Differential expression of immune markers in the patients with obstructive sleep apnea/hypopnea syndrome

  • Hong Xie
  • Jinshu YinEmail author
  • Yunbo Bai
  • Hong Peng
  • Xiaohong Zhou
  • Juan Bai



To evaluate phenotypic changes of various immune cells in the peripheral blood in the patients with sleep apnea/hypopnea syndrome (OSAHS).


This is a case–control study. The peripheral venous blood was collected. A subset of T cells, B cells, natural killer cells, and dendritic cells was analysed using various markers and flow cytometry. Regression curve analysis was made to examine the correlation between the change of immune cells and aponea hypoxia index (AHI) and oxygen desaturation.


The percentage of CD3+/CD4+ T lymphocytes (P < 0.001) and CD19+ B cells (P < 0.001) and the CD4+/CD8+ ratio (P < 0.001) in the OSAHS patients were significantly increased compared with those in the control group without OSAHS, and CD4+/CD8+ ratio positively correlated with aponea hypoxia index (r = 0.37, P < 0.001) but negatively correlated with the lowest SaO2 (r = − 0.2, P < 0.001), whereas a greater reduction in the percentage of CD3+/CD8+ T cells (P < 0.001). Moreover, the ratios of CD3+/CD16+/CD56+ natural killer (NK)-like T cells (P < 0.05) and CD3/CD16+/CD56+ NKT cells (P < 0.001) were significantly lower in the OSAHS group than those in the control group. However, no significant difference was observed in the percentage of CD3+ total T cells, CD8+/CD28+ T cells, CD8+/CD28 T cells, DC1, DC2, and DC1/DC2 dendritic cells between the OSAHS and control groups.


Our study showed differential responses of various types of immune cells in the peripheral blood in patients with OSAHS and their correlation with severity of oxygen desaturation.


T cells B cells Natural killer cells Dendritic cells Flow cytometry Obstructive sleep aponea 


Compliance with ethical standards

Conflict of interest

Hong Xie has no conflict of interest, Jinshu Yin has no conflict of interest, Yunbo Bai has no conflict of interest, Hong Peng has no conflict of interest, Xiaohong Zhou has no conflict of interest, and Juan Bai has no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

All participants were informed about the study and signed an informed consent form. This study was approved by the Ethical Committee of Beijing Shijitan Hospital.


