Correlation between TIM-3 expression on peripheral blood NK cells and pregnancy outcome in patients with gestational diabetes mellitus
陈薇 1王琛琛 1章杨韦 1丁其培 1徐晓英1
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作者信息
1. 海安市人民医院妇产科，海安 226600
折叠
摘要
目的 探究妊娠期糖尿病(gestational diabetes mellitus，GDM)患者外周血自然杀伤(natural killer，NK)细胞中T细胞免疫球蛋白黏蛋白-3(T cell immunoglobulin mucin domain containing molecules-3，TIM-3)表达与妊娠结局的相关性。 方法 选取于海安市人民医院2019年6月至2022年6月确诊为妊娠期糖尿病的孕妇52例作为研究组，并抽取同期于我院住院分娩的健康孕妇41例作为对照组。采集两组患者清晨空腹外周血，采用密度梯度离心法分离外周血单个核细胞(peripheral blood mononuclear cell，PBMC)；采用流式细胞仪检测所有患者外周血CD56＋ CD16- NK细胞表达及TIM-3在NK细胞中的表达。采用Spearman相关分析对外周血CD56＋CD16－ NK细胞表达及TIM-3在NK细胞中表达与孕妇妊娠结局的相关性。 结果 研究组孕期口服糖耐量试验(oral glucose tolerance test，OGTT)血糖水平空腹时、服糖后1及2 h时均明显高于对照组[mmol/L：(5.73±0.87)比(4.65±0.59)；(11.58±3.85)比(8.76±1.79)；(10.53±2.84)比(7.03±1.12)；t值分别为6.81、4.33、7.44，P值均<0.05]；且妊娠不良结局孕妇明显多于对照组，差异均有统计学意义[34.62%比7.32%，t＝9.77，P<0.05]。流式细胞术检测结果显示，研究组孕妇外周血CD56＋ CD16－ NK细胞表达及TIM-3在NK细胞中表达均明显低于对照组，差异有统计学意义[%：(35.44±2.58)比(78.62±8.45)；(21.33±1.63)比(70.22±7.57)；t值分别为34.89、45.32，P值<0.05]。不良组孕期OGTT血糖水平空腹时、服糖后1及2 h时均明显高于良好组，差异有统计学意义[mmol/L：(6.23±0.85)比(5.25±0.61)，(12.53±3.96)比(10.56±2.61)，(11.42±3.22)比(9.35±1.52)，t值分别为4.80、2.16、3.16，P值均<0.05)]。研究组中不良组孕妇外周血CD56＋ CD16－ NK细胞表达及TIM-3在NK细胞中表达均明显低于良好组，差异有统计学意义[%：(25.86±2.15)比(40.35±3.57)，(16.48±1.24)比(23.68±2.32)；t值分别为15.73，12.24，P值均<0.05]。Spearman分析结果显示，外周血CD56＋ CD16－ NK细胞表达与孕妇良好妊娠结局、TIM-3表达与孕妇良好妊娠结局均呈显著正相关，差异有统计学意义(r＝0.62、0.58，P值均<0.05)。 结论 GDM孕妇外周血CD56＋CD16－ NK细胞表达及TIM-3表达均明显降低，并且与孕妇良好妊娠结局呈正相关，外周血CD56＋CD16－ NK细胞表达及TIM-3表达越低GDM孕妇出现不良妊娠结局的可能性越大，提示外周血NK细胞TIM-3表达可作为预测GDM孕妇妊娠结局的参考指标。 Objective To explore the correlation between T cell immunoglobulin domain and mucin domain-3 (TIM-3) expression on peripheral blood natural killer (NK) cells and pregnancy outcome in patients with gestational diabetes mellitus (GDM). Methods A total of 52 GDM cases in Hai'an People's Hospital from June 2019 to June 2022 were selected as study group, and another 41 healthy pregnant women were concurrently enrolled as control group. Milliliters of fasting blood samples were collected. Peripheral blood mononuclear cell(PBMC) were isolated by centrifugation over Ficoll gradient density. Flow cytometry was utilized to detect the expression of CD56+ CD16- NK cells in peripheral blood and the expression of TIM-3 on NK cells. Spearman correlation analysis was performed to discuss the correlation of peripheral blood CD56+ CD16- NK cells expression and TIM-3 expression on NK cells with the maternal pregnancy outcome in GDM. Results The oral glucose tolerance test(OGTT) blood glucose levels during pregnancy in the study group were significantly higher than those in the control group at fasting and 1 and 2 hours after glucose administration[mmol/L: (5.73±0.87)vs(4.65±0.59), (11.58±3.85)vs(8.76±1.79), (10.53±2.84)vs(7.03±1.12) t values are 6.81, 4.33 and 7.44, respectively, , all P values<0.05] Moreover, the number of pregnant women with adverse pregnancy outcomes was significantly higher than that of the control group, and the differences were statistically significant(34.62 vs 7.32%,t=9.77, P<0.05). The results of flow cytometry showed that the expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the control group, with statistical significance[%: (35.44±2.58)vs(78.62±8.45), (21.33±1.63)vs(70.22±7.57) t values are 34.89 and 45.32, both P value <0.05)]. The OGTT blood glucose levels during pregnancy in the poor group were significantly higher than those in the good group at fasting, 1 hour and 2 hours after glucose administration, with statistical significance[mmol/L: (6.23±0.85)vs(5.25±0.61), (12.53±3.96)vs(10.56±2.61), (11.42±3.22)vs(9.35±1.52), t values are 4.80, 2.16 and 3.16, respectively, all P values<0.05)]. The expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the good group, with statistical significance[%: (25.86±2.15)vs(40.35±3.57), (16.48±1.24)vs(23.68±2.32) tvalues