allo-HSCT后淋巴细胞亚群重建与GVHD及感染的相关性  

Association of lymphocyte subset reconstitution with graft-versus-host disease and infection after allogenic hematopoietic stem cell transplantation

作　　者：王淑惠 慕莹 韩洁 魏晓芳[1] 刘秋媛 阎丽平[1] WANG Shuhui;MU Ying;HAN Jie;WEI Xiaofang;LIU Qiuyuan;YAN Liping(Department of Clinical Laboratory,The Affiliated Qingdao Central Hospital of Qingdao University,Qingdao 266042,China)

机构地区：[1]青岛大学附属青岛市中心医院检验科,山东青岛266042 [2]青岛大学附属青岛市中心医院血液科,山东青岛266042

出　　处：《青岛大学学报（医学版）》2024年第2期213-217,共5页Journal of Qingdao University(Medical Sciences)

基　　金：山东省自然科学基金青年项目(ZR2022QH269)。

摘　　要：目的探讨血液病病人异基因造血干细胞移植(allo-HSCT)后外周血淋巴细胞各亚群的重建规律,以及淋巴细胞各亚群变化与移植后移植物抗宿主病(GVHD)及感染的关系。方法采用流式细胞术,检测32例allo-HSCT病人清髓处理前3 d和移植后14、30、90、180、365、730 d时的淋巴细胞亚群分布情况,并分析病人GVHD以及感染与淋巴细胞各亚群变化的关系。结果与移植前比较,血液病病人移植后总淋巴细胞、CD3^(+)T细胞、CD4^(+)T细胞、CD8^(+)T细胞、CD16^(+)CD56^(+)NK细胞、CD19^(+)B细胞重建的速度不同,其中NK细胞恢复最快,不到30 d就恢复至移植前水平;其次为CD8^(+)T细胞,约30 d恢复至移植前水平;CD3^(+)T细胞在移植后60 d基本可以达到移植前水平;而B细胞以及CD4^(+)T细胞恢复较慢,B细胞约360 d恢复至移植前水平,CD4^(+)T细胞在移植后730 d仍未恢复到移植前水平。移植后第90天,发生急性移植物抗宿主病(aGVHD)病人5例,其CD3^(+)T细胞(t’=3.334,P<0.05)、CD4^(+)T细胞(t=3.836,P<0.05)和CD16^(+)CD56^(+)NK细胞(t=3.300,P<0.05)绝对计数均低于非急性移植物抗宿主病(non-aGVHD)组,差异有统计学意义。移植后第365天,发生慢性移植物抗宿主病(cGVHD)病人17例,其CD4^(+)T细胞计数低于非慢性移植物抗宿主病(non-cGVHD)组,差异有统计学意义(t=2.918,P<0.05)。与无感染组(n=5)比较,移植后第180天病毒感染组(n=6)淋巴细胞(t=2.441,P<0.05)、CD4^(+)T细胞(t=3.513,P<0.05)、NK细胞(t=3.728,P<0.05)、B细胞(t=2.937,P<0.05)降低;细菌感染组(n=8)淋巴细胞(t=2.535,P<0.05)、CD4^(+)T细胞(t’=6.726,P<0.05)降低,CD8^(+)T细胞升高(t’=-2.945,P<0.05);真菌感染组(n=4)CD4^(+)T细胞降低(t=2.579,P<0.05),CD8^(+)T细胞升高(t=2.423,P<0.05);混合感染组(n=9)淋巴细胞(t=2.195,P<0.05)、CD3^(+)T细胞(t=2.649,P<0.05)、CD4^(+)T细胞(t=3.728,P<0.05)、CD8^(+)T细胞(t=2.579,P<0.05)、B细胞(t=3.045,P<0.05)和NK细胞(t=2.207,P<0.05)绝对计数均降低。Objective To investigate the reconstitution of lymphocyte subsets in peripheral blood and the relationship between lymphocyte subset changes and graft-versus-host disease(GVHD)and infection after allogeneic hematopoietic stem cell transplantation(allo-HSCT)in patients with malignant hematologic diseases.Methods Thirty-two patients undergoing allo-HSCT were examined using flow cytometry for the distribution of lymphocyte subsets 3 d before myeloablative conditioning and 14,30,90,180,365,and 730 d after transplantation.The relationship between lymphocyte subset changes and GVHD and infection was analyzed.Results After transplantation,the reconstitution speed of total lymphocytes,CD3^(+)T cells,CD4^(+)T cells,CD8^(+)T cells,CD16^(+)CD56^(+)NK cells,and CD19^(+)B cells differed:NK cells recovered first to the pre-transplant level within 30 d;CD8^(+)T cells around 30 d after transplantation;CD3^(+)T cells around 60 d after transplantation;B lymphocytes around 360 d after transplantation;but CD4^(+)T cells did not recover to the pre-transplant level 730 d after transplantation.On the 90th day after transplantation,5 patients had acute GVHD,whose absolute counts of CD3^(+)T cells(t’=3.334,P<0.05),CD4^(+)T cells(t=3.836,P<0.05),and CD16^(+)CD56^(+)NK cells(t=3.300,P<0.05)were significantly lower compared with those without acute GVHD.On the 365th day after transplantation,17 patients had chronic GVHD,whose CD4^(+)T cell count was significantly lower compared with those without chronic GVHD(t=2.918,P<0.05).On the 180th day after transplantation,compared with the non-infection group(n=5),the viral infection group(n=6)showed significantly decreased levels of lymphocytes(t=2.441,P<0.05),CD4^(+)T cells(t=3.513,P<0.05),NK cells(t=3.728,P<0.05),and B cells(t=2.937,P<0.05);the bacterial infection group(n=8)showed significantly decreased levels of lymphocytes(t=2.535,P<0.05)and CD4^(+)T cells(t’=6.726,P<0.05)and significantly increased levels of CD8^(+)T cells(t’=-2.945,P<0.05);the fungal infection group(n=4)showed signific

关 键 词：造血干细胞移植 淋巴细胞亚群 移植物抗宿主病 感染 

分 类 号：R392.4[医药卫生—免疫学] R457[医药卫生—基础医学]