A, Huitfeldt B, Thompson P, Currey H. The course of established ankylosing spondylitis and the effects of sulphasalazine over 3 years. Br J Rheumatol. 1993 Aug;32(8):729–733. [PubMed]

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