{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T16:11:37Z","timestamp":1791216697454,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2013,10,28]],"date-time":"2013-10-28T00:00:00Z","timestamp":1382918400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Respirology"],"published-print":{"date-parts":[[2013,11]]},"abstract":"Abstract<\/jats:title>Background and objective<\/jats:title>Increasing evidence implicates lymphocytes in pulmonary arterial hypertension (PAH<\/jats:styled-content>) pathogenesis. Rats deficient in T<\/jats:styled-content>\u2010lymphocytes show increased propensity to develop PAH<\/jats:styled-content> but when injected with endothelial progenitor cells are protected from PAH<\/jats:styled-content> (a mechanism dependent on natural killer (NK<\/jats:styled-content>) cells). A decreased quantity of circulating cytotoxic CD8<\/jats:styled-content>+ T<\/jats:styled-content>\u2010lymphocytes and NK<\/jats:styled-content> cells are now reported in PAH<\/jats:styled-content> patients; however, the effect of lymphocyte depletion on disease outcome is unknown.<\/jats:p><\/jats:sec>Methods<\/jats:title>This prospective study analysed the lymphocyte profile and plasma brain natriuretic peptide (BNP<\/jats:styled-content>) levels of patients with idiopathic PAH<\/jats:styled-content> (IPAH<\/jats:styled-content>), connective tissue disease\u2010associated PAH<\/jats:styled-content> (CTD<\/jats:styled-content>\u2010APAH<\/jats:styled-content>) and matched healthy controls. Lymphocyte surface markers studied include: CD4<\/jats:styled-content>+ (helper T<\/jats:styled-content>\u2010cell marker), CD8<\/jats:styled-content>+ (cytotoxic T<\/jats:styled-content>\u2010cell marker), CD56<\/jats:styled-content>\/CD16<\/jats:styled-content> (NK<\/jats:styled-content> cell marker) and CD19<\/jats:styled-content>+ (mature B<\/jats:styled-content>\u2010cell marker). Lymphocyte deficiencies and plasma BNP<\/jats:styled-content> levels were then correlated with clinical outcome.<\/jats:p><\/jats:sec>Results<\/jats:title>Fourteen patients with PAH<\/jats:styled-content> (9 IPAH<\/jats:styled-content>, 5CTD<\/jats:styled-content>) were recruited. Three patients were deceased at 1\u2010year follow\u2010up; all had elevated CD4<\/jats:styled-content>\u2009:\u2009CD8<\/jats:styled-content> ratios and deficiencies of NK<\/jats:styled-content> cells and cytotoxic CD8<\/jats:styled-content>+ T<\/jats:styled-content>\u2010lymphocytes 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<\/jats:styled-content>+ T<\/jats:styled-content>\u2010cell and NK<\/jats:styled-content> cell counts were linked to short\u2010term survival.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>Deficiencies in NK<\/jats:styled-content> cells and cytotoxic CD8<\/jats:styled-content>+ T<\/jats:styled-content>\u2010cells may be associated with an increased risk of death in PAH<\/jats:styled-content> patients. Further research is required in larger numbers of patients and to elucidate the mechanism of these findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/resp.12152","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T11:21:59Z","timestamp":1372764119000},"page":"1271-1277","source":"Crossref","is-referenced-by-count":31,"title":["Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension"],"prefix":"10.1111","volume":"18","author":[{"given":"Adrienne L","family":"Edwards","sequence":"first","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"},{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah P","family":"Gunningham","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey C","family":"Clare","sequence":"additional","affiliation":[{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew W","family":"Hayman","sequence":"additional","affiliation":[{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Smith","sequence":"additional","affiliation":[{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher MA","family":"Frampton","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget A","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"},{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W","family":"Troughton","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lutz EL","family":"Beckert","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Otago Christchurch New Zealand"},{"name":"Canterbury District Health Board Christchurch New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,10,28]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehp297"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.012"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.02.029"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201201-0164OC"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.04.006"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200608-1189OC"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2009-0152OC"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111548"},{"key":"e_1_2_7_10_1","first-page":"37","article-title":"Immune markers of pulmonary arterial hypertension","volume":"13","author":"Edwards AL","year":"2010","journal-title":"Crit. 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