(Taken from the application): An infectious etiology for reactive arthritis (ReA) has long been suspected since this diseases often follow primary infections of the gastrointestinal, urogenital, and respiratory tracts. While many bacterial species have been associated with the disease, the genital pathogen Chlamydia trachomatis has emerged as a primary agent due to its high prevalence in the population. However, another species of Chlamydia, Chlamydia pneumoniae shows even more widespread prevalence than does C trachomatis. Chlamydia pneumoniae is a pathogen responsible for various respiratory infections and some reports have associated C pneumoniae with heart diseases and even Alzheimer's disease. Importantly, studies from several groups have provided indirect evidence that this organism may be involved in synovial pathogenesis. Preliminary election microscopic (EM) and polymerase chain reaction (PCR) studies of synovia from arthritis patients and asymptomatic patients confirmed the presence of Chlamydia pneumoniae in human synovia. In the present application, we describe studies to confirm and extend our preliminary observations. We will continue our initial screening of the presence of Chlamydia pneumoniae in the synovium of arthritis patients and we will determine whether patients with AD show also synovial Chlamydia pneumoniae with/without joint pathology, at a higher rate than that of standard arthritis patients. The molecular genetic, EM, IH and other laboratory methods required for these studies are already developed or in place in the collaborators' laboratory. The studies proposed in this application will confirm the presence of Chlamydia pneumoniae in the human synovium, and define metabolic characteristics of the organism and host synovial responses to chlamydial infection in addition to th role of APOE in the pathology of C. pneumoniae. Such new information will augment our understanding of the pathogenesis process leading to arthritides.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Small Research Grants (R03)
Project #
5R03AR047186-03
Application #
6534514
Study Section
Special Emphasis Panel (ZAR1-AAA-B (M1))
Program Officer
Tyree, Bernadette
Project Start
2000-09-01
Project End
2004-08-31
Budget Start
2002-09-01
Budget End
2004-08-31
Support Year
3
Fiscal Year
2002
Total Cost
$72,843
Indirect Cost
Name
Wayne State University
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
City
Detroit
State
MI
Country
United States
Zip Code
48202
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; 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
Carter, John D; Gérard, Hervé C; Espinoza, Luis R et al. (2009) Chlamydiae as etiologic agents in chronic undifferentiated spondylarthritis. Arthritis Rheum 60:1311-6
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
Dreses-Werringloer, Ute; Bhuiyan, Mohammad; Zhao, Yinghao et al. (2009) Initial characterization of Chlamydophila (Chlamydia) pneumoniae cultured from the late-onset Alzheimer brain. Int J Med Microbiol 299:187-201
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
Balin, Brian J; Little, C Scott; Hammond, Christine J et al. (2008) Chlamydophila pneumoniae and the etiology of late-onset Alzheimer's disease. J Alzheimers Dis 13:371-80
Gerard, Herve C; Fomicheva, Ekaterina; Whittum-Hudson, Judith A et al. (2008) Apolipoprotein E4 enhances attachment of Chlamydophila (Chlamydia) pneumoniae elementary bodies to host cells. Microb Pathog 44:279-85
Jabs, Douglas A; Prendergast, Robert A; Campbell, Adam L et al. (2007) Autoimmune Th2-mediated dacryoadenitis in MRL/MpJ mice becomes Th1-mediated in IL-4 deficient MRL/MpJ mice. Invest Ophthalmol Vis Sci 48:5624-9
Dreses-Werringloer, Ute; Gerard, Herve C; Whittum-Hudson, Judith A et al. (2006) Chlamydophila (Chlamydia) pneumoniae infection of human astrocytes and microglia in culture displays an active, rather than a persistent, phenotype. Am J Med Sci 332:168-74

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