Cardiovascular Disease

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Cardiovascular Disease

Antibody response to chlamydial heat shock protein is strongly associated with acute coronary syndromes

Circulation. 2003 Jun 24;107(24):3015-7. Epub 2003 Jun 9. Related Articles, Links

Comment in:
Circulation. 2003 Jun 24;107(24):e9053-4.

Antibody response to chlamydial heat shock protein 60 is strongly associated with acute coronary syndromes.

Biasucci LM, Liuzzo G, Ciervo A, Petrucca A, Piro M, Angiolillo DJ, Crea F, Cassone A, Maseri A.

Institute of Cardiology, Universita' Cattolica, Roma, Italy. lmbiasucci@virgilio.it

BACKGROUND: Heat shock proteins (HSPs) are a family of proteins with immunogenic and proinflammatory properties. Human and Chlamydia pneumoniae (Cp) HSP60 were found in patients with stable coronary disease. METHODS AND RESULTS: We measured the levels of anti-Cp-HSP60 and anti-Cp immunoglobulin G (IgG) in 179 patients with unstable angina, 40 with acute myocardial infarction, and 40 with stable angina (SA), as well as 100 control subjects. Forty-one patients with acute coronary syndromes (ACS) were also studied at follow-up. We also measured plasma levels of high-sensitivity C-reactive protein (hs-CRP) and troponin T (TnT). Seropositivity to Cp-HSP60 was found in 99% of ACS patients but in only 20% of SA patients and none of the control subjects. Seropositivity to Cp was detected in 67% of ACS patients, 60% of SA patients, and 30% of the control subjects. No differences in Cp-HSP60 IgG and in Cp IgG were observed between patients with myocardial infarction and patients with unstable angina. No correlation was found between Cp-HSP60 IgG, TnT, and hs-CRP or between IgG against Cp and hs-CRP. In ACS patients at follow-up, Cp-HSP60 IgG decreased from 0.88+/-0.25 to 0.45+/-0.14 arbitrary units (P<0.0001), becoming negative in 12 patients. CONCLUSIONS: Seropositivity for Cp-HSP60 appears to be a very sensitive and specific marker of ACS, unrelated to Cp IgG antibody titers or hs-CRP and TnT levels. Its causal involvement in instability and its diagnostic role in ACS deserve further study.

Autoimmunity to heat shock protein 60, CPn infection, and inflammation in predicting coronary risk

Arterioscler Thromb Vasc Biol. 2002 Mar 1;22(3):431-7. Related Articles, Links

Autoimmunityi to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk.

Huittinen T, Leinonen M, Tenkanen L, Manttari M, Virkkunen H, Pitkanen T, Wahlstrom E, Palosuo T, Manninen V, Saikku P.

National Public Health Institute, Oulu, Finland. tiina.huittinen@ktl.fi

Heat shock proteini 60 (Hsp60) and Chlamydia pneumoniae infection have both been associated with cardiovascular diseases. Our aim was to study the role of Hsp60 antibodies as coronary risk predictors and their association with C pneumoniae infection and inflammation. This was a prospective, nested, case-control study. The cases consisted of 239 middle-aged Finnish men who developed myocardial infarction or coronary death during the follow-up. Baseline levels of IgA and IgG antibodies to human-specific and C pneumoniae-specific Hsp60 were measured by enzyme immunoassay. Human Hsp60 IgA, but not IgG or C pneumoniae Hsp60, antibodies were a significant risk factor for coronary events (odds ratio 2.0, 95% CI 1.1 to 3.6, when the fourth and first quartiles are compared). When an elevated human Hsp60 IgA antibody level (above the second quartile) was present simultaneously with a high C pneumoniae IgA antibody level (the third quartile) and an elevated C-reactive protein level (the second quartile), compared with all factors at low levels, the risk was 7.0 (95% CI 2.6 to 19.1) without adjustment and 5.0 (95% CI 1.8 to 14.2) when adjustment was made for age and smoking. In conclusion, an elevated human Hsp60 IgA antibody level was a risk factor for coronary events, especially when it was present together with C pneumoniae infection and inflammation.

Antibodies to Heat Shock Proteins and OMP-A In CAD

Clin Diagn Lab Immunol. 2002 Jan;9(1):66-74.

Antibodies to 60-kilodalton heat shock protein and outer membrane protein 2 of Chlamydia pneumoniae in patients with coronary heart disease.

Ciervo A, Visca P, Petrucca A, Biasucci LM, Maseri A, Cassone A.

Department of Bacteriology and Medical Mycology, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy.

