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Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality

OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells...

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Autores principales: Bancos, Irina, Hazeldine, Jon, Chortis, Vasileios, Hampson, Peter, Taylor, Angela E, Lord, Janet M, Arlt, Wiebke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425935/
https://www.ncbi.nlm.nih.gov/pubmed/28223394
http://dx.doi.org/10.1530/EJE-16-0969
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author Bancos, Irina
Hazeldine, Jon
Chortis, Vasileios
Hampson, Peter
Taylor, Angela E
Lord, Janet M
Arlt, Wiebke
author_facet Bancos, Irina
Hazeldine, Jon
Chortis, Vasileios
Hampson, Peter
Taylor, Angela E
Lord, Janet M
Arlt, Wiebke
author_sort Bancos, Irina
collection PubMed
description OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection. DESIGN AND METHODS: We undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis (n = 37) or bilateral adrenalectomy (n = 5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects. RESULTS: Neutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P < 0.0001). Phenotypically, the percentage of NK cells expressing the activating receptors NKG2D and NKp46 was significantly lower in PAI, as was the surface density of NKG2D (all P < 0.0001). Intracellular granzyme B expression was significantly increased in NK cells from PAI patients (P < 0.01). CONCLUSIONS: Adrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI.
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spelling pubmed-54259352017-05-15 Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality Bancos, Irina Hazeldine, Jon Chortis, Vasileios Hampson, Peter Taylor, Angela E Lord, Janet M Arlt, Wiebke Eur J Endocrinol Clinical Study OBJECTIVE: Mortality in patients with primary adrenal insufficiency (PAI) is significantly increased, with respiratory infections as a major cause of death. Moreover, patients with PAI report an increased rate of non-fatal infections. Neutrophils and natural killer (NK) cells are innate immune cells that provide frontline protection against invading pathogens. Thus, we compared the function and phenotype of NK cells and neutrophils isolated from PAI patients and healthy controls to ascertain whether altered innate immune responses could be a contributory factor for the increased susceptibility of PAI patients to infection. DESIGN AND METHODS: We undertook a cross-sectional study of 42 patients with PAI due to autoimmune adrenalitis (n = 37) or bilateral adrenalectomy (n = 5) and 58 sex- and age-matched controls. A comprehensive screen of innate immune function, consisting of measurements of neutrophil phagocytosis, reactive oxygen species production, NK cell cytotoxicity (NKCC) and NK cell surface receptor expression, was performed on all subjects. RESULTS: Neutrophil function did not differ between PAI and controls. However, NKCC was significantly reduced in PAI (12.0 ± 1.5% vs 21.1 ± 2.6%, P < 0.0001). Phenotypically, the percentage of NK cells expressing the activating receptors NKG2D and NKp46 was significantly lower in PAI, as was the surface density of NKG2D (all P < 0.0001). Intracellular granzyme B expression was significantly increased in NK cells from PAI patients (P < 0.01). CONCLUSIONS: Adrenal insufficiency is associated with significantly decreased NKCC, thereby potentially compromising early recognition and elimination of virally infected cells. This potential impairment in anti-viral immune defense may contribute to the increased rate of respiratory infections and ultimately mortality in PAI. Bioscientifica Ltd 2017-01-23 /pmc/articles/PMC5425935/ /pubmed/28223394 http://dx.doi.org/10.1530/EJE-16-0969 Text en © 2017 The authors http://creativecommons.org/licenses/by/3.0/ This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/) .
spellingShingle Clinical Study
Bancos, Irina
Hazeldine, Jon
Chortis, Vasileios
Hampson, Peter
Taylor, Angela E
Lord, Janet M
Arlt, Wiebke
Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title_full Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title_fullStr Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title_full_unstemmed Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title_short Primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
title_sort primary adrenal insufficiency is associated with impaired natural killer cell function: a potential link to increased mortality
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5425935/
https://www.ncbi.nlm.nih.gov/pubmed/28223394
http://dx.doi.org/10.1530/EJE-16-0969
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