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Title: [The expressions of CTLA-4 and PD-1 on CD(4)(+) T cells and the level of plasma VEGF in patients with obstructive sleep apnea hypopnea syndrome].
Author: Liu YL, Luo SH, Ou Q, Yuan P, Lu MZ, Chen JN, Luo ZR, Lao MC, Cui JH, Gao XL.
Journal: Zhonghua Jie He He Hu Xi Za Zhi; 2019 Apr 12; 42(4):268-274. PubMed ID: 30955284.
Abstract:
Objective: CD(4)(+)T cells, cytotoxic T-lymphocyte antigen 4 (CTLA-4), programmed cell death-1 (PD-1) and vascular endothelial growth factor (VEGF) are associated with cancer development. The aim of the present study was to investigate the expression of CTLA-4, PD-1 and VEGF in patients with obstructive sleep apnea hypopnea syndrome (OSAHS). Methods: From January 2017 to January 2018, a total of 47 first-visit outpatients were recruited in the Sleep and Respiratory Disorder Center of Guangdong Provincial People's Hospital, and were divided into control group (N=17, mean age 54±12 years), mild-to-moderate OSAHS group (N=15, mean age 54±12 years) and severe OSAHS group (N=15, mean age 56±13 years). Venous blood was collected, plasma and cells were isolated, the expressions of PD-1 and CTLA-4 on the surface of CD(4)(+)T cells were detected by flow cytometry, and plasma VEGF was measured by enzyme linked immunosorbent assay. Results: The proportion of CD(4)(+)T cells in control group, mild-to-moderate OSAHS group and severe OSAHS group were respectively(38±8)%, (35±8)% and (38±6)% (F=1.228, P>0.05). The expression of CTLA-4 on CD(4)(+)T cells were respectively [1.13 (0.59~1.78)]%, [0.45 (0.16~1.43)]% and [0.87(0.47~1.46)]% (H=2.205, P>0.05). The expression of PD-1 on CD(4)(+)T cells were respectively [4.24 (2.12~6.03)]%, [3.54(2.69~5.09)]% and [3.31(1.67~8.25)]% (H=0.541, P>0.05). The concentrations of VEGF in control group, mild-to-moderate OSAHS group and severe OSAHS group were statistically different [(395.16±87.78) ng/L vs (452.85±107.97) ng/L vs (546.42±199.27) ng/L, F=4.827, P=0.013]. Compared with the control group, VEGF concentration was significantly increased in the severe OSAHS group(P<0.01). VEGF concentration was correlated negatively with the lowest SpO(2) (r (s)=-0.480,P=0.001), but positively with apnea-hypopnea index(r (s)=0.403, P=0.005), oxygen desaturation index (r (s)=0.378, P=0.010) and proportion of SpO(2) less than or equal to 90% of total sleep time(r (s)=0.547, P=0.000 3). Conclusion: There was no significant difference of PD-1 and CTLA-4 expression on CD(4)(+)T cells in patients with and without OSAHS. The expression of VEGF was elevated in OSAHS patients, and increased with the severity of OSAHS and hypoxia. 目的： 探讨与肿瘤发生发展相关的CD(4)(+) T细胞、细胞毒性T淋巴细胞相关抗原-4（cytotoxic T-lymphocyte antigen 4，CTLA-4）、程序性死亡蛋白-1（programmed cell death-1，PD-1）及血管内皮生长因子（vascular endothelial growth factor，VEGF）在阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者中的变化。 方法： 纳入2017年1月至2018年1月广东省人民医院睡眠呼吸障碍中心的首诊患者47例，根据多导睡眠监测（PSG）检查结果分为对照组、轻中度OSAHS组及重度OSAHS组，其中对照组17例，男10例，女7例，平均年龄（54±12）岁；轻中度OSAHS组15例，男9例，女6例，平均年龄（54±12）岁；重度OSAHS组15例，男10例，女5例，平均年龄（56±13）岁。采集静脉血，分离血浆及细胞，使用流式细胞术检测外周血CD(4)(+) T细胞表面PD-1和CTLA-4的表达，用酶联免疫吸附实验测定血浆VEGF的浓度。 结果： 对照组、轻中度OSAHS组及重度OSAHS组CD(4)(+) T细胞比例分别为（38±8）%、（35±8）%和（38±6）%（F=1.228，P>0.05），CD(4)(+) T细胞CTLA-4的表达分别为1.13%（0.59%~1.78%）、0.45%（0.16%~1.43%）和0.87%（0.47%~1.46%），差异无统计学意义（H=2.205，P>0.05），CD(4)(+) T细胞PD-1的表达分别为4.24%（2.12%~6.03%）、3.54%（2.69%~5.09%）和3.31%（1.67%~8.25%），差异无统计学意义（H=0.541，P>0.05）。对照组、轻中度OSAHS组及重度OSAHS组外周血VEGF浓度分别为（395±88）、（453±108）及（546±199）ng/L，差异有统计学意义（F=4.827，P=0.013），重度OSAHS组明显高于对照组（P<0.01）。VEGF浓度与夜间最低SpO(2)呈负相关（r(s)=-0.480，P=0.001），与AHI（r(s)=0.403，P=0.005）、ODI（r(s)=0.378，P=0.010）、SpO(2)≤90%（%TST）（r(s)=0.547，P=0.000 3）均呈正相关。 结论： OSAHS患者CD(4)(+) T细胞PD-1及CTLA-4的表达无显著变化，但有下降趋势；VEGF表达上调，且随着严重程度和夜间缺氧程度加重而增高。.

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