Natural killer cell lymphocytosis as a cause of pulmonary arterial hypertension: A case report.

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Pulmonary arterial hypertension (PAH) is associated with a number of myeloproliferative disorders. We describe a case of PAH in the setting of natural killer (NK) cell lymphocytosis when all other etiologies have been ruled out. CASE PRESENTATION: A middle aged female with a history of chronic obstructive pulmonary disease on home oxygen and NK lymphocytosis was hospitalized for acute on chronic hypoxemic respiratory failure and New York Heart Association (NYHA) Functional Class (FC) IV symptoms. Laboratory evaluation showed a brain natriuretic peptide of 2380 pg/mL. 2-dimensional echocardiography demonstrated a RVSP of 75 with severely dilated right ventricle (RV), flattening of the interventricular septum in systole and diastole, RV fractional area change of 19.4% and tricuspid annual place systolic excursion of 0.97 cm. Spirometry showed an obstructive pattern. Ventilation perfusion scan was low probability for pulmonary embolism. Right heart catheterization demonstrated, in mmHg, right atrial pressure 13, mean pulmonary artery pressure of 56, pulmonary capillary wedge pressure of 6, cardiac output of 2.39 L/min and cardiac index of 1.27 L/min /m2 by Fick method with a pulmonary vascular resistance of 20.9 Woods units. Computed tomography of the chest demonstrated only mild emphysema. Flow cytometry showed significant NK cell lymphocytosis with no evidence of B-cell or T-cell lymphoma. Group 1 PAH was diagnosed as there was discordance between PAH severity and parenchymal changes on imaging. Diuretics and intravenous treprostinil were initiated. Macitentan was later added with significant improvement in BNP, RV morphology and function, NYHA FC and six minute walk distance. DISCUSSION: To our knowledge, this is the first reported case of PAH developing in the setting of NK cell lymphocytosis in humans. NK cell lymphocytosis is characterized by peripheral blood and bone marrow infiltration with abnormal clonal lymphocytes. Recently, proliferation of abnormal NK cells has been shown in patients with PAH and in animal models. In patients with PAH a proliferation of functionally deficient subset of NK cells CD56-/CD16+ was observed which was not present in a disease control group of patients with group 4 disease suggesting that observed NK cell dysfunction is specific to PAH. It is proposed that NK cells play a significant role in regulation of vascular remodeling and regeneration and their alteration may play a role in the pathophysiology of the disease. CONCLUSIONS: There is an established association between abnormal NK cell proliferation and PAH. We describe a patient with PAH in the setting of NK lymphocytosis who improved significantly with initiation of parenteral prostacyclin therapy. More research is needed to determine the role of NK cells in the development of PAH in humans.





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