Quantitative and Functional Analysis of PD-1 NK Cells in Patients with Autoimmune Thyroid Disease
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Context: Natural killer (NK) cells have an important role in innate immunity and in the regulation of immune response.The role of NK cells expressing the programmed cell death protein-1 (PD-1) regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD). Purpose: To analyze the levels and function of PD-1 NK cells in samples from AITD patients. Design: Cases and controls, observational study. Setting: Hospital Universitario la Princesa, Spain. Patients: Forty patients with AITD, 16 with Hashimoto thyroiditis (HT), 24 with Graves’ disease (GD), and 15 healthy controls. Intervention: Multiparametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines. Main outcome measures: Levels and function of PD-1 NK cells in blood samples from AITD patients and controls. Results: Increased levels of NK cells and the CD56dimPD-1 subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56brightPD-1 NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56brightPD-1– NK cells, whereas CD56dimPD-1 cells from GD patients exhibited an enhanced production of interferon-γ. PD-1 NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1 NK cells and clinical laboratory parameters. Conclusions: The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients’ further support the complex role of these cells in this pathogenesis. © Endocrine Society 2020. All rights reserved.
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Context: Natural killer (NK) cells have an important role in innate immunity and in the regulation of immune response.The role of NK cells expressing the programmed cell death protein-1 (PD-1) regulatory receptor has not been explored in patients with autoimmune thyroid disease (AITD). Purpose: To analyze the levels and function of PD-1%2b NK cells in samples from AITD patients. Design: Cases and controls, observational study. Setting: Hospital Universitario la Princesa, Spain. Patients: Forty patients with AITD, 16 with Hashimoto thyroiditis (HT), 24 with Graves’ disease (GD), and 15 healthy controls. Intervention: Multiparametric flow cytometry analysis of peripheral blood NK cells. In vitro assays of cytotoxic activity of NK cells, and synthesis of cytokines. Main outcome measures: Levels and function of PD-1%2b NK cells in blood samples from AITD patients and controls. Results: Increased levels of NK cells and the CD56dimPD-1%2b subset were observed in GD patients. In HT, an enhanced expression of the regulatory receptors NKG2A and NKG2C by CD56brightPD-1%2b NK cells was detected. AITD patients showed an increased synthesis of IL-10 by CD56brightPD-1– NK cells, whereas CD56dimPD-1%2b cells from GD patients exhibited an enhanced production of interferon-γ. PD-1%2b NK cells from patients with GD and HT showed an increased cytotoxic activity. Significant associations were observed in patients with GD or HT between the levels of PD-1%2b NK cells and clinical laboratory parameters. Conclusions: The different abnormalities in NK cell subset levels, in the expression of PD-1 and its function in AITD patients’ further support the complex role of these cells in this pathogenesis. © Endocrine Society 2020. All rights reserved.
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Autoimmune thyroid disease; NK cells; Programmed cell death protein-1 CD56 antigen; cytokine; gamma interferon; interleukin 10; programmed death 1 receptor; adult; Article; autoimmune thyroiditis; blood; clinical article; clinical laboratory; controlled study; cytokine production; cytotoxicity; degranulation; female; flow cytometry; Graves disease; Hashimoto disease; human; immune response; in vitro study; innate immunity; male; multiparametric magnetic resonance imaging; natural killer cell; observational study; pathogenesis; priority journal; quantitative analysis; Spain
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