  1. 1.
    Mbata G, Chukwuka J (2012) Obstructive sleep apnea hypopnea syndrome. Ann Med Health Sci Res 2(1):74CrossRefGoogle Scholar
  2. 2.
    Gale SD, Hopkins RO (2004) Effects of hypoxia on the brain: neuroimaging and neuropsychological findings following carbon monoxide poisoning and obstructive sleep apnea. J Int Neuropsychol Soc 10(1):60–71CrossRefGoogle Scholar
  3. 3.
    Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM (2013) Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol 177(9):1006–1014. CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Mingari MC, Ponte M, Bertone S, Schiavetti F, Vitale C, Bellomo R, Moretta A, Moretta L (1998) HLA class I-specfiic inhibitory receptors in human T lymphocytes: interleukin 15-induced expression of CD94/NKG2A in superantigen-or alloantigen-activated CD8 + T cells. Proc Natl Acad Sci U S A 95(3):1172–1177CrossRefGoogle Scholar
  5. 5.
    Dyugovskaya L, Lavie P, Lavie L (2005) Lymphocyte activation as a possible measure of atherosclerotic risk in patients with sleep apnea. Ann N Y Acad Sci 1051:340–350CrossRefGoogle Scholar
  6. 6.
    Valham F, Mooe T, Rabben T, Stenlund H, Wiklund U, Franklin KA (2008) Increased risk of stroke in patients with coronary artery disease and sleep apnea: a 10-year follow-up. Circulation 118(9):955–960. CrossRefPubMedGoogle Scholar
  7. 7.
    Dempsey JA, Veasey SC, Morgan BJ, O’Donnell CP (2010) Pathophysiology of sleep apnea. Physiol Rev 90(1):47–112. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Peker Y, Carlson J, Hedner J (2006) Increased incidence of coronary artery. Eur Respir J 28(3):596–602CrossRefGoogle Scholar
  9. 9.
    Drager LF, McEvoy RD, Barbe F, Lorenzi-Filho G, Redline S, INCOSACT Initiative (International Collaboration of Sleep Apnea Cardiovascular Trialists) (2017) Sleep apnea and cardiovascular disease: lessons from recent trials and need for team science. Circulation 136(19):1840–1850CrossRefGoogle Scholar
  10. 10.
    Strohl KP, Redline S (1996) Recognition of obstructive sleep apnea. Am J Respir Crit Care Med 154(2 Pt 1):279–289CrossRefGoogle Scholar
  11. 11.
    Yaggi HK, Concato J, Kernan WN, Lichtman JH, Brass LM, Mohsenin V (2005) Obstructive sleep apnea as a risk factor for stroke and death. N Engl J Med 353(19):2034–2041CrossRefGoogle Scholar
  12. 12.
    Wieckowski EU, Visus C, Szajnik M, Szczepanski MJ, Storkus WJ, Whiteside TL (2009) Tumor-derived microvesicles promote regulatory T cell expansion and induce apoptosis in tumor-reactive activated CD8 + T lymphocytes. J Immunol 183(6):3720–3730CrossRefGoogle Scholar
  13. 13.
    Azagra-Calero E, Espinar-Escalona E, Barrera-Mora JM, Llamas-Carreras JM, Solano-Reina E (2012) Obstructive sleep apnea syndrome (OSAS): review of the literature. Med Oral Patol Oral Cir Bucal 17(6):e925–e929CrossRefGoogle Scholar
  14. 14.
    Zhang Z, Wang C (2017) Immune status of children with obstructive sleep apnea/hypopnea syndrome. Pak J Med Sci 33(1):195–199PubMedPubMedCentralGoogle Scholar
  15. 15.
    Coman AC, Borzan C, Vesa CS, Todea DA (2016) Obstructive sleep apnea syndrome and the quality of life. Clujul Med 89(3):390–395. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Fleming WE, Ferouz-Colborn A, Samoszuk MK, Azad A, Lu J, Riley JS, Cruz AB, Podolak S, Clark DJ, Bray KR, Southwick PC (2016) Blood biomarkers of endocrine, immune, inflammatory, and metabolic systems in obstructive sleep apnea. Clin Biochem 49(12):854–861. CrossRefPubMedGoogle Scholar
  17. 17.
    Geiger SS, Fagundes CT, Siegel RM (2015) Chrono-immunology: progress and challenges in understanding links between the circadian and immune systems. Immunology 146(3):349–358. CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Murphy K (2017) Janeway’s immunobiology (9 th. edn.). Garland Science Taylor & Francis Group, LLC, New YorkGoogle Scholar
