Skip to main content
SpringerLink
Log in

Impact of seropositivity to Chlamydia pneumoniae and anti-hHSP60 on cardiovascular events in hemodialysis patients

  • Original Paper
  • Published:
Cell Stress and Chaperones Aims and scope

Abstract

Autoimmunity to heat shock protein 60 (HSP60) has been related to atherosclerosis. Chlamydia pneumoniae (CP), the most studied infectious agent implicated in promoting atherosclerosis, produces a form of HSP60, which can induce an autoimmune response, due to high antigenic homology with human HSP60 (hHSP60). In this study, we evaluated the correlations among anti-hHSP60 antibodies, CP infection, and cardiovascular disease (CVD) in a high-risk population, such as patients undergoing hemodialysis (HD). Thirty-two patients (67.9 ± 13.9 years; male/female, 23:9) on regular HD were enrolled. Global absolute cardiovascular risk (GCR) was assessed using the Italian CUORE Project’s risk charts, which evaluate age, gender, smoking habits, diabetes, systolic blood pressure, and serum cholesterol. The occurrence of cardiovascular events during a 24-month follow-up was recorded. Seropositivity to CP and the presence of anti-hHSP60 antibodies were tested by specific enzyme-linked immunosorbent assays. Inflammation was assessed by measurement of C-reactive protein (CRP) serum levels. Fifteen healthy sex and age-matched (61.9 ± 9.5 years; male/female, 11:4) subjects were the control group. Fifteen of 32 patients resulted seropositive for CP. CP + patients were older than CP−, while they did not differ for GCR, CRP, and dialytic parameters. CVD incidence was significantly higher in CP+ (9 CP+ vs 2 CP−, p < 0.05). Cox analysis recognized that the incidence of CVD was independently correlated with seropositivity to CP (HR, 7.59; p = 0.01; 95% CI = 1.63–35.4). On the other hand, there were no significant differences in anti-hHSP60 levels among CP+, CP− and healthy subjects: 18.11 μg/mL (14.8–47.8), 31.4 μg/mL (23.2–75.3), and 24.72 μg/mL (17.7–41.1), respectively. Anti-hHSP60 did not correlate to GCR, CRP, and incidence of CVD. In conclusion, our data suggest that anti-hHSP60 autoimmune response is not related to CP infection and CP-related CVD risk in HD patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Borel N, Summersgill JT, Mukhopadhyay S, Miller RD, Ramirez JA, Pospischil A (2008) Evidence for persistent Chlamydia pneumoniae infection of human coronary atheromas. Atherosclerosis 199(1):154–161

    Article  CAS  PubMed  Google Scholar 

  • Cohen G, Haag-Weber M, Hörl WH (1997) Immune dysfunction in uremia. Kidney Int Suppl 62:S79–S82

    CAS  PubMed  Google Scholar 

  • Deniset JF, Cheung PK, Dibrov E, Lee K, Steigerwald S, Pierce GN (2010) Chlamydophila pneumoniae infection leads to smooth muscle cell proliferation and thickening in the coronary artery without contributions from a host immune response. Am J Pathol 176(2):1028–1037

    Article  CAS  PubMed  Google Scholar 

  • Dieudé M, Gillis MA, Théorêt JF, Thorin E, Lajoie G, Levine JS, Merhi Y, Rauch J (2009) Autoantibodies to heat shock protein 60 promote thrombus formation in a murine model of arterial thrombosis. J Thromb Haemost 7(4):710–719

    Article  PubMed  Google Scholar 

  • Eleftheriadis T, Antoniadi G, Liakopoulos V, Kartsios C, Stefanidis I (2007) Disturbances of acquired immunity in hemodialysis patients. Semin Dial 20:440–451

    Article  PubMed  Google Scholar 

  • Esposito P, Libetta C, Rampino T, Gregorini M, Gabanti E, Portalupi V, Dal Canton A (2010) Autoimmune response to heat shock protein 60 in haemodialysis patients. J Intern Med 267(4):440

