CTLA-4 expression is a promising biomarker of idiopathic pulmonary arterial hypertension and allows differentiation of the type of pulmonary hypertension


Pulmonary arterial hypertension (PAH) is an increasingly frequently diagnosed disease, the molecular mechanisms of which have not been thoroughly investigated. The aim of our study was to investigate subpopulations of lymphocytes to better understand their role in the molecular pathomechanisms of various types of PAH and to find a suitable biomarker that could be useful in the differential diagnosis of PAH. Using flow cytometry, we measured the frequencies of lymphocyte subpopulations CD4+CTLA-4+, CD8+ CTLA-4+ and CD19+ CTLA-4+ in patients with different types of PAH, namely pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH), pulmonary arterial hypertension associated with connective tissue disorders (CTD-PAH), chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH), and in an age- and sex-matched control group in relation to selected clinical parameters. Patients in the iPAH group had the significantly highest percentage of CD4+CTLA-4+ T lymphocytes among all PAH groups, as compared to those in the control group (p < 0.001), patients with CTEPH (p < 0.001), CTD-PAH (p < 0.001) and CHD-PAH (p < 0.01). In iPAH patients, the percentages of CD4+CTLA-4+ T cells correlated strongly positively with the severity of heart failure New York Heart Association (NYHA) Functional Classification (r = 0.7077, p < 0.001). Moreover, the percentage of B CD19+CTLA-4+ cells strongly positively correlated with the concentration of NT-proBNP (r = 0.8498, p < 0.001). We have shown that statistically significantly higher percentages of CD4+CTLA-4+ (p ≤ 0.01) and CD8+ CTLA-4+ (p ≤ 0.001) T cells, measured at the time of iPAH diagnosis, were found in patients who died within 5 years of the diagnosis, which allows us to consider both of the above lymphocyte subpopulations as a negative prognostic/predictive factor in iPAH. CTLA-4 may be a promising biomarker of noninvasive detection of iPAH, but its role in planning the treatment strategy of PAH remains unclear. Further studies on T and B lymphocyte subsets are needed in different types of PAH to ascertain the relationships that exist between them and the disease.

CTLA-4 expression is a promising biomarker of idiopathic pulmonary arterial hypertension and allows differentiation of the type of pulmonary hypertension
Tomaszewski Michał
Słowa kluczowe
CTLA-4; pulmonary arterial hypertension; lymphocytes
Słowa kluczowe
tętnicze nadciśnienie płucne; limfocyty
Małkowska Paulina ORCID 0000-0003-2430-5020
Sierawska Olga ORCID 0000-0003-3567-7786
Hrynkiewicz Rafał ORCID 0000-0002-0688-6928
Mroczek Ewa
Darocha Szymon
Hymos Anna
Błaszczak Piotr
Grywalska Ewelina
Niedźwiedzka-Rystwej Paulina ORCID 0000-0003-4065-3842
Typ zasobu
Identyfikator zasobu
DOI 10.3390/ijms232415910
International Journal of Molecular Sciences, 2022, vol. 23 iss. 24, [br. s.], 15910
Prawa autorskie
Dyscyplina naukowa
Nauki biologiczne; Dziedzina nauk ścisłych i przyrodniczych
Publikacje pracowników US
Data udostępnienia26 sty 2023, 15:28:39
Data mod.26 sty 2023, 15:28:39
Aktywnych wyświetleń0