Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension

Abstract Background and objective Increasing evidence implicates lymphocytes in pulmonary arterial hypertension ( PAH ) pathogenesis. Rats deficient in T ‐lymphocytes show increased propensity to develop PAH but when injected with endothelial progenitor cells are protected from PAH (a mechanism dependent on natural killer ( NK ) cells). A decreased quantity of circulating cytotoxic CD8 + T ‐lymphocytes and NK cells are now reported in PAH patients; however, the effect of lymphocyte depletion on disease outcome is unknown. Methods This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide ( BNP ) levels of patients with idiopathic PAH ( IPAH ), connective tissue disease‐associated PAH ( CTD ‐ APAH ) and matched healthy controls. Lymphocyte surface markers studied include: CD4 + (helper T ‐cell marker), CD8 + (cytotoxic T ‐cell marker), CD56 / CD16 ( NK cell marker) and CD19 + (mature B ‐cell marker). Lymphocyte deficiencies and plasma BNP levels were then correlated with clinical outcome. Results Fourteen patients with PAH (9 IPAH , 5 CTD ) were recruited. Three patients were deceased at 1‐year follow‐up; all had elevated CD4 : CD8 ratios and deficiencies of NK cells and cytotoxic CD8 + T ‐lymphocytes at recruitment. Patients with normal lymphocyte profiles at recruitment were all alive a year later, and none were on the active transplant list. As univariate markers, cytotoxic CD8 + T ‐cell and NK cell counts were linked to short‐term survival. Conclusions Deficiencies in NK cells and cytotoxic CD8 + T ‐cells may be associated with an increased risk of death in PAH patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings.