Objective
MICROBIOLOGICAL ASPECTS OF NATURALLY OCCURING JOINT DISEASE A naturally occuring ankylosing enthesopathy (ANKENT) of ankle and tarsal joints was recently described in mice (Folia Biol.,1993; Human Immunol.,1994 In Press).
ANKENT occurs in young adult males. After a short inflammatory period, degenerative changes occur which resemble human seronegative spondylarthritic pathology. The prevalence of the disease in 3- to 10-months-old males is 10-40%. Major histocompatibility antigens (MHC) of the mouse (H-2) and of humans (HLA) are relative risk factors; the role of HLA has been studied using transgenic mice.
Notably, HLA-B27 transgenic mice of the H-2k haplotype have a significantly higher disease frequency than non-transgenic H-2b congenic males. Taken together, ANKENT appears as an excellent model for human B27-associated seronegative joint disease.
The major problem for understanding the pathogenesis of the disease and role of the genetic factor(s) is the stochastic occurence of ANKENT among genetically identical individuals. Evidently, alongside genetic factors, environmental elements must play a role. In analogy to the human B27 associated joint disease, reactive arthritis, along with several animal models, it appears that micro-organisms might be an important factor. So far it has not been possible to identify a particular micro-organism associated with ANKENT.
In this project we propose to approach this question in a new way, by studying the incidence of ANKENT under germ free and gnotobiotic circumstances (e.in the presence of a limited number of well-defined micro-organisms). Hence, mice with the susceptible genotypes would be reared and maintained under germ free or control (conventional) conditions for a period of 10 months.
We are confident that the results will lead to experiments with the aim of identifying arthritogenic peptides, and with perspectives for peptide-vaccine therapy.
Germ-free and gnotobiological facilities at the Czech Academy of Sciences offer a unique possibility for this work.
By participating in the EC Network "Chronic Arthritis", the germ free facilities will also become accessible to other participants of this research network.
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Coordinator
2300 RC Leiden
Netherlands
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