肾移植后慢性抗体介导排斥反应患者外周血树突状细胞表型特征研究  

Phenotypic analysis of dendritic cells in patients with chronic antibody-mediated rejection after kidney transplantation

作　　者：罗俐梅[1] 樊吉文 冯伟华[1] 严琳[1] 欧晓琪 台蕴泽 李壹[1] Luo Limei;Fan Jiwen;Feng Weihua;Yan Lin;Ou Xiaoqi;Tai Yunze;Li Yi(Department of laboratory medicine,West China hospital of Sichuan university,Chengdu 610041,China)

机构地区：[1]四川大学华西医院实验医学科,成都610041

出　　处：《中华检验医学杂志》2024年第12期1459-1464,共6页Chinese Journal of Laboratory Medicine

基　　金：国家自然科学基金项目(82102466,82472346);四川省科技厅重点研发计划(2024NSFSC1540,2023YFS0108)。

摘　　要：目的探讨肾移植后慢性抗体介导排斥反应(CAMR)患者外周血中树突状细胞的表型特征, 揭示其在CAMR发生与发展中的潜在作用机制。方法病例对照研究。共纳入2020年10月1日至2021年7月31日在四川大学华西医院接受肾移植手术或长期随访的肾移植受者25例, 其中CAMR患者15例, 肾功能稳定组患者10例。采用流式细胞术分析外周血单个核细胞中DC亚群, 采用相关性分析探讨各DC亚群与肾功能检验指标之间的关系, 并在CAMR组中基于DC绝对计数、ILT3+mDC绝对计数、ILT3+pDC绝对计数、ILT4+mDC+绝对计数以及ILT4+pDC绝对计数结果进行迭代聚类分析。结果与肾功能稳定组患者相比, CAMR组患者pDC百分比和绝对计数、pDC/mDC比值、ILT3+pDC绝对计数均降低, 而ILT3+mDC百分比升高, DC百分比与Scr(r=-0.467, P=0.019)和CysC(r=-0.502, P=0.011)呈负相关, 与eGFR呈正相关(r=0.436, P=0.029), 而ILT4+pDC百分比与CysC呈正相关(r=0.433, P=0.031), DC绝对计数与CysC呈负相关(r=-0.425, P=0.034)。CAMR组的迭代聚类分析定义了两组患者, 两组患者的Scr、eGFR以及CysC检测结果差异均有统计学意义。结论移植后患者DC亚群的分布及ILT3和ILT4的表达, 可能为早期识别CAMR风险、优化免疫抑制治疗策略提供新的生物标志物。特别是pDC的变化及ILT3、ILT4的表达水平, 可作为评估移植后免疫状态和肾功能预后的有价值指标。Objective:To investigate the phenotypic characteristics of dendritic cell(DC)in the peripheral blood of patients with chronic antibody-mediated rejection(CAMR)after kidney transplantation,revealing the potential role of DCs in the occurrence and development of CAMR.Methods:Case-control study.A total of 25 kidney transplant recipients who underwent kidney transplantation or were under long-term follow-up at West China Hospital of Sichuan University from October 1st,2020,to July 31st,2021,were recruited in this case-control study,comprising 15 cases of patients with CAMR and 10 cases of patients with stable renal function.Flow cytometry was used to analyze DC subsets in peripheral blood mononuclear cells(PBMC)of patients.Correlation analysis was conducted to explore the relationship between DC subsets and renal function indicators.Iterative cluster analysis was performed based on the absolute counts of DC,ILT3+mDC,ILT3+pDC,ILT4+mDC and ILT4+pDC in the CAMR group.Results:Compared with the stable renal function group,the percentages and absolute count of pDC,pDC/mDC ratio,and absolute count of ILT3+pDC were decreased while percentages of ILT3+mDC were increased in CAMR group.DC percentage was negatively correlated with Scr(r=-0.467,P=0.019)and CysC(r=-0.502,P=0.011)and positively correlated with eGFR(r=0.436,P=0.029).ILT4+pDC percentage was positively correlated with CysC(r=0.433,P=0.031),and absolute count of DCs was negatively correlated with CysC(r=-0.425,P=0.034).Iterative cluster analysis defined two patient clusters with significant statistic differences of Scr,eGFR,and CysC detection results in the CAMR group.Conclusion:The distribution of DC subsets and the expression of ILT3 and ILT4 in the blood of post-transplant patients could provide new biomarkers for early identification of CAMR risk and optimization of immunosuppressive therapy strategies.Particularly,changes of pDC and the expression levels of ILT3,ILT4 can serve as valuable indicators for assessing post-transplant immune status and renal function pr

关 键 词：抗体介导排斥反应 慢性排斥反应 树突状细胞 ILT3 ILT4 肾移植 

分 类 号：R699.2[医药卫生—泌尿科学]