are 15.73, 12.24, both P values<0.05]. Spearman correlation analysis denoted that both the peripheral blood CD56+ CD16-NK cell expression and the TIM-3 expression were positively correlated with good pregnancy outcome(r=0.62, 0.58, both P values <0.05). Conclusion The peripheral blood CD56+ CD16- NK cell expression and TIM-3 expression are notably down-regulated in GDM women, and are positively correlated with good pregnancy outcome, suggesting that women with lower expression of CD56+ CD16- NK cell and TIM-3 suffer a greater risk of adverse pregnancy outcome, so the TIM-3 expression on peripheral blood NK cells can be used as a reference index to predict the pregnancy outcome of GDM women.
Abstract
Objective To explore the correlation between T cell immunoglobulin domain and mucin domain-3 (TIM-3) expression on peripheral blood natural killer (NK) cells and pregnancy outcome in patients with gestational diabetes mellitus (GDM). Methods A total of 52 GDM cases in Hai'an People's Hospital from June 2019 to June 2022 were selected as study group, and another 41 healthy pregnant women were concurrently enrolled as control group. Milliliters of fasting blood samples were collected. Peripheral blood mononuclear cell(PBMC) were isolated by centrifugation over Ficoll gradient density. Flow cytometry was utilized to detect the expression of CD56+ CD16- NK cells in peripheral blood and the expression of TIM-3 on NK cells. Spearman correlation analysis was performed to discuss the correlation of peripheral blood CD56+ CD16- NK cells expression and TIM-3 expression on NK cells with the maternal pregnancy outcome in GDM. Results The oral glucose tolerance test(OGTT) blood glucose levels during pregnancy in the study group were significantly higher than those in the control group at fasting and 1 and 2 hours after glucose administration[mmol/L: (5.73±0.87)vs(4.65±0.59), (11.58±3.85)vs(8.76±1.79), (10.53±2.84)vs(7.03±1.12) t values are 6.81, 4.33 and 7.44, respectively, , all P values<0.05] Moreover, the number of pregnant women with adverse pregnancy outcomes was significantly higher than that of the control group, and the differences were statistically significant(34.62 vs 7.32%,t=9.77, P<0.05). The results of flow cytometry showed that the expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the control group, with statistical significance[%: (35.44±2.58)vs(78.62±8.45), (21.33±1.63)vs(70.22±7.57) t values are 34.89 and 45.32, both P value <0.05)]. The OGTT blood glucose levels during pregnancy in the poor group were significantly higher than those in the good group at fasting, 1 hour and 2 hours after glucose administration, with statistical significance[mmol/L: (6.23±0.85)vs(5.25±0.61), (12.53±3.96)vs(10.56±2.61), (11.42±3.22)vs(9.35±1.52), t values are 4.80, 2.16 and 3.16, respectively, all P values<0.05)]. The expression of CD56+ CD16 NK cells and TIM-3 in NK cells in the peripheral blood of pregnant women in the study group were significantly lower than those in the good group, with statistical significance[%: (25.86±2.15)vs(40.35±3.57), (16.48±1.24)vs(23.68±2.32) tvalues are 15.73, 12.24, both P values<0.05]. Spearman correlation analysis denoted that both the peripheral blood CD56+ CD16-NK cell expression and the TIM-3 expression were positively correlated with good pregnancy outcome(r=0.62, 0.58, both P values <0.05). Conclusion The peripheral blood CD56+ CD16- NK cell expression and TIM-3 expression are notably down-regulated in GDM women, and are positively correlated with good pregnancy outcome, suggesting that women with lower expression of CD56+ CD16- NK cell and TIM-3 suffer a greater risk of adverse pregnancy outcome, so the TIM-3 expression on peripheral blood NK cells can be used as a reference index to predict the pregnancy outcome of GDM women.
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