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Respirology. 2013 Nov;18(8):1271-7. doi: 10.1111/resp.12152.

Professional killer cell deficiencies and decreased survival in pulmonary arterial hypertension.

Author information

1
Department of Medicine, University of Otago, Christchurch, New Zealand; Canterbury District Health Board, Christchurch, New Zealand.

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, 5CTD) 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.

KEYWORDS:

biomarker; cytotoxic CD8+ T-lymphocyte; immunology; natural killer cell; pulmonary arterial hypertension

PMID:
23819819
DOI:
10.1111/resp.12152
[Indexed for MEDLINE]
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