Natural killer cell-mediated immune deficiency or compromise in patients with portopulmonary hypertension

Portopulmonary hypertension (POPH) is a form of pulmonary arterial hypertension (PAH) in the setting of portal hypertension, and is associated with a poor prognosis [1]. The underling etiological cause of POPH is poorly understood [1]. Previously we have reported T cell-mediated immune deficiency or compromise in patients with chronic thromboembol-ic pulmonary hypertension (CTEPH), idiopathic pulmonary hypertension (IPH), and acute pulmonary embolism (APE) [2, 3]. Here we report natural killer cell-mediated immune deficiency or compromise in patients with POPH. Nine patients (4 male, 5 female) diagnosed with POPH in Shanghai Tongji Hospital from year 2010 to 2011 were recruited in the present study, with a mean age of 65 ±19 years (30–82 years). The diagnosis of POPH is based on the hemodynamic criteria including portal hypertension and/ or liver disease (clinical diagnosis) [4], pulmonary artery systolic pressure > 40 mm Hg at rest, pulmonary vascular resistance > 240 dynes × s × cm –5 , and pulmonary artery occlusion pressure < 15 mm Hg or transpulmonary gradient > 12 [1]. We firstly detected the cluster of differentiation (CD) on the T cell surface. To our surprise, unlike the changes we previously reported in CTEPH, IPH, or APE, only slight changes of CD3+, CD4+ or CD8+ T cells were observed in POPH patients (Table I and Figures 1 A–C). Interestingly, the number of CD16+CD56, which reflects the function of natural killer cell, was decreased in five patients with POPH (55.6%) (Table I and Figure 1 D) [5]. T cell-mediated immune deficiency or compromise has been reported in patients with CTEPH, IPH, and APE [2, 3]. In the present study, we failed to detect obvious cell-mediated immune changes. Natural killer cells, accounting for 15% of peripheral blood lymphocytes, are well-known unique effectors of the innate immune system as they can recognize stressed cells in the absence of antibodies and MHC [3]. As the role of natural killer cells is analogous to that of cytotoxic T cells [5], we detected their surface markers CD16 (FcγRIII) and CD56 in POPH patients and identified a natural killer cell-mediated immune deficiency or compromise in patients with POPH. Immune deficiency or compromise of natural killer cells is usually caused by virus infection, cancer, or im-munosuppressive drugs [5]. In this study, malignant tumors or use of immunosuppressive drugs were excluded in these 9 patients; therefore the immune deficiency or compromise of natural killer cells is most likely due to …