Lymphocyte Involvement in the Pathology of Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a disease characterized by increased pulmonary vascular resistance and right heart failure, with emerging evidence suggesting a key role for immune dysregulation in its pathogenesis. This study aimed to assess the involvement of lymphocytes, particularly regulatory T cells (Tregs), and the expression of immune checkpoint molecules PD-1 and PD-L1 on peripheral blood subpopulations in patients diagnosed with PAH. The study involved 25 patients; peripheral blood mononuclear cells were isolated and subsequently analyzed using flow cytometry to quantify the Treg cell percentage and evaluate PD-1 and PD-L1 expression across the T and B cells. We observed a significantly higher percentage of Tregs in idiopathic PAH (iPAH) patients compared to healthy controls and those with congenital heart disease-associated PAH (CHD-PAH), connective tissue disease-associated PAH (CTD-PAH), and chronic thromboembolic pulmonary hypertension (CTEPH). An overexpression of PD-1 and PD-L1 was found on CD4+ and CD8+ lymphocytes in all PAH groups, particularly in iPAH and CHD-PAH patients. These findings align with previous research highlighting Treg dysfunction and PD-1/PD-L1 overexpression as contributors to PAH pathogenesis. Our results suggest that targeting immune checkpoints and modulating Treg function could represent novel therapeutic strategies for PAH. Future research should focus on validating these biomarkers in larger, independent cohorts and exploring their clinical utility in diagnosing and managing PAH.