Heat shock protein

A bacterial endotoxin

Repeated Chlamydia pneumonia infection, persistence, caridovascular disease, luteolin

Submitted by Jim K on Wed, 2006-05-31 07:45

I don't believe we have this linked to our Research Pages (Marie?). This is a brilliant dissertation from the Finnish group, some of the world's experts on Cpn as some of the faculty in Helsinki were part of the original group who discovered the very existence of Cpn.

This dissertation demonstrates a number of important findings:

  • Repeated infection with Cpn "...induced persistent chlamydial DNA and inflammation in lung tissue and development of mouse Hsp60 autoantibodies."
  • Repeated infection with Cpn "...significantly increased subendothelial lipid accumulation in the aortic sinus area."
  • That "A flavonoid, luteolin, was shown to effectively decrease the chlamydial load and inflammatory reactions in lung tissue." Note: luteolin is not the same as lutein.
  • Conventional antimicrobial treatments are not effectively to eradicate persistent infection.
Go to the link and you can download the whole thing in pdf form.

Experimental Chlamydia pneumoniae infection model: effects of repeated inoculations and treatment

Liisa Törmäkangas

Lääketieteellinen tiedekunta, Oulun yliopisto

Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between inf

Submitted by mrhodes40 on Mon, 2005-10-17 20:05

Z Kardiol. 2003 Jun;92(6):455-65.

Chlamydial and human heat shock protein 60 homologues in acute coronary syndromes. (Auto-)immune reactions as a link between infection and atherosclerosis

[Article in German]

Andrie R, Braun P, Welsch U, Straube E, Hopp HW, Erdmann E, Luderitz B, Bauriedel G.

Medizinische Klinik und Poliklinik II, Universitatsklinikum Bonn, Sigmund-Freud-Str. 25, 53105 Bonn, Germany.

Recent studies provide evidence that infectious agents play a causal role in the pathogenesis of atherosclerosis. In this respect, a chronic persistent Chlamydia pneumoniae infection, indicated by the presence of chlamydial heat shock protein 60 (cHSP 60), is of central interest. Both cHSP60 and endogenous human (h) HSP60 are upregulated under stress conditions in intimal cells and serve as a target for cross-reactive cytotoxic HSP-serum-antibodies. Therefore, the present study evaluates the expressions of both HSP60 homologues in advanced human coronary lesions and a correlation between intimal tissuebound protein and serum antibodies (Ab) to HSP65. Coronary atherectomy specimens retrieved from 114 primary target lesions of patients with acute coronary syndrome (ACS; n=46) or stable angina (SA; n=68) were assessed immunohistochemically for the presence of cHSP60 and hHSP60. Chronic persistency of Chlamydia pneumoniae was additionally examined by transmission electron microscopy. Blood samples from30 patients were tested for anti-Chlamydia pneumoniae-IgG/IgA- and anti-HSP65-Ab titers and for serum CRP levels. Coronary plaques revealed immunoreactive cHSP60 in 47% and hHSP60 in 57% of the lesions colocalized within macrophages/foam cells. Chlamydia in foam cells most often presented ultrastructural patterns that pointed to the persistency of the pathogen. Intact, non-atherosclerotic vessels showed no signals. Mean expressions were 3.1% for cHSP60 and 3.3% for hHSP60. As a central finding, the expression of both HSP homologues was significantly (each p<0.001) higher in ACS lesions compared to SA lesions (cHSP60: 6.2 vs 1.0%, and hHSP60: 7.2 vs 0.7%). Moreover, we found positive correlations between both determinants in ACS and SA lesions (r=0.41, r=0.37; p<0.01). Most interestingly, cHSP60 revealed no relationship with anti-Chlamydia pneumoniae-IgG/IgA titers, whereas expression of cHSP60 as well as that of hHSP60 correlated with anti-HSP65-Ab titers (r=0.50, p<0.01, and r=0.42, p<0.05, respectively).cHSP60 and hHSP60 colocalize within coronary primary atheroma, most prevalent in lesions associated with ACS. For the first time, our data demonstrate a significant correlation between the intimal expression of these HSP60 homologues and serum HSP65 antibodies, thereby suggesting that humoral immune reactions to bacterial and human HSPs may play an important role in coronary atherosclerosis and plaque instability.

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myoca

Submitted by mrhodes40 on Sun, 2005-10-16 12:55

Atherosclerosis. 2004 Apr;173(2):339-46. Related Articles, Links

Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease.

Heltai K, Kis Z, Burian K, Endresz V, Veres A, Ludwig E, Gonczol E, Valyi-Nagy I.

Department of Cardiology, Railway Hospital, Budapest, Hungary.

The relative significance of traditional risk factors, chronic infections and autoimmune processes in the development of acute myocardial infarction (AMI) has not been fully elucidated. We compared serum IgG antibody titres to various pathogens, i.e. Chlamydia pneumoniae (Cpn), cytomegalovirus (CMV) and herpes simplex virus type 1 (HSV-1), and to the potential autoantigens human heat shock protein 60 (hHSP60) and mycobacterial heat shock protein 65 (mHSP65), in serum samples obtained from patients 3-48 h after AMI (n = 40) or stable effort angina (SEA, n = 43), and from controls (n = 46). The strongest association was observed between AMI and the elevated level of hHSP60 antibodies. The association between AMI and the level of Cpn antibodies was also significant. High levels of hHSP60 and Cpn antibodies represented independent risk factors for the development of AMI, but the simultaneous presence of high levels of antibodies to Cpn and hHSP60 suggested a joint effect on the relative risk of AMI (OR = 12.0-21.1). The antibody titres to mHSP65 were higher in the SEA group than in the controls, and the simultaneous presence of high levels of Cpn and mHSP65 antibodies meant an increased risk among the SEA patients. The antibody titres to CMV or HSV-1 were similar in the three groups. In conclusion, these results demonstrate associations of AMI with high levels of anti-hHSP60 and anti-Cpn antibodies, and of SEA with the level of anti-mHSP65 antibodies, these being independent risk factors.

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

Submitted by mrhodes40 on Sun, 2005-10-16 11:58

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

Submitted by mrhodes40 on Sun, 2005-10-16 11:50

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

Autoimmunity 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 protein 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

Submitted by mrhodes40 on Sun, 2005-10-16 11:39

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.

Reactions to Treatment: Endotoxins, cytokines, porphyria, etc.

Submitted by Jim K on Mon, 2005-08-22 21:09

Bacterial Endotoxin reactions, Cytokine (immune) reactions and inflammation

These are often casually referred to as “herx” reactions, or scientifically as “herxheimer-like” alluding to the Jarisch-Herxheimer reaction to bacterial toxins specifically from syphilis. All gram-negative bacteria, of which Cpn is one, have contain Lipopolysaccharide endotoxin which is released as a matter of course during infection and is partially responsible for the on-going symptoms of the infection. When these bacterial are killed en masse they release larger amounts of endotoxin causing significant symptoms during initial phases of treatment. If the amount of endotoxin exceeds the body's ability to get rid of it, these toxic effects can be life threatening. Even in less threatening amounts, the endotoxins and the resulting reactions can cause oxidative stress and damage to body organs.