Gadintshware Gaoatswe1, Brian D Kent2, Michelle A Corrigan1, Geraldine Nolan2, Andrew E Hogan1,3, Walter T McNicholas2, Donal O'Shea1. 1. Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland. 2. Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland. 3. Obesity Immunology Group, National Children's Research Center, Dublin, Ireland.
Abstract
STUDY OBJECTIVES: Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA. DESIGN: We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production. SETTING: Teaching hospital based sleep unit and research laboratory. PATIENTS: Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). MEASUREMENTS AND RESULTS: Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035). CONCLUSION: Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA.
STUDY OBJECTIVES: Emerging evidence links obstructive sleep apnea (OSA) with increased cancer incidence and mortality. Invariant natural killer T (iNKT) cells play an important role in cancer immunity. We hypothesized that patients with OSA have low number of circulating invariant natural killer T (iNKT) cells, which may also be functionally impaired. This study aims to evaluate the frequency of circulating iNKT cells in OSA. DESIGN: We evaluated the frequency of circulating iNKT cells by flow cytometry in 33 snorers being assessed for possible OSA. Using iNKT cell lines, we also evaluated the effect of exposure to hypoxia over 24 hours on apoptosis, cytotoxicity, and cytokine production. SETTING: Teaching hospital based sleep unit and research laboratory. PATIENTS: Thirty-three snorers were evaluated: 9 with no OSA (apnea-hypopnea frequency [AHI] < 5/h), 12 with mild-moderate OSA (AHI 5-30) and 12 with severe OSA (AHI > 30). MEASUREMENTS AND RESULTS:Patients with severe OSA had considerably fewer iNKT cells (0.18%) compared to patients with mild-moderate (0.24%) or no OSA (0.35%), P = 0.0026. The frequency of iNKT cells correlated negatively with apnea-hypopnea index (r = -0.58, P = 0.001), oxygen desaturation index (r = -0.58, P = 0.0003), and SpO2% < 90% (r = -0.5407, P = 0.005). The frequency of iNKT cells increased following 12 months of nCPAP therapy (P = 0.015). Hypoxia resulted in increased apoptosis (P = 0.016) and impaired cytotoxicity (P = 0.035). CONCLUSION:Patients with obstructive sleep apnea (OSA) have significantly reduced levels of circulating invariant natural killer T (iNKT) cells and hypoxia leads to impaired iNKT cell function. These observations may partly explain the increased cancer risk reported in patients with OSA.
Authors: Giuseppe Giaccone; Cornelis J A Punt; Yoshitaka Ando; Rita Ruijter; Nobusuke Nishi; Marlies Peters; B Mary E von Blomberg; Rik J Scheper; Hans J J van der Vliet; Alfons J M van den Eertwegh; Marja Roelvink; Jos Beijnen; Heinz Zwierzina; Herbert M Pinedo Journal: Clin Cancer Res Date: 2002-12 Impact factor: 12.531
Authors: T Kawano; J Cui; Y Koezuka; I Toura; Y Kaneko; H Sato; E Kondo; M Harada; H Koseki; T Nakayama; Y Tanaka; M Taniguchi Journal: Proc Natl Acad Sci U S A Date: 1998-05-12 Impact factor: 11.205
Authors: T Kawano; T Nakayama; N Kamada; Y Kaneko; M Harada; N Ogura; Y Akutsu; S Motohashi; T Iizasa; H Endo; T Fujisawa; H Shinkai; M Taniguchi Journal: Cancer Res Date: 1999-10-15 Impact factor: 12.701
Authors: Johan W Molling; Wendy Kölgen; Hans J J van der Vliet; Martijn F Boomsma; Hinke Kruizenga; Carolien H Smorenburg; Barbara G Molenkamp; Johannes A Langendijk; C René Leemans; B Mary E von Blomberg; Rik J Scheper; Alfons J M van den Eertwegh Journal: Int J Cancer Date: 2005-08-10 Impact factor: 7.396
Authors: Francisco Campos-Rodriguez; Miguel A Martinez-Garcia; Montserrat Martinez; Joaquin Duran-Cantolla; Monica de la Peña; María J Masdeu; Monica Gonzalez; Felix del Campo; Inmaculada Gallego; Jose M Marin; Ferran Barbe; Jose M Montserrat; Ramon Farre Journal: Am J Respir Crit Care Med Date: 2012-11-15 Impact factor: 21.405
Authors: David H Chang; Keren Osman; John Connolly; Anjli Kukreja; Joseph Krasovsky; Maggi Pack; Aisha Hutchinson; Matthew Geller; Nancy Liu; Rebecca Annable; Jennifer Shay; Kelly Kirchhoff; Nobusuke Nishi; Yoshitaka Ando; Kunihiko Hayashi; Hani Hassoun; Ralph M Steinman; Madhav V Dhodapkar Journal: J Exp Med Date: 2005-05-02 Impact factor: 14.307
Authors: Marco Dal Molin; Aaron Brant; Amanda L Blackford; James F Griffin; Koji Shindo; Thomas Barkley; Neda Rezaee; Ralph H Hruban; Christopher L Wolfgang; Michael Goggins Journal: PLoS One Date: 2016-10-12 Impact factor: 3.240
Authors: Richard Staats; Raquel Rodrigues; André Barros; Leonor Bacelar-Nicolau; Margarida Aguiar; Dina Fernandes; Susana Moreira; André Simões; Bruno Silva-Santos; João Valença Rodrigues; Cristina Barbara; António Bugalho de Almeida; Luis Ferreira Moita Journal: Sleep Breath Date: 2017-12-15 Impact factor: 2.816