CCL11和sTNFR2作为原因不明复发性流产患者淋巴细胞免疫治疗潜在生物标志物的探讨  

Exploration of CCL11 and sTNFR2 as potential biomarkers for the efficacy of lymphocyte immunotherapy in women with unexplained recurrent spontaneous abortion

作　　者：李莉[1] 王海燕[1] 乔杰[1] 李蓉[1] 刘平[1] Li Li;Wang Haiyan;Qiao Jie;Li Rong;Liu Ping(Department of Obstetrics and Gynecology,Center for Reproductive Medicine,Peking University Third Hospital,State Key Laboratory of Female Fertility Promotion,National Clinical Research Center for Obstetric and Gynecologic Diseases,Key Laboratory of Assisted Reproduction,Ministry of Education,Beijing100191,China)

机构地区：[1]北京大学第三医院妇产科生殖医学中心,女性生育力促进全国重点实验室,国家妇产疾病临床医学研究中心,辅助生殖教育部重点实验室,北京100191

出　　处：《中华妇产科杂志》2025年第1期24-33,共10页Chinese Journal of Obstetrics and Gynecology

基　　金：北京大学第三医院院队列建设项目(BYSYDL2022003);首都卫生发展科研专项(首发2024-1-4093)。

摘　　要：目的探寻淋巴细胞免疫治疗(LIT)治疗原因不明复发性流产(URSA)的生物标志物。方法收集2014年12月至2015年6月在北京大学第三医院接受LIT的URSA患者24例的血清,采用含有40种细胞因子的半定量双抗夹心法抗体芯片进行检测,对URSA患者LIT前后外周血中的免疫相关细胞因子进行筛选,再应用微球流式多因子定量检测技术进行验证检测。24例患者根据LIT后最终的妊娠结局分为足月分娩组(15例)和流产组(9例),应用线性回归分析目标因子变化与妊娠结局之间的关系。结果半定量抗体芯片筛选发现,所有被纳入的24例URSA患者中,白细胞介素15(IL-15)、干扰素诱导的单核因子(MIG)、CC型趋化因子配体(CCL)1的荧光信号值在LIT治疗后显著低于治疗前(P均<0.05);在足月分娩组,IL-15、CCL1、巨噬细胞炎性蛋白(MIP)1α的荧光信号值在LIT治疗后显著低于治疗前(P均<0.05);流产组中,MIG和MIP-1δ的荧光信号值在LIT治疗后显著低于治疗前(P均<0.05);线性回归分析显示,LIT治疗后足月分娩组的CCL11的荧光信号值增加(P=0.012),可溶性肿瘤坏死因子受体2(sTNFR2)的荧光信号值降低(P=0.029)。微球流式多因子定量检测技术验证结果显示,经线性回归分析,LIT后足月分娩组患者CCL11水平显著升高(P=0.001),sTNFR2的水平显著降低(P=0.001)。结论CCL11和sTNFR2可能是潜在的生物标志物,可能预测URSA患者LIT后的妊娠结局。ObjectiveTo explore biomarkers for the efficacy of lymphocyte immunotherapy(LIT)treating women with unexplained recurrent spontaneous abortion(URSA).MethodsSerum samples from 24 URSA potients who received LIT were collected at Peking University Third Hospital from December 2014 to June 2015.Semiquantitative sandwich-based antibody arrays containing 40 cytokines were used to screen target immune cytokines in the peripheral blood of URSA patients before and after LIT.Multifactor quantitative microsphere flow cytometry detection validated the levels of target cytokines.Based on the final pregnancy outcome after LIT,24 URSA patients were divided into the full-term delivery group(15 cases)and the abortion group(9 cases).Furthermore,linear regression analysis were applied to evaluate the relationship between target cytokines and pregnancy outcomes.ResultsSemiquantitative sandwich-based antibody arrays suggested that,among all 24 URSA patients included in this study,the intensities of the fluorescence signal were significantly lower post-LIT versus pre-LIT for the following cytokines:interleukin-15(IL-15),monokine induced byγ-interferon(MIG),C-C motif chemokine ligand(CCL)1(all P<0.05).In the full-term delivery group,the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines:IL-15,CCL1,macrophage inflammatory protein(MIP)1α(all P<0.05).In the abortion group,the intensities of the fluorescence signal post-LIT were significantly lower than pre-LIT for the following cytokines:MIG,MIP-1δ(all P<0.05).Linear regression analysis showed that the intensity of the fluorescence signal of CCL11 was increased and the intensity of the fluorescence signal of soluble tumor necrosis factor receptor 2(sTNFR2)was decreased in the full-term delivery group after LIT,the differences were statistically significant(P=0.012,0.029).Validation results of multifactor quantitative microsphere flow cytometry detection showed that the level of CCL11 was significantly increased(P=0.001)and

关 键 词：流产 习惯性 淋巴细胞输注 免疫疗法 细胞因子类 趋化因子CCL11 受体 肿瘤坏死因子 Ⅱ型 生物标记 

分 类 号：R714.21[医药卫生—妇产科学]