PD-1/PDL-1在原因不明复发性流产患者T细胞、Tregs和Bregs细胞中的表达及意义  

Expression and significance of PD-1/PDL-1 in T cells,Treg and Breg cells of patients with unexplained recurrent abortion

作　　者：陈葆国 干军 郑瑞 章卫国 俞依妮 Chen Baoguo;Gan Jun;Zheng Rui;Zhang Weiguo;Yu Yini(Central Laboratory,Department of Hematology of Affiliated Taizhou Hospital,Wenzhou Medical College,Linhai317000,China)

机构地区：[1]温州医科大学附属台州医院中心实验室,临海317000

出　　处：《中华检验医学杂志》2024年第6期678-685,共8页Chinese Journal of Laboratory Medicine

基　　金：浙江省卫生健康科技计划(2021ky1196)。

摘　　要：目的探讨程序性死亡因子1(PD-1)/程序性死亡因子配体1(PDL-1)在原因不明复发性流产(URSA)患者T细胞、调节性T细胞(Tregs)、调节性B细胞(Bregs)中的表达及意义。方法收集2020年2月至2022年2月在温州医科大学附属台州医院就诊的42例URSA患者为患者组,34名健康孕妇(正常妊娠组)和30名未孕健康体检者(对照组),进行回顾性分析。采用流式细胞术检测外周血PD-1/PDL-1在Tregs细胞、Bregs细胞和[T细胞、B细胞和自然杀伤细胞(TBNK)]淋巴细胞亚群中的表达,以及血清辅助T细胞1[γ干扰素(IFN-γ)、α肿瘤坏死因子(TNF-α)]Th1/辅助T细胞2[白介素4(IL-4)、IL-6和IL-10]Th2/辅助T细胞17(IL-17)Th17细胞因子表达水平。对患者进行淋巴细胞免疫治疗,治疗结束检测患者PD-1/PD-L1水平变化及随访记录妊娠结局。多组间比较用方差分析,URSA患者治疗前后比较用配对t检验,各检测指标相关性用双变量相关分析法。结果PD-1/PDL-1在URSA患者组外周血Tregs、Bregs细胞和T淋巴细胞亚群中的表达显著低于正常妊娠组,差异有统计学意义(均P<0.01)。PD-1/PDL-1在白细胞分化抗原4(CD4+)T细胞中的表达与血清Th1细胞因子IFN-γ、TNF-α表达水平呈负相关(r=‒0.44、‒0.85、‒0.33、‒0.94,均P<0.01);PD-1/PDL-1在CD4+T细胞中的表达与血清Th2细胞因子白细胞介素4(IL-4)、IL-6和IL-10表达水平呈正相关(r=0.55、0.47、0.41、0.33、0.46、0.69,均P<0.01)。Bregs细胞比例、Tregs细胞比例与血清IL-10表达水平呈正相关(r=0.97、0.95,均P<0.01)。Tregs细胞比例与IL-17表达水平呈负相关(r=‒0.95,P<0.01)。PD-1/PDL-1在Bregs细胞及Tregs细胞中的表达与血清IL-10表达水平呈正相关(r=0.95、0.36、0.96、0.95,均P<0.01)。血清IL-10表达水平与IL-17表达水平呈负相关(r=‒0.58,P<0.01)。URSA治疗后妊娠成功23例,失败19例。USRA治疗成功组PD-1/PD-L1在CD4、CD8、Tregs细胞和Bregs细胞上的表达高于治疗前,差异有统计�Objective To explore the expression levels and significance of programmed death factor 1(PD-1)/programmed death factor ligand 1(PDL-1)in T cells,regulatory T cells(Tregs),and regulatory B cells(Bregs)in patients with unexplained recurrent spontaneous abortion(URSA).Methods Forty-two URSA patients(as patient group),34 healthy pregnant women(as normal pregnancy group)and 30 unpregnant healthy examination patients(as control group)were collected for retrospective analysis,all study subjects were from patients who were treated in Taizhou Hospital affiliated to Wenzhou Medical University from February 2020 to February 2022.Flow cytometry was used to detect the expression level of PD-1/PDL-1 in Treg cells,Breg cells and[T cells,B cells and natural killer cells(TBNK)]lymphocyte subsets,as well as the expression level of serum Th1(IFN-γ,TNF-α)/Th2(IL-4,IL-6,IL-10)/Th17(IL-17)cytokine expression.The patients were treated with lymphocyte immunotherapy,the changes of PD-1/PDL-1 levels were detected at the end of treatment,and the pregnancy outcome was recorded during follow-up.Comparisons between multiple groups were performed by ANOVA,comparisons before and after treatment in URSA patients were performed by paired T-test,and correlation of each test index by bivariate correlation analysis.Results The expression levels of PD-1/PDL-1 in Treg,Breg cells and T lymphocyte subsets in peripheral blood of patients with URSA was significantly lower than that of healthy pregnant women(all P<0.01).The expression level of PD-1/PDL-1 in CD4+T cells was negatively correlated with the expression of serum Th1 cytokines Interferon gamma(IFN-γ)and tumor necrosis factor alpha(TNF-α)(The r values were-0.44,-0.85,-0.33,and-0.94,respectively,all P<0.01).The expression level of PD-1/PDL-1 in CD4+T cells was positively correlated with the expression of serum Th2 cytokines interleukin 4(IL-4),interleukin 6(IL-6)and interleukin 10(IL-10)(The r values were 0.55,0.47,0.41,0.33,0.46,and 0.69,respectively,all P<0.01).The proportion of Breg cells an

关 键 词：复发性流产 程序性死亡因子1 程序性死亡因子配体1 调节性B细胞 调节性T细胞 

分 类 号：R714.21[医药卫生—妇产科学]