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Characterization of leucocyte subpopulations in circulating blood of patients with chronic thromboembolic pulmonary hypertension (CTEPH).
Authors : S Voss (Bad Nauheim,DE), C Wiedenroth (Bad Nauheim,DE), L Essmann (Bad Nauheim,DE), C Troidl (Giessen,DE), H Nef (Giessen,DE), O Doerr (Giessen,DE), C Lipps (Giessen,DE), J Hoffmann (Frankfurt am Main,DE), G Aleshcheva (Bad Nauheim,DE), E Mayer (Bad Nauheim,DE), C Hamm (Giessen,DE), C Liebetrau (Bad Nauheim,DE)
S. Voss1
,
C. Wiedenroth2
,
L. Essmann1
,
C. Troidl3
,
H. Nef3
,
O. Doerr3
,
C. Lipps3
,
J. Hoffmann4
,
G. Aleshcheva1
,
E. Mayer2
,
C. Hamm3
,
C. Liebetrau1
,
1Kerckhoff Heart and Thorax Center, Cardiology - Bad Nauheim - Germany
,
2Kerckhoff Heart and Thorax Center, Thoracic Surgery - Bad Nauheim - Germany
,
3Justus-Liebig-University Giessen, Medical Clinic I, Cardiology and Angiology - Giessen - Germany
,
4Goethe University Frankfurt, Medical Clinic III, Cardiology - Frankfurt am Main - Germany
,
Background: Repeated thromboembolic events in pulmonary arteries represent a critical factor for the development of severe CTEPH. Pulmonary thromboendarterectomy is a curative treatment option for CTEPH patients, but for those patients in whom surgery is not possible balloon pulmonary angioplasty (BPA) is an alternative therapy. CTEPH is associated with acute and chronic inflammatory processes; however, the immune response as reflected in the pattern of leucocyte subpopulations in the circulating blood of CTEPH patients has not yet been determined.
Purpose: We investigated the influence of pulmonary artery pressure lowering on the profile of leucocyte subsets in CTEPH patients undergoing BPA.
Methods: A total of 38 CTEPH patients who underwent BPA interventions as a staged procedure were included in this study. Right heart catheterization with blood pressure measurement was performed before and after BPA. Venous blood samples for the analysis of circulating leucocyte subsets were collected before and after BPA treatment. Cell populations were quantified in peripheral blood with polychromatic 7-colour flow cytometry (FCM). Venous blood samples were collected from sixteen healthy individuals who served as controls.
Results: At baseline, CTEPH patients had a markedly elevated mean pulmonary artery pressure (PAPm 41±2 mmHg) accompanied by a normal pulmonary artery wedge pressure (PAWP 10±0.5 mmHg). The PAPm decreased after BPA (34±3 mmHg; p<0.05). The number of lymphocytes was lower in CTEPH patients than in healthy controls (p<0.001). FCM analysis of T cell subsets revealed significantly lower numbers of CD3+ CD4+ T helper cells, CD3+ CD4+ CD8+ circulating T lymphocytes, and regulatory and cytotoxic CD3+ CD8+ T cells as well as a smaller population of natural killer T cells in CTEPH patients than in controls. In contrast, the population of peripheral blood monocytes was increased in CTEPH patients.
Comparison of the levels before and after BPA revealed an increased number of lymphocytes after BPA (1592±92 cells/μl vs. 1732±84 cells/μl, p<0.05) and increased numbers of CD3+ T cells (1175±73 cells/μl vs. 1302±70 cells/μl, p<0.01). In addition, quantitative FCM analysis of T-cell subsets revealed higher numbers of CD3+ CD4+ T helper cells (p<0.05), regulatory/cytotoxic CD3+ CD8+ T cells (p<0.01), and double-negative CD3+ pre-T lymphocytes (p<0.05) after BPA treatment. In contrast, the increased population of peripheral blood monocytes prior to BPA was not affected by BPA treatment (p=0.38).
Conclusion: The remodelling of pulmonary arterial vessels that occurs in CTEPH is known to be associated with an accumulation of inflammatory cells. In this study, we describe a detailed quantification of circulating leucocytes. Our results demonstrate that the altered distribution of leucocyte subsets in the peripheral blood of CTEPH patients, especially the depletion of T lymphocytes, may be ameliorated by the decreased pulmonary artery pressure produced by BPA.
ESC 365 is supported by Bayer, Boehringer Ingelheim and Lilly Alliance, Bristol-Myers Squibb and Pfizer Alliance, Novartis Pharma AG and Vifor Pharma in the form of educational grants. The sponsors were not involved in the development of this platform and had no influence on its content.
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