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M.V. Kalayoglu, A.M. Lane, E.S. Gragoudas, O.S. Mahdi, G.I. Byrne, J.W. Miller; Association Between Chlamydial Heat Shock Protein 60 and Age–related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2005;46(13):2999.
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Purpose: Increasing evidence suggests that chronic inflammation contributes to the pathogenesis of Age–related Macular Degeneration (AMD). Infection with the prokaryotic pathogen Chlamydia pneumoniae has been associated with AMD by seroepidemiology. In addition, we have detected C. pneumoniae DNA and chlamydial major outer membrane protein within AMD choroidal neovascular membranes (CNV). Since the pathogenesis of C. pneumoniae infection is mediated in large part by chlamydial heat shock protein 60 (cHsp60), this study examined if cHsp60 is associated with AMD. Methods: Sera from 70 consecutive individuals without AMD, 43 patients with dry AMD, 51 patients with neovascular AMD and 49 patients without AMD but with ocular melanoma were collected and assayed for the presence of C–reactive protein (CRP) or IgG antibody to C. pneumoniae elementary bodies, cHsp60, or E. coli Hsp60. An association between AMD and chlamydial infection was evaluated by multivariate logistic regression, controlling for potential confounding variables such as coronary artery disease (history of angina, myocardial infarction, angioplasty or coronary artery bypass grafting), smoking, hypertension and hypercholesterolemia. We evaluated cHsp60 levels (O.D. readings) in all control patients (defined as subjects without AMD), ocular melanoma patients, and all AMD patients. Subgroup analyses were also performed comparing cHsp60 in subjects without AMD (no retinal pathology) to patients with dry AMD or neovascular AMD. Results: Median cHsp60 levels were .53 for subjects without AMD, and .82, .64 and .73 for patients with dry AMD, neovascular AMD, and ocular melanoma, respectively. In multivariate logistic regression models, cHsp60 levels were not statistically significantly associated with AMD (OR: 1.9, 95% CI: 0.95–3.70, P = 0.07). In subgroup analysis, increasing levels of cHsp60 IgG were associated with an increased risk of dry AMD (OR: 3.7, 95% CI: 1.003–14.0, P = 0.049) but not neovascular AMD (OR: 2.1, 95% CI: 0.64–6.90, P = 0.22). CRP, IgG to whole elementary bodies, and IgG to E. coli Hsp60 were not associated with AMD. Conclusions: cHsp60 IgG is associated with dry but not neovascular AMD, suggesting that cHsp60 may be expressed at different stages of inflammation in AMD. If additional studies continue to support a role for C. pneumoniae infection in AMD, then the pathogen may emerge as a novel risk factor for this disease.
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