异基因造血干细胞移植后细胞免疫重建与真菌感染的相关性

doi:10.3969/j.issn.1673-8640.2020.05.011

摘要/Abstract

摘要：

目的探讨血液恶性肿瘤患者异基因造血干细胞移植（allo-HSCT）后CD4⁺T细胞免疫重建及其与侵袭性真菌感染（IFI）的关系。方法选取2010年2月—2014年10月滨州医学院附属医院行allo-HSCT的血液恶性肿瘤患者47例,以同期体检健康者40名作为对照组。分别于移植后1、2、3个月采用流式细胞术检测患者移植后免疫细胞亚群数,采用酶联免疫吸附试验（ELISA）检测细胞因子浓度。观察患者移植后IFI发生情况,及其与CD4⁺T细胞免疫重建的相关性。结果移植后CD4⁺T细胞及其免疫细胞亚群数随时间递增,但移植后3个月免疫细胞亚群数仍低于对照组;与对照组比较,移植后白细胞介素（IL）-6和IL-10水平升高,转化生长因子（TGF）-β水平降低;IFI发生率为19.15%（9/47）。多因素Logistic回归分析结果显示,IFI可能与辅助性T细胞（Th）17的细胞数有关,而与Th1、Th2、调节性T细胞细胞数以及IL-6、IL-10、TGF-β和干扰素（IFN）-γ水平无关。结论CD4⁺T细胞免疫重建延迟、Th17细胞数明显减少可能与allo-HSCT后IFI的发生有关。

关键词: 异基因造血干细胞移植, 免疫重建, 侵袭性真菌感染, 细胞因子

Abstract:

Objective To investigate the immune reconstitution of CD4⁺T cells after allogeneic hematopoietic stem cell transplantation（allo-HSCT） and its correlation with invasive fungal infection（IFI） in patients with hematological malignancy. Methods A total of 47 patients with hematological malignancy and undergoing allo-HSCT in Binzhou Medical University Hospital from February 2010 to October 2014 were enrolled. A total of 40 healthy subjects were enrolled as control group. After transplantation for 1,2 and 3 months,the count of immune subpopulation and concentration of cytokines were determined by flow cytometry and enzyme-linked immunosorbent assay（ELISA）,respectively. The incidence of IFI after transplantation and its correlation with immune reconstitution of CD4⁺ T cells were observed. Results The counts of CD4⁺ T cells and immune subpopulation increased progressively after transplantation,and the immune subpopulation count after transplantation for 3 months was lower than that in control group. Compared with control group,the levels of interleukin（IL）-6 and IL-10 after transplantation increased,while that of transforming growth factor（TGF）-β decreased. The incidence rate of IFI was 19.15%（9/47）. Multivariate Logistic regression analysis showed that IFI might be related to helper T cell（Th）17 cell count instead of Th1,Th2 and regulatory T cell counts as well as IL-6,IL-10,TGF-β and interferon（IFN）-γ levels. Conclusions After allo-HSCT,the immune reconstitution of CD4⁺T cells delays,and Th17 cell count decreases obviously,which may be related to the occurrence of IFI.

Key words: Allogeneic hematopoietic stem cell transplantation, Immune reconstitution, Invasive fungal infection, Cytokine

中图分类号:

R446.1

彭新国, 孙长华, 安佳佳, 崔艳芳, 董艳, 王健, 高梅兰. 异基因造血干细胞移植后细胞免疫重建与真菌感染的相关性[J]. 检验医学, 2020, 35(5): 447-450.

PENG Xinguo, SUN Changhua, AN Jiajia, CUI Yanfang, DONG Yan, WANG Jian, GAO Meilan. Immune reconstitution after allogeneic hematopoietic stem cell transplantation and its correlation with fungal infection[J]. Laboratory Medicine, 2020, 35(5): 447-450.

图/表 3

参考文献 10

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组别	例数	CD4⁺T细胞	Th17	Th1	Th2	调节性T细胞
移植后1个月组	47	311.136±175.460^*	2.810±1.510^*	51.223±27.201^*	0.671±0.342^*	5.192±2.074^*
移植后2个月组	38	453.290±337.240^*#	3.900±2.052^*	103.450±54.141^*#	2.281±1.982^*#	8.142±3.183^*#
移植后3个月组	41	488.192±211.741^*#	5.186±2.320^*#	120.440±51.369^*#	3.115±2.306^*#	8.920±4.324^*#
对照组	40	976.340±319.623	14.820±6.931	207.141±71.443	5.453±4.263	15.034±6.875

组别	例数	CD4⁺T细胞	Th17	Th1	Th2	调节性T细胞
移植后1个月组	47	311.136±175.460^*	2.810±1.510^*	51.223±27.201^*	0.671±0.342^*	5.192±2.074^*
移植后2个月组	38	453.290±337.240^*#	3.900±2.052^*	103.450±54.141^*#	2.281±1.982^*#	8.142±3.183^*#
移植后3个月组	41	488.192±211.741^*#	5.186±2.320^*#	120.440±51.369^*#	3.115±2.306^*#	8.920±4.324^*#
对照组	40	976.340±319.623	14.820±6.931	207.141±71.443	5.453±4.263	15.034±6.875

组别	例数	IL-6	IL-10	IFN-γ	TGF-β
移植后1个月组	36	5.692±4.713^*	12.593±6.275^*	6.073（0~172.986）	502.636±225.180^*
移植后2个月组	36	19.265±7.325^*#	11.174±4.516^*	4.166（0~53.446）	535.747±241.350^*
移植后3个月组	36	11.536±5.912^*#△	14.666±9.793^*	1.496（0~230.174）	481.957±163.240^*
对照组	40	1.583±0.954	1.344±0.855	3.266（0~131.256）	1509.264±641.060

组别	例数	IL-6	IL-10	IFN-γ	TGF-β
移植后1个月组	36	5.692±4.713^*	12.593±6.275^*	6.073（0~172.986）	502.636±225.180^*
移植后2个月组	36	19.265±7.325^*#	11.174±4.516^*	4.166（0~53.446）	535.747±241.350^*
移植后3个月组	36	11.536±5.912^*#△	14.666±9.793^*	1.496（0~230.174）	481.957±163.240^*
对照组	40	1.583±0.954	1.344±0.855	3.266（0~131.256）	1509.264±641.060

影响因素	回归系数和截距	标准差	χ²值	自由度	P值	回归系数和截距（95%可信区间）
常数项	3.064	0.541	32.111	1	<0.001
Th17	-1.749	-0.780	5.024	1	0.025	0.174（0.051~0.596）
Th1	-0.004	-0.017	0.054	1	0.817	0.996（0.975~1.028）
Th2	-1.988	-1.583	1.578	1	0.209	0.137（0.009~3.001）
调节性T细胞	-0.476	-0.288	2.738	1	0.098	0.621（0.401~0.979）
IL-6	0.000	0.000	0.065	1	0.799	1.000（0.991~1.024）
IL-10	0.024	0.021	1.285	1	0.257	1.024（0.986~1.041）
TGF-β	0.003	0.013	0.057	1	0.812	1.003（0.998~1.006）
IFN-γ	0.017	0.009	3.623	1	0.057	1.017（1.002~1.043）