Evidence linking Chlamydia pneumoniae infection to atherosclerosis and to atherothrombotic events has recently emerged. A primary candidate implicated in these pathogenetic events is the 60-kDa chlamydial heat shock protein (HSP60). Another putative candidate to activate a potential proinflammatory mechanism is the chlamydial outer membrane protein 2 (OMP2). We have generated both HSP60 and OMP2 recombinant antigens in a nondenatured form and shown that (i) the two antigens were highly immunogenic in mice and (ii) murine antisera thus generated recognized the native C. pneumoniae proteins. We measured by enzyme linked immunosorbent assay (ELISA) and immunoblot assay antibody titers to the recombinant antigens in samples from 219 patients with coronary heart disease (CHD), 179 patients with unstable angina (UA), 40 patients with acute myocardial infarction (AMI), and 100 age-, sex-, and risk factor-matched healthy controls. We also examined whether anti-HSP60 and/or anti-OMP2 antibodies correlated with anti-C. pneumoniae antibodies assessed by a commercial microimmunofluorescence (MIF) assay. Immunoglobulin G (IgG), but neither IgA nor IgM, antibodies against the two recombinant proteins were detected by ELISA. In particular, anti-HSP60 antibodies were detected in >99% of CHD patients versus 0% of the controls, whereas the proportions of anti-OMP2 positive subjects were >70 and 27%, respectively. Nonetheless, among CHD patients, similar frequencies of positive subjects and titers of anti-HSP60 or anti-OMP2 antibodies were present in UA and AMI subjects. The anti-OMP2, but not the anti-HSP60, antibodies showed high specificity. Consistently, high serological correlation was observed between IgG MIF titers and IgG ELISA reactivity to OMP2 but not to HSP60. Overall, the results of this study demonstrate a strong correlation between CHD and anti-HSP60 IgG levels, as measured by our in-house ELISA. They also suggest that recombinant OMP2 ELISA, because of its high specificity and strong correlation with MIF assay, could be a candidate diagnostic marker for C. pneumoniae infection, which would be of potential usefulness for its specificity and nonsubjective nature.

Influence of CPn infection on aortic stiffness in healthy young men

Influence of Chlamydia pneumoniae infection on aortic stiffness in healthy young men.

Tasaki N, Nakajima M, Yamamoto H, Imazu M, Okimoto T, Otsuka M, Shimizu Y, Kohno N.

Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi Minami-ku, Hiroshima 734-8551, Japan. ntasaki@hiroshima-u.ac.jp

Though Chlamydia pneumoniae infection has been implicated in the pathogenesis of atherosclerosis, its role in early atherogenesis has not been well elucidated. To clarify whether C. pneumoniae infection was related to early atherogenesis, we evaluated the association between serological detection of C. pneumoniae antibodies and aortic stiffness in 102 healthy young male volunteers (mean age 27.1+/-0.4 years). Serum C. pneumoniae IgA and IgG antibodies were measured by the enzyme-linked immunosorbent assay (ELISA). Aortic stiffness was estimated using the brachial-ankle pulse wave velocity (PWV). No significant differences were observed between IgA seropositive and seronegative groups with regard to conventional cardiovascular risk factors. However, the mean PWV value was significantly higher in the IgA seropositive group than the seronegative group. Analyses of subgroups according to C-reactive protein (CRP) level showed that those subjects with IgA seropositivity and a high CRP level (>0.17 mg/l) had the highest PWV values. Multivariate logistic regression analysis revealed that a combination of C. pneumoniae IgA seropositivity and a high CRP level was an independent predictor of high values of PWV. These results suggest that C. pneumoniae infection might contribute to early atherogenesis, which might be associated with chronic inflammation.

CPn infection in patients with diffuse panbronchitis and COPD

Chest. 1998 Oct;114(4):969-71. Related Articles, Links Chlamydia pneumoniae infection in patients with diffuse panbronchiolitis and COPD. Miyashita N, Niki Y, Nakajima M, Kawane H, Matsushima T. Department of Medicine, Kawasaki Medical School, Kurashiki City, Okayama, Japan. STUDY OBJECTIVES: To determine the possible association of Chlamydia pneumoniae infection with diffuse panbronchiolitis (DPB) and with COPD. DESIGN: Prospective case-control study. SETTING: Division of Respiratory Diseasesi, Kawasaki Medical School Hospital. PARTICIPANTS: Fifteen DPB and 77 COPD patients who had acute exacerbations of respiratory conditions and 35 and 120 control subjects, respectively, matched for age, sex, and smoking status. MEASUREMENTS AND RESULTS: Nasopharyngeal swabs and paired serum samples were obtained from all patients and control subjects for isolation and antibody testing of C pneumoniae. C pneumoniae was isolated from one DPB patient and from no COPD patients or control subjects. Serologic evidence of acute C pneumoniae infection was observed in one DPB patient (6.7%) and six COPD patients (7.8%). The prevalence and mean titer of C pneumoniae IgGi and IgA antibodies were significantly higher in COPD patients than in control subjects (p<0.001). However, no such differences were observed between DPB patients and control subjects. CONCLUSIONS: This study showed that C pneumoniae infection may be associated with acute exacerbations of COPD and that chronic C pneumoniae infection is common in COPD but not in DPB.

Chlamydia pneumoniae and Cardiovascular Disease

Chlamydia pneumoniae and Cardiovascular Diseasei Lee Ann Campbell, Cho-Chou Kuo, and J. Thomas Grayston University of Washington, Seattle, Washington, USA http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12887507&dopt=Citation
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