  19. 19.
    Gozal D, Farré R, Nieto FJ (2015) Putative links between sleep apnea and cancer: from hypotheses to evolving evidence. Chest 148(5):1140–1147. CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Dyugovskaya L, Lavie P, Lavie L (2003) Phenotypic and functional characterization of blood gammadelta T cells in sleep apnea. Am J Respir Crit Care Med 168(2):242–249CrossRefGoogle Scholar
  21. 21.
    Dyugovskaya L, Lavie P, Hirsh M, Lavie L (2005) Activated CD8 + T-lymphocytes in obstructive sleep apnoea. Eur Respir J 25(5):820–828CrossRefGoogle Scholar
  22. 22.
    Kim J, Bhattacharjee R, Dayyat E, Snow AB, Kheirandish-Gozal L, Goldman JL, Li RC, Serpero LD, Clair HB, Gozal D (2009) Increased Cellular Proliferation And Inflammatory Cytokines In Tonsils Derived From Children With Obstructive Sleep Apnea. Pediatr Res 66(4):423–428. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Qin YH, Cai Z, Qiu YR (2010) T cell subsets and NK cell level in patients with obstructive sleep apnea/hypopnea syndrome. Guangdong Med J 31(5):615–616Google Scholar
  24. 24.
    Zhang Z, Wang C (2017) Immune status of children with obstructive sleep apnea/hypopnea syndrome. Pak J Med Sci 33(1):195–199. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Staats R, Rodrigues R, Barros A, Bacelar-Nicolau L, Aguiar M, Fernandes D, Moreira S, Simões A, Silva-Santos B, Rodrigues JV, Barbara C, de Almeida AB, Moita LF (2018) Decrease of perforin positive CD3+γδ-T cells in patients with obstructive sleep disordered breathing. Sleep Breath 22(1):211–221. CrossRefPubMedGoogle Scholar
  26. 26.
    Domagała-Kulawik J, Osińska I, Piechuta A, Bielicki P, Skirecki T (2015) T, B, and NKT Cells in systemic inflammation in obstructive sleep apnoea. Mediators Inflamm 2015:161579. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gaoatswe G, Kent BD, Corrigan MA, Nolan G, Hogan AE, McNicholas WT, O’Shea D (2015) Invariant natural killer T cell deficiency and functional impairment in sleep apnea: links to cancer comorbidity. Sleep 38(10):1629–1634. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Editing committee of Chinese Journal of Otorhinolaryngology Head and Neck Surgery (2002) Diagnostic criteria for OSAHS and criteria for outcome evaluation and indication of Uvulopalatopharyngoplasty. Chin J Otorhinolaryngol Head Neck Surg 37:403–404Google Scholar
  29. 29.
    Ye JY, Li WY (2009) Diagnosis and guideline for surgical treatment of OSAHS. Chin J Otorhinolaryngol Head Neck Surg 44:91–94Google Scholar
  30. 30.
    Ryan S, Taylor CT, McNicholas WT (2006) Predictors of elevated nuclear factor-kappaB-dependent genes in obstructive sleep apnea syndrome. Am J Respir Crit Care Med 174(7):824–830CrossRefGoogle Scholar
  31. 31.
    Unnikrishnan D, Jun J, Polotsky V (2015) Inflammation in sleep apnea: an update. Rev Endocr Metab Disord 16(1):25–34. CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Vicente E, Marin JM, Carrizo SJ, Osuna CS, González R, Marin-Oto M, Forner M, Vicente P, Cubero P, Gil AV, Soler X (2016) Upper airway and systemic inflammation in obstructive sleep apnoea. Eur Respir J 48(4):1108–1117. CrossRefPubMedGoogle Scholar
  33. 33.
    Bollinger T, Bollinger A, Skrum L, Dimitrov S, Lange T, Solbach W (2009) Sleep-dependent activity of T cells andregulatory T cells. Clin Exp Immunol 155(2):231–238. CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Freire AX, Kadaria D, Avecillas JF, Murillo LC, Yataco JC (2010) Obstructive sleep apnea and immunity: relationship of lymphocyte count and apnea hypopnea index. South Med J 103(8):771–774. CrossRefPubMedGoogle Scholar
