Immunologic Research

, Volume 60, Issue 1, pp 50–59 | Cite as

Increased levels of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atherosclerosis and cardiovascular diseases in patients with mixed connective tissue disease

  • Edit Bodolay
  • Zoltan Prohászka
  • Gyorgy Paragh
  • Istvan Csipő
  • Gabor Nagy
  • Renata Laczik
  • Nora Demeter
  • Eva Zöld
  • Britt Nakken
  • Gyula Szegedi
  • Peter SzodorayEmail author


Heat-shock protein 60 (Hsp60) has been shown to provoke inflammation, and anti-Hsp60 may facilitate the development of atherosclerosis. In this study, we have investigated 30 patients with mixed connective tissue disease (MCTD) and assessed anti-Hsp60 and their relationship to cardiovascular diseases (CVD). Out of 30 patients with MCTD, 15 had CVDs. Anti-Hsp60 antibody was determined by enzyme-linked immunosorbent assay. Since endothelial dysfunction and accelerated atherosclerosis are characteristic to MCTD, a wide array of MCTD-, endothelial dysfunction- and CVD-associated parameters was investigated: serum lipid levels, paraoxonase activity (PON1), rich nuclear ribonucleoprotein U1 (anti-U1RNP), anti-endothelial cell antibodies, anti-cardiolipin and anti-β2-glycoprotein I antibody isotypes (anti-CL and anti-β2GPI), endothelin-1 (ET-1) levels, also intima–media thickness (IMT), a quantitative indicator of atherosclerosis. In MCTD, anti-Hsp60 antibody levels were significantly higher than in healthy individuals (p < 0.02). MCTD patients with CVD had significantly higher levels of anti-Hsp60 compared to MCTD without CVD (p = 0.001). Patients with MCTD had significantly lower high-density lipoprotein cholesterol (p = 0.02) and PON activity (p < 0.001), and significantly increased systolic (p < 0.0002) and diastolic (p < 0.001) blood pressure compared to healthy individuals. Anti-U1RNP levels (p < 0.002) and IMT were higher in patients compared to controls (p = 0.002). The CVD-positive MCTD patients had increased anti-Hsp60 (p < 0.0013), anti-CL IgG (p = 0.0005), ET-1 serum concentration (p < 0.05) and IMT levels (p < 0.001) compared to MCTD patients without CVD. Anti-Hsp60 showed a strong correlation with anti-oxLDL (r = 0.36, p = 0.01) and serum ET-1 (r = 0.62, p < 0.001) and negative correlation with PON activity (r = −0.47, p = 0.01). Anti-Hsp60 indicates endothelial injury, CVD, and can function as a novel atherosclerotic risk factor, also a valuable diagnostic marker in patients with MCTD.


Mixed connective tissue disease Anti-Hsp60 antibody Dyslipidemia Endothelial dysfunction Atherosclerosis Cardiovascular disease 



Anti-endothelial cell antibodies


Antinuclear antibodies




β2-Glycoprotein I


Body mass index


Blood pressure






Cardiovascular disease


Double-stranded deoxyribonucleic acid




Enzyme-linked immunosorbent assay










High-density lipoprotein


High-sensitivity C-reactive protein


Heat-shock protein


High-resolution CT scanning


Carotid artery intima–media thickness


Low-density lipoprotein


Mixed connective tissue disease


Nonsteroidal anti-inflammatory drugs


Oxidized low-density lipoprotein


Pulmonary arterial hypertension


Paraoxonase activity


Uridine-rich ribonucleoprotein


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Edit Bodolay
    • 1
  • Zoltan Prohászka
    • 2
  • Gyorgy Paragh
    • 3
  • Istvan Csipő
    • 1
  • Gabor Nagy
    • 1
  • Renata Laczik
    • 4
  • Nora Demeter
    • 5
  • Eva Zöld
    • 1
  • Britt Nakken
    • 6
  • Gyula Szegedi
    • 1
  • Peter Szodoray
    • 6
    Email author
  1. 1.Department of Clinical Immunology, Institute of MedicineUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  2. 2.Research Laboratory, 3rd Department of Internal MedicineSemmelweis UniversityBudapestHungary
  3. 3.Division of Metabolic Diseases, Institute of MedicineUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  4. 4.Institute of ImmunologyUniversity of Debrecen Medical and Health Science CenterDebrecenHungary
  5. 5.Department of Radiology, Medical SchoolUniversity of PécsPecsHungary
  6. 6.Institute of Immunology, Rikshospitalet, Oslo University HospitalUniversity of OsloOsloNorway

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