    Article  CAS  PubMed  Google Scholar 

  • Ferrario M, Chiodini P, Chambless LE et al (2005) Prediction of coronary events in a low incidence population. Assessing accuracy of the CUORE cohort study prediction equation. Int J Epidemiol 34:413–421

    Article  PubMed  Google Scholar 

  • Foley RN, Parfrey PS, Sarnak MJ (1998) Clinical epidemiology of cardiovascular disease in chronic renal disease. Am J Kidney Dis 32:S112–S119

    Article  CAS  PubMed  Google Scholar 

  • Gattone M, Iacoviello L, Colombo M et al (2001) Chlamydia pneumoniae and cytomegalovirus seropositivity, inflammatory markers, and the risk of myocardial infarction at a young age. Am Heart J 142(4):633–640

    Article  CAS  PubMed  Google Scholar 

  • Gruden G, Bruno G, Chaturvedi N et al (2009) Anti-HSP60 and anti-HSP70 antibody levels and micro⁄macrovascular complications in type 1 diabetes: the EURODIAB. J Intern Med 266(6):527–536

    Article  CAS  PubMed  Google Scholar 

  • Heltai K, Kis Z, Burian K, Endresz V, Veres A, Ludwig E, Gönczöl E, Valyi-Nagy I (2004) Elevated antibody levels against Chlamydia pneumoniae, human HSP60 and mycobacterial HSP65 are independent risk factors in myocardial infarction and ischaemic heart disease. Atherosclerosis 173(2):339–346

    Article  CAS  PubMed  Google Scholar 

  • Högdahl M, Söderlund G, Kihlström E (2008) Expression of chemokines and adhesion molecules in human coronary artery endothelial cells infected with Chlamydia (Chlamydophila) pneumoniae. APMIS 116(12):1082–1088

    Article  PubMed  Google Scholar 

  • Hoshida S, Nishino M, Tanouchi J, Kishimoto T, Yamada Y (2005) Acute Chlamydia pneumoniae infection with heat-shock-protein-60-related response in patients with acute coronary syndrome. Atherosclerosis 183(1):109–12

    Google Scholar 

  • Hoymans VY, Bosmans JM, Van Herck PL, Ieven MM, Vrints CJ (2008) Implications of antibodies to heat-shock proteins in ischemic heart disease. Int J Cardiol 123(3):277–282

    Article  PubMed  Google Scholar 

  • Huittinen T, Leinonen M, Tenkanen L, Mänttäri M, Virkkunen H, Pitkänen T, Wahlström E, Palosuo T, Manninen V, Saikku P (2002) Autoimmunity to human heat shock protein 60, Chlamydia pneumoniae infection, and inflammation in predicting coronary risk. Arterioscler Thromb Vasc Biol 22(3):431–437

    Article  CAS  PubMed  Google Scholar 

  • Ieven MM, Hoymans VY (2005) Involvement of Chlamydia pneumoniae in atherosclerosis: more evidence for lack of evidence. J Clin Microbiol 43(1):19–24

    Article  PubMed  Google Scholar 

  • Kato A, Takita T, Maruyama Y, Hishida A (2004) Chlamydial infection and progression of carotid atherosclerosis in patients on regular haemodialysis. Nephrol Dial Transplant 19(10):2539–2546

    Article  PubMed  Google Scholar 

  • Kato A, Takita T, Furuhashi M, Maruyama Y, Hishida A (2006) Association between seroprevalence of anti-chlamydial antibodies and long-term cardiovascular mortality in chronic hemodialysis patients. Atherosclerosis 188(1):120–125

    Article  CAS  PubMed  Google Scholar 

  • Kendrick J, Chonchol MB (2008) Nontraditional risk factors for cardiovascular disease in patients with chronic kidney disease. Nat Clin Pract Nephrol 4(12):672–681