  35. 35.
    McNamee EN, Korns Johnson D, Homann D, Clambey ET (2013) Hypoxia and hypoxia-inducible factors as regulators of T cell development, differentiation, and function. Immunol Res 55(1–3):58–70. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Vroom TM1, Scholte G, Ossendorp F, Borst J (1991) Tissue distribution of human gamma delta T cells: no evidence for general epithelial tropism. J Clin Pathol 44(12):1012–1017CrossRefGoogle Scholar
  37. 37.
    Punit S, Dubé PE, Liu CY, Girish N, Washington MK, Polk DB (2015) Tumor necrosis factor receptor 2 restricts the pathogenicity of CD8(+) T cells in mice with colitis. Gastroenterology 149(4):993–1005.e2. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Akbarpour M, Khalyfa A, Qiao Z, Gileles-Hillel A, Almendros I, Farré R, Gozal D (2017) Altered CD8+ T-Cell lymphocyte function and TC1 Cell stemness contribute to enhanced malignant tumor properties in murine models of sleep apnea. Sleep 40(2).
  39. 39.
    Borthwick NJ, Lowdell M, Salmon M, Akbar AN (2000) Loss of CD28 expression on CD8+ T cells is induced by IL-2 receptor γ chain signalling cytokines and type I IFN, and increases susceptibility to activation-induced apoptosis. Int Immunol 12(7):1005–1013CrossRefGoogle Scholar
  40. 40.
    Prather AA, Gurfein B, Moran P, Daubenmier J, Acree M, Bacchetti P, Sinclair E, Lin J, Blackburn E, Hecht FM, Epel ES (2015) Tired telomeres: Poor global sleep quality, perceived stress, and telomere length in immune cell subsets in obese men and women. Brain Behav Immun 47:155–162. CrossRefPubMedGoogle Scholar
  41. 41.
    Effros RB, Dagarag M, Spaulding C, Man J (2005) The role of CD8+ T-cell replicative senescence in human aging. Immunol Rev 205:147–157CrossRefGoogle Scholar
  42. 42.
    Said EA, Al-Abri MA, Al-Saidi I, Al-Balushi MS, Al-Busaidi JZ, Al-Reesi I, Koh CY, Hasson SS, Idris MA, Al-Jabri AA, Habbal O (2017) Altered blood cytokines, CD4 T cells, NK and neutrophils in patients with obstructive sleep apnea. Immunol Lett 190:272–278. CrossRefPubMedGoogle Scholar
  43. 43.
    Sakaguchi S, Yamaguchi T, Nomura T, Ono M (2008) Regulatory T cells and immune tolerance. Cell 133(5):775–787. CrossRefPubMedGoogle Scholar
  44. 44.
    Ye J, Liu H, Zhang G, Li P, Wang Z, Huang S, Yang Q, Li Y (2012) The Treg/Th17 imbalance in patients with obstructive sleep apnoea syndrome. Mediators Inflamm 2012:815308. CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Takahashi T, Kuniyasu Y, Toda M, Sakaguchi N, Itoh M, Iwata M, Shimizu J, Sakaguchi S (1998) Immunologic self-tolerance maintained by CD25 + CD4 + naturally anergic and suppressive T cells: induction of autoimmune disease by breaking their anergic/suppressive state. Int Immunol 10(12):1969–1980CrossRefGoogle Scholar
  46. 46.
    Thounaojam MC, Dudimah DF, Pellom ST Jr, Uzhachenko RV, Carbone DP, Dikov MM, Shanker A (2016) Bortezomib enhances expression of effector molecules in antitumor CD8+ T lymphocytes by modulating Notch-NF-kB-miR-155 crosstalk. Oncotarget 6(32):32439–32455. CrossRefGoogle Scholar
  47. 47.
    Loza MJ, Perussia B (2004) Differential regulation of NK cell proliferation by type I and type II IFN. Int Immunol 16(1):23–32CrossRefGoogle Scholar
  48. 48.
    Freud AG, Mundy-Bosse BL, Yu J, Caligiuri MA (2017) The broad spectrum of human natural killer cell diversity. Immunity 2017;47(5):820–833. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Bisogni V, Pengo MF, Maiolino G, Rossi GP (2016) The sympathetic nervous system and catecholamines metabolism in obstructive sleep apnoea. J Thorac Dis 8(2):243–254. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Ben-Eliyahu S, Shakhar G, Page GG, Stefanski V, Shakhar K (2000) Suppression of NK cell activity and of resistance to metastasis by stress: a role for adrenal catecholamines and β-adrenoceptors. Neuroimmunomodulation 8(3):154–164CrossRefGoogle Scholar
