Reactive arthritis/Reiter's syndrome (ReA/RS) is known to be related to infection with Chlamydia trachomatis, since the disease has often been observed to follow episodes of urethritis. Studies from the investigator's laboratory have demonstrated that a far larger proportion of ReA/RS cases than expected are attributable to this organism. They have further shown that chlamydia are present in synovial tissues in ReA/RS patients, even in those with long disease duration, and that the organism is metabolically active at that site. Our data show that the primary synovial host cell for persistent chlamydial infection is the monocyte/macrophage. Other studies have demonstrated that chlamydial gene expression is aberrant during synovial infection, with transcription of the major outer membrane protein gene (omp1) severely attenuated and that of the strongly antigenic heat shock protein gene (hsp60) at high level. This latter chlamydial protein is probably the cause of the synovial inflammation characteristic of ReA/RS. The ability of chlamydia to persist in synovial tissue and cause disease results from a balanced host-parasite interaction, and it is the purpose of the present application to delineate the molecular dynamics of that interaction. In the studies proposed here, the investigators employ reverse transcription-polymerase chain reaction (RT-PCR) and other assays to define bacterial gene products relating to cell division, energy metabolism and other critical functions, in both synovial biopsy samples from ReA/RS patients and an in vitro tissue culture model system they have developed. Similarly, they use RT-PCR and other standard molecular and cell biological methods to assess production of cytokines and other proinflammatory molecules by synovial tissue in persistent infection, again using materials from both ReA/RS patients and the in vitro model system. In these and other studies, they address biochemical, molecular genetic, and clinical questions regarding the dynamics of persistent synovial infection with C. trachomatis. Results of these studies will provide a significant new understanding of the roles played by both chlamydia and host in the maintenance of inflammatory joint disease. In future research, they will employ results from the present studies to assess therapies designed to reduce bacterial load in the synovium and inflammation in that tissue, using both the in vitro cell culture system and an animal model of reactive arthritis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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Bacteriology and Mycology Subcommittee 2 (BM)
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Tyree, Bernadette
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Wayne State University
Schools of Medicine
United States
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Gérard, Hervé C; Carter, John D; Hudson, Alan P (2013) Chlamydia trachomatis is present and metabolically active during the remitting phase in synovial tissues from patients with chronic Chlamydia-induced reactive arthritis. Am J Med Sci 346:22-5
Carter, John D; Gerard, Herve C; Whittum-Hudson, Judith A et al. (2012) The molecular basis for disease phenotype in chronic Chlamydia-induced arthritis. Int J Clin Rheumtol 7:627-640
Carter, John D; Gérard, Hervé C; Whittum-Hudson, Judith A et al. (2011) Combination antibiotics for the treatment of Chlamydia-induced reactive arthritis: is a cure in sight? Int J Clin Rheumtol 6:333-345
Gerard, Herve C; Stanich, Jessica A; Oszust, Cynthia E et al. (2010) Functional CCR5 receptor protects patients with arthritis from high synovial burden of infecting Chlamydia trachomatis. Am J Med Sci 340:448-51
Gerard, Herve C; Whittum-Hudson, Judith A; Carter, John D et al. (2010) The pathogenic role of Chlamydia in spondyloarthritis. Curr Opin Rheumatol 22:363-7
Gerard, Herve C; Stanich, Jessica A; Whittum-Hudson, Judith A et al. (2010) Patients with Chlamydia-associated arthritis have ocular (trachoma), not genital, serovars of C. trachomatis in synovial tissue. Microb Pathog 48:62-8
Gerard, Herve C; Whittum-Hudson, Judith A; Carter, John D et al. (2009) Molecular biology of infectious agents in chronic arthritis. Rheum Dis Clin North Am 35:1-19
Stanich, Jessica A; Carter, John D; Whittum-Hudson, Judith et al. (2009) Rheumatoid arthritis: Disease or syndrome? Open Access Rheumatol 1:179-192
Mayes, Maureen D; Whittum-Hudson, Judith A; Oszust, Cynthia et al. (2009) Lack of evidence for bacterial infections in skin in patients with systemic sclerosis. Am J Med Sci 337:233-5
Klos, Andreas; Thalmann, Jessica; Peters, Jan et al. (2009) The transcript profile of persistent Chlamydophila (Chlamydia) pneumoniae in vitro depends on the means by which persistence is induced. FEMS Microbiol Lett 291:120-6

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