Abstract 1630: Decreased 5′-nucleotidase (CD73) On T Lymphocytes Of Patients With Idiopathic Pulmonary Arterial Hypertension
Idiopathic pulmonary artery hypertension (IPAH) is a devastating disease characterized by precapillary vascular narrowing and increased pulmonary vascular resistance. The vascular pathobiology of IPAH includes lumen-obstructing plexiform lesions with perivascular inflammatory infiltrates containing T lymphocytes. Certain effector subsets of T lymphocytes may contribute to the pathologic vascular remodeling seen in IPAH. We considered whether enzymes known to be present on the surface of regulatory T cells might be altered in idiopathic pulmonary arterial hypertension (IPAH). These enzymes, CD39 and CD73, catalyze the phosphohydrolysis of extracellular purinergic nucleotides to generate adenosine. Surface expression of CD39 and CD73 was measured by flow cytometry of fresh blood obtained from IPAH through the Pulmonary Hypertension Breakthrough Initiative national network. CD3+ gating was employed to identify T cell populations expressing surface CD39 or CD73. Whole blood samples from 22 healthy controls and 23 patients with IPAH were studied. Samples from patients with IPAH showed a decrease in T cell CD73 expression as compared to controls [mean fluorescent intensity (MFI) 12.6 ± 2.0 vs 19.2 ± 2.2, p < 0.05]. There was no difference in the expression of CD39 (20.5 ± 3.9 MFI in controls vs. 17.5 ± 2.5 in IPAH patients, p = ns). Decreased CD73 expression on the circulating T lymphocytes of patients with IPAH is a novel finding, and supports the hypothesis that cell surface enzymes which metabolize pro-inflammatory and pro-coagulant extracellular nucleotides and generate vasodilatory and anti-inflammatory adenosine might have a fundamental role in the pathophysiology of IPAH.