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A Shift in the Balance of Regulatory T and T Helper 17 Cells in Rheumatic Heart Disease
  1. Hatice Duygu Bas, MD*,
  2. Kazim Baser, MD,
  3. Emine Yavuz, PhD,
  4. Hasan Ata Bolayir, MD*,
  5. Belma Yaman, MD*,
  6. Serkan Unlu, MD*,
  7. Atiye Cengel, MD*,
  8. Emin Umit Bagriacik, PhD,
  9. Ridvan Yalcin, MD*
  1. From the *Department of Cardiology, Gazi University Faculty of Medicine; †Cardiology Department, Ankara Turkiye Yuksek Ihtisas Hospital; and ‡Department of Immunology, Immunology Research Center, Gazi University Faculty of Medicine, Ankara, Turkey.
  1. Received June 25, 2013, and in revised form September 24, 2013.
  2. Accepted for publication September 26, 2013.
  3. Reprints: Hatice Duygu Bas, MD, Department of Cardiology, Gazi University Faculty of Medicine, Besevler, 06560, Ankara, Turkey. E-mail: hduygubas{at}
  4. This study was funded by Gazi University Scientific Research Projects fund and Clinical Vascular Biology Society of Turkey.
  5. The authors have no conflicts of interest to declare.


Background Autoimmunity plays an essential role in the pathogenesis of rheumatic heart disease (RHD); however, cellular mechanisms of autoimmune response are unclear. Whereas T helper 17 (TH17) and regulatory T cells (Treg) cells share a common differentiation pathway, they play opposite roles in the immune tolerance and autoimmune diseases. Although high TH17/Treg ratio has been shown in several autoimmune diseases, no data are available in RHD. This study investigated the balance between TH17 and Treg in rheumatic mitral valve disease (MVD).

Methods Forty patients with rheumatic MVD and 23 control subjects were enrolled into the study. All subjects underwent clinical, electrocardiographic, and echocardiographic evaluation. The percentages of circulating TH17 and Treg cells were analyzed by flow cytometry. Serum levels of high-sensitivity C-reactive protein (hs-CRP) and cytokines were assessed by enzyme-linked immunosorbent assay.

Results As compared with control subjects, rheumatic MVD patients showed significant increase in peripheral TH17 percentage, high serum levels of TH17-related cytokine interleukin 17A, and an obvious decrease in the percentage of Treg cells. T helper 17/Treg ratio was significantly high in rheumatic MVD patients compared with control subjects (P = 0.0001). Serum concentrations of hs-CRP in rheumatic MVD group were higher than those of the control subjects, and hs-CRP levels correlated with the TH17/Treg ratio (r = 0.71, P = 0.0001). Serum levels of transforming growth factor β1 were increased in rheumatic MVD group compared with those of the control subjects.

Conclusions The results indicated that high TH17/Treg ratio exists inrheumatic MVD. This imbalance may play a role in the pathogenesis, and TH17/Treg balance may be a promising therapeutic approach in RHD.

Key Words
  • T helper 17 (TH17)
  • regulatory T cells (Treg)
  • TH17/Treg ratio
  • rheumatic heart disease
  • autoimmunity

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