    Article  PubMed  Google Scholar 

  • Kern JM, Maass V, Maass M (2009) Chlamydia pneumoniae adversely modulates vascular cell properties by direct interaction with signalling cascades. Thromb Haemost 102(6):1064–1070

    CAS  PubMed  Google Scholar 

  • Kim DK, Kim HJ, Han SH, Lee JE, Moon SJ, Kim BS, Kang SW, Choi KH, Lee HY, Han DS (2008) Chlamydia pneumoniae accompanied by inflammation is associated with the progression of atherosclerosis in CAPD patients: a prospective study for 3 years. Nephrol Dial Transplant 23(3):1011–1018

    Article  PubMed  Google Scholar 

  • Lentine KL, Parsonnet J, Taylor I, Wrone EM, Lafayette RA (2006) Associations of serologic markers of infection and inflammation with vascular disease events and mortality in American dialysis patients. Clin Exp Nephrol 10(1):55–62

    Article  CAS  PubMed  Google Scholar 

  • Libetta C, Zucchi M, Gori E, Sepe V, Galli F, Meloni F, Milanesi F, Canton D (2004) Vitamin E-loaded dialyzer resets PBMC-operated cytokine network in dialisi patients. Kidney Int 65(4):1473–1481

    Article  CAS  PubMed  Google Scholar 

  • Lim WH, Kireta S, Leedham E, Russ GR, Coates PT (2007) Uremia impairs monocyte and monocyte-derived dendritic cell function in hemodialysis patients. Kidney Int 72:1138–1148

    Article  CAS  PubMed  Google Scholar 

  • Mitusch R, Luedemann J, Wood WG, Berger K, Schminke U, Suter M, Kessler C, John U, Rupp J, Kentsch M, Maass M (2005) Asymptomatic carotid atherosclerosis is associated with circulating Chlamydia pneumoniae DNA in younger normotensive subjects in a general population survey. Arterioscler Thromb Vasc Biol 25(2):386–391

    Article  CAS  PubMed  Google Scholar 

  • Molestina RE, Miller RD, Ramirez JA, Summersgill JT (1999) Infection of human endothelial cells with Chlamydia pneumoniae stimulates transendothelial migration of neutrophils and monocytes. Infect Immun 67(3):1323–1330

    CAS  PubMed  Google Scholar 

  • Musial K, Szprynger K, Szczepańska M, Zwolińska D (2009) Heat shock proteins in children and young adults on chronic hemodialysis. Pediatr Nephrol 24(10):2029–2034

    Article  PubMed  Google Scholar 

  • Netea MG, Selzman CH, Kullberg BJ, Galama JM, Weinberg A, Stalenhoef AF, Van der Meer JW, Dinarello CA (2000) Acellular components of Chlamydia pneumoniae stimulate cytokine production in human blood mononuclear cells. Eur J Immunol 30(2):541–549

    Article  CAS  PubMed  Google Scholar 

  • O’Connor CM, Dunne MW, Pfeffer MA, Muhlestein JB, Yao L, Gupta S, Benner RJ, Fisher MR, Cook TD; Investigators in the WIZARD Study (2003) Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial. JAMA 17; 290(11):1459–1466

    Google Scholar 

  • Paldanius M, Leinonen M, Virkkunen H, Tenkanen L, Sävykoski T, Mänttäri M, Saikku P (2006) Chlamydia pneumoniae antibody levels before coronary events in the Helsinki heart study as measured by different methods. Diagn Microbiol Infect Dis 56(3):233–239

    Article  CAS  PubMed  Google Scholar 

  • Pesonen E, Andsberg E, Ohlin H, Puolakkainen M, Rautelin H, Sarna S, Persson K (2007) Dual role of infections as risk factors for coronary heart disease. Atherosclerosis 192(2):370–375

