THE GERM-FREE STATE PREVENTS DEVELOPMENT OF GUT AND JOINT INFLAMMATORY DISEASE IN HLA-B27 TRANSGENIC RATS

A number of inflammatory disease states occur with greatly increased f requency in individuals inheriting the human major histocompatibility complex class I allele HLA-B27. In a minority of cases, namely those w ith B27-associated reactive arthritis, there is good evidence that the disease state is triggered by infection with an enteric or genitourin ary 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 demonstra ted, and it sometimes occupies a major part of the clinical picture. R ats 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 inte stinal or peripheral joint disease, whereas the skin and genital infla mmatory lesions are unaffected by the germfree state. These findings s upport the concept that gut and joint inflammation are pathogeneticall y closely related, and they provide direct evidence that the commensal gut flora play an important role in the pathogenesis of B27-associate d gut and joint inflammation.