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睡眠呼吸暂停中的不变自然杀伤T细胞缺陷与功能损害:与癌症合并症的关联。

Invariant Natural Killer T Cell Deficiency and Functional Impairment in Sleep Apnea: Links to Cancer Comorbidity.

作者信息

Gaoatswe Gadintshware, Kent Brian D, Corrigan Michelle A, Nolan Geraldine, Hogan Andrew E, McNicholas Walter T, O'Shea Donal

机构信息

Obesity Immunology Group, Education & Research Center, St Vincent's University Hospital, University College Dublin, Dublin, Ireland.

Pulmonary and Sleep Disorders Unit, St Vincent's University Hospital, Dublin, and School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland.

出版信息

Sleep. 2015 Oct 1;38(10):1629-34. doi: 10.5665/sleep.5062.

DOI:10.5665/sleep.5062
PMID:26414901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4576337/
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.

摘要

研究目的

新出现的证据表明阻塞性睡眠呼吸暂停(OSA)与癌症发病率和死亡率增加有关。不变自然杀伤T(iNKT)细胞在癌症免疫中起重要作用。我们假设OSA患者循环中不变自然杀伤T(iNKT)细胞数量低,且其功能可能也受损。本研究旨在评估OSA患者循环中iNKT细胞的频率。

设计

我们通过流式细胞术评估了33名因可能患有OSA而接受评估的打鼾者循环中iNKT细胞的频率。使用iNKT细胞系,我们还评估了24小时暴露于低氧对细胞凋亡、细胞毒性和细胞因子产生的影响。

地点

教学医院的睡眠单元和研究实验室。

患者

评估了33名打鼾者:9名无OSA(呼吸暂停低通气频率[AHI]<5次/小时),12名轻度至中度OSA(AHI 5 - 30),12名重度OSA(AHI>30)。

测量与结果

与轻度至中度(0.24%)或无OSA(0.35%)的患者相比,重度OSA患者的iNKT细胞明显更少(0.18%),P = 0.0026。iNKT细胞频率与呼吸暂停低通气指数(r = -0.58,P = 0.001)、氧饱和度下降指数(r = -0.58,P = 0.0003)以及SpO2%<90%(r = -0.5407,P = 0.005)呈负相关。持续气道正压通气(nCPAP)治疗12个月后,iNKT细胞频率增加(P = 0.015)。低氧导致细胞凋亡增加(P = 0.016)和细胞毒性受损(P = 0.035)。

结论

阻塞性睡眠呼吸暂停(OSA)患者循环中不变自然杀伤T(iNKT)细胞水平显著降低,低氧导致iNKT细胞功能受损。这些观察结果可能部分解释了OSA患者报告的癌症风险增加。

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