Key result
Patients with idiopathic pulmonary arterial hypertension had significantly higher percentages of CD4+CTLA-4+ T lymphocytes compared to controls and other PAH types (p<0.001).
Why the study?
The molecular mechanisms of pulmonary arterial hypertension have not been thoroughly investigated, prompting an evaluation of lymphocyte subpopulations to clarify their role and identify biomarkers for differential diagnosis.
Does CTLA-4 expression differentiate types of pulmonary hypertension and correlate with disease severity and prognosis?
Observational
Does CTLA-4 expression differentiate types of pulmonary hypertension and correlate with disease severity and prognosis?
p-value: p=< 0.001
CTLA-4 expression on T cells is significantly elevated in idiopathic PAH, correlates with disease severity, and may serve as a prognostic biomarker for 5-year mortality.
Lymphocyte profiling may support PAH subtyping; leaves open biomarker validation in prospective cohorts.
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.
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Tomaszewski et al. (2022) conducted an observational in Pulmonary arterial hypertension (PAH). Idiopathic pulmonary arterial hypertension (iPAH) vs. Control group and other types of PAH (CTEPH, CTD-PAH, CHD-PAH) was evaluated on Frequencies of lymphocyte subpopulations CD4+CTLA-4+, CD8+ CTLA-4+ and CD19+ CTLA-4+ (p=< 0.001). Patients with idiopathic pulmonary arterial hypertension had significantly higher percentages of CD4+CTLA-4+ T lymphocytes compared to controls and other PAH types (p<0.001).
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