  51. 51.
    Backteman K, Ernerudh J, Jonasson L (2014) Natural killer (NK) cell deficit in coronary artery disease: no aber’[rations in phenotype but sustained reduction of NK cells is associated with low-grade inflammation. Clin Exp Immunol 175(1):104–112. CrossRefPubMedGoogle Scholar
  52. 52.
    LeBien TW, Tedder TF (2008) B lymphocytes: how they develop and function. Blood 112(5):1570–1580CrossRefGoogle Scholar
  53. 53.
    BBurrows N, Maxwell PH (2017) Hypoxia and B cells. Exp Cell Res 356(2):197–203CrossRefGoogle Scholar
  54. 54.
    Collin M, Bigley V (2018) Human dendritic cell subsets: an update. Immunology 154(1):3–20. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bachem A, Güttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW, Henn V, Kloetzel PM, Gurka S, Kroczek RA (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c + CD141 + cells as homologues of mouse CD8+ dendritic cells. J Exp Med 207(6):1273–1281. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Winning S, Fandrey J (2016) Dendritic cells under hypoxia: how oxygen shortage affects the linkage between innate and adaptive immunity. J Immunol Res 2016:5134329. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Ahrens S, Zelenay S, Sancho D, Hanč P, Kjær S, Feest C, Fletcher G, Durkin C, Postigo A, Skehel M, Batista F, Thompson B, Way M, Reis e Sousa C, Schulz O (2012) F-actin is an evolutionarily conserved damage-associated molecular pattern recognized by DNGR-1, a receptor for dead cells. Immunity 36(4):635–645. CrossRefPubMedGoogle Scholar
  58. 58.
    Zhang JG, Czabotar PE, Policheni AN, Caminschi I, Wan SS, Kitsoulis S, Tullett KM, Robin AY, Brammananth R, van Delft MF, Lu J, O’Reilly LA, Josefsson EC, Kile BT, Chin WJ, Mintern JD, Olshina MA, Wong W, Baum J, Wright MD, Huang DC, Mohandas N, Coppel RL, Colman PM, Nicola NA, Shortman K, Lahoud MH (2012) The dendritic cell receptor Clec9A binds damaged cells via exposed actin filaments. Immunity 36:646–657CrossRefGoogle Scholar
  59. 59.
    Schraml BU, Reise Sousa C (2015) Defining dendritic cells. Curr Opin Immunol 32:13–20. CrossRefPubMedGoogle Scholar
  60. 60.
    Young T, Peppard PE, Taheri S (1985) Excess weight and sleep-disordered breathing. 99, 1592–1599Google Scholar
  61. 61.
    Shelton KE, Woodson H, Gay S, Suratt PM (1993) Pharyngeal fat in obstructive sleep apnea. Am Rev Respir Dis 148:462–466CrossRefGoogle Scholar
  62. 62.
    Morselli LL, Temple KA, Leproult R, Ehrmann DA, Van Cauter E, Mokhlesi B (2018) Determinants of slow-wave activity in overweight and obese adults: roles of sex, obstructive sleep apnea and testosterone levels. Front Endocrinol (Lausanne) 9:377. eCollection 2018CrossRefGoogle Scholar
  63. 63.
    Hudgel DW, Patel SR, Ahasic AM, Bartlett SJ, Bessesen DH, Coaker MA, Fiander PM, Grunstein RR, Gurubhagavatula I, Kapur VK, Lettieri CJ, Naughton MT, Owens RL, Pepin JD, Tuomilehto H, Wilson KC (2018) American Thoracic Society Assembly on Sleep and Respiratory Neurobiology. The role of weight management in the treatment of adult obstructive sleep apnea. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med 198(6):e70–e87. CrossRefPubMedGoogle Scholar

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© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Otorhinolaryngology Head and Neck Surgery, Beijing Shijitan HospitalCapital Medical UniversityBeijingChina

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