    Article  CAS  PubMed  Google Scholar 

  • Sardenberg C, Suassuna P, Andreoli MC, Watanabe R, Dalboni MA, Manfredi SR, dos Santos OP, Kallas EG, Draibe SA, Cendoroglo M (2006) Effects of uraemia and dialysis modality on polymorphonuclear cell apoptosis and function. Nephrol Dial Transplant 21:160–165

    Article  PubMed  Google Scholar 

  • Schett G, Metzler B, Mayr M, Amberger A, Niederwieser D, Gupta RS, Mizzen L, Xu Q, Wick G (1997) Macrophage-lysis mediated by autoantibodies to heat shock protein 65/60. Atherosclerosis 128(1):27–38

    Article  CAS  PubMed  Google Scholar 

  • Soltys BJ, Gupta RS (1997) Cell surface localization of the 60 kDa heat shock caperonin protein (hsp60) in mammalian cells. Cell Biol Int 21(5):315–320

    Article  CAS  PubMed  Google Scholar 

  • Stenvinkel P, Heimburger O, Jogestrand T (2002) Elevated interleukin-6 predicts progressive carotid artery atherosclerosis in dialysis patients: association with Chlamydia pneumoniae seropositivity. Am J Kidney Dis 39(2):274–278

    Article  CAS  PubMed  Google Scholar 

  • Summersgill JT, Molestina RE, Miller RD, Ramirez JA (2000) Interactions of Chlamydia pneumoniae with human endothelial cells. J Infect Dis 181(Suppl 3):S479–S482

    Article  CAS  PubMed  Google Scholar 

  • Tsirpanlis G, Chatzipanagiotou S, Ioannidis A, Ifanti K, Bagos P, Lagouranis A, Poulopoulou C, Nicolaou C (2003) The effect of viable Chlamydia pneumoniae on serum cytokines and adhesion molecules in hemodialysis patients. Kidney Int Suppl 84:S72–S75

    Article  CAS  PubMed  Google Scholar 

  • Watson C, Alp NJ (2008) Role of Chlamydia pneumoniae in atherosclerosis. Clin Sci (Lond) 114(8):509–531

    Article  CAS  Google Scholar 

  • Wszola M, Kwiatkowski A, Nosek R et al (2006) Chlamydia pneumoniae infection and ischemic heart disease in hemodialysis patients. Transplant Proc 38(1):31–34

    Article  CAS  PubMed  Google Scholar 

  • Xu Q (2003) Infections, heat shock proteins, and atherosclerosis. Curr Opin Cardiol 18(4):245–252

    Article  PubMed  Google Scholar 

  • Zoccali C, Mallamaci F, Tripepi G, Parlongo S, Cutrupi S, Benedetto FA, Bonanno G, Seminara G, Fatuzzo P, Rapisarda F, Malatino LS (2003) Chlamydia pneumoniae, overall and cardiovascular mortality in end-stage renal disease (ESRD). Kidney Int 64(2):579–584

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Nephrology, Dialysis and Transplantation Unit, Fondazione IRCCS Policlinico “San Matteo” and Univeristy of Pavia, P.le Golgi, no. 2, 27100, Pavia, Italy

    Pasquale Esposito, Carmelo Libetta, Elisa Gabanti, Teresa Rampino & Antonio Dal Canton

  2. Clinical Epidemiology and Biometric Unit, Fondazione IRCCS Policlinico “San Matteo” and Univeristy of Pavia, Pavia, Italy

    Carmine Tinelli

Authors
  1. Pasquale Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Carmine Tinelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carmelo Libetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elisa Gabanti
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Teresa Rampino
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Dal Canton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Pasquale Esposito.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esposito, P., Tinelli, C., Libetta, C. et al. Impact of seropositivity to Chlamydia pneumoniae and anti-hHSP60 on cardiovascular events in hemodialysis patients. Cell Stress and Chaperones 16, 219–224 (2011). https://doi.org/10.1007/s12192-010-0235-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12192-010-0235-5

Keywords

Search

Navigation