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慢性移植物抗宿主病患者免疫细胞亚群分选的表面标志组合策略
A combined strategy of surface markers for sorting immune cell subsets in patients with chronic graft-versus-host disease
- 第三军医大学学报 2021年43卷第21期 页码：2331-2336
- 作者机构：
1.563099 贵州 遵义，遵义医科大学第二附属医院检验科
2.400037 重庆，陆军军医大学(第三军医大学)第二附属医院血液病医学中心，全军血液病中心，创伤、烧伤与复合伤国家重点实验室
- 作者简介：
[葛晓军，E-mail: gxj_199421@163.com GE Xiaojun, E-mail: gxj_199421@163.com
[杨世杰，E-mail: xyzysj102@163.com YANG Shijie, E-mail: xyzysj102@163.com
- 基金信息：国家自然科学基金面上项目(81873424);重庆市科技创新领军人才(CSTCCXLJRC201718);重庆市科卫联合医学科研项目(2021MSXM140);作者贡献声明 本文由杜雨軒、王平参与本研究的研究方案设计、样本收集、数据处理、文章撰写及修改，作者张曦、王筱淇、黄瑞昊参与本文的数据处理及修改，洪涛、王蔚浩、何云地、邓小娟、刘帅妹参与本文的修改，共同通信作者葛晓军、杨世杰参与本研究的研究方案设计及文章修改
DOI：10.16016/j.1000-5404.202108057
中图分类号： R392.8;R617;R733.7收稿：2021-08-10，
修回：2021-09-20，
纸质出版：2021-11-15
- 稿件说明：
移动端阅览
杜雨軒, 王平, 葛晓军, 等. 慢性移植物抗宿主病患者免疫细胞亚群分选的表面标志组合策略[J]. 第三军医大学学报, 2021,43(21):2331-2336.
Yuxuan DU, Ping WANG, Xiaojun GE, et al. A combined strategy of surface markers for sorting immune cell subsets in patients with chronic graft-versus-host disease[J]. Journal of Third Military Medical University, 2021, 43(21): 2331-2336.
杜雨軒, 王平, 葛晓军, 等. 慢性移植物抗宿主病患者免疫细胞亚群分选的表面标志组合策略[J]. 第三军医大学学报, 2021,43(21):2331-2336. DOI： 10.16016/j.1000-5404.202108057.
Yuxuan DU, Ping WANG, Xiaojun GE, et al. A combined strategy of surface markers for sorting immune cell subsets in patients with chronic graft-versus-host disease[J]. Journal of Third Military Medical University, 2021, 43(21): 2331-2336. DOI： 10.16016/j.1000-5404.202108057.
摘要
目的
2
观测慢性移植物抗宿主病(chronic graft-versus-host disease
cGVHD)患者免疫细胞亚群分布变化规律，探讨免疫细胞表面标志物分选出的特定细胞亚群在cGVHD发病过程中对疾病发展的预测作用。
方法
2
收集2020年10月至2021年7月在陆军军医大学第二附属医院血液病医学中心接受造血干细胞移植后的患者58例，根据移植后是否发生cGVHD分为cGVHD组(发生cGVHD，
n
=43)和对照组(未发生cGVHD，
n
=15)，采用流式细胞术分析两组患者免疫细胞亚群比率及分布情况，募集患者原发诊断包括ALL、AML、CML、MDS、SAA和重型β地中海贫血。其中发生cGVHD的中位时间为178.5(47~1 328)d，每例患者于随访过程中发生cGVHD时或病程中随访当日留取外周血标本。
结果
2
cGVHD组患者外周血中调节性T细胞(regulatory T cells，Tregs)及过渡型B细胞的分布水平显著降低，CD19
+
B淋巴细胞的分布水平较对照组显著增加；接受造血干细胞移植后发生cGVHD的患者组外周血中Tregs较接受造血干细胞移植后未发生cGVHD的患者组明显降低，中度cGVHD患者Th17细胞较轻度患者分布水平显著升高，CD19
+
B淋巴细胞在轻度、中度患者中显著升高；比较不同cGVHD靶器官，仅累及皮肤病变的患者与仅累及肝脏的患者Tregs较对照组中显著降低，而合并皮肤及肝脏损伤患者的外周血中滤泡辅助T细胞的分布显著高于仅累及黏膜或眼睛等器官的患者。
结论
2
移植后免疫细胞亚群检测是临床辅助cGVHD诊疗随访的重要参考指标。使用免疫细胞表面标志组合的特异性策略分选出的调节性T细胞、过渡型B细胞对cGVHD患者的发病及严重程度、靶器官损伤都有特异性的指示作用。
Abstract
Objective
2
To explore the distribution of immune cell subsets in patients with chronic graft-versus-host disease (cGVHD) and investigate the predictive values of specific cell subsets sorted by surface markers in the development of cGVHD.
Methods
2
From October 2020 to July 2021
58 patients who received he
matopoietic stem cell transplantation (HSCT) from the Hematology Medical Center of the Second Affiliated Hospital of the Army Medical University were collected in this study. Flow cytometry was used to detect the ratio of immune cell subpopulations in the cGVHD patients (cGVHD group
n
=43) and those without (control group
n
=15) who received allogeneic HSCT during the same period. Primary diagnoses of the recruited patients included acute lymphoblastic leukemia (ALL)
acute myeloid leukemia (AML)
chronic myeloid leukemia (CML)
myelodysplastic syndromes (MDS)
severe aplastic anemia (SAA)
and β-thalassemia major. The median time to occurrence of cGVHD was 178.5 (47~1 328) d. Peripheral blood (PB) samples were collected for each patient when cGVHD occurred during follow-up or on the day of follow-up during the course of the disease.
Results
2
The percentages of PB regulatory T cells (Tregs) and transitional B cells were significantly reduced in the cGVHD group (
P
<
0.05)
and that of CD19
+
B lymphocytes was higher than the control group. The percentage of Tregs differed from the cGVHD patients with different severities (
P
<
0.05). The percentage of Th17-like cells in the patients with moderate cGVHD was significantly higher than patients with mild cGVHD. CD19
+
B lymphocytes showed higher percentage in the patients with mild and moderate cGVHD. In the comparison among different targeted organs of cGVHD
only the Tregs percentage was significantly lower in the patients with skin and liver damage than control group
while the percentage of follicular helper T cells in the patients with skin and liver damage was significantly higher than those only having mucous membrane or eye organ involvement.
Conclusion
2
Distribution of immune cell subsets after HSCT is an important reference marker for the diagnosis
treatment and prognosis of cGVHD. Treg cells and transitional B cells which are sorted with a special combined strategy of surface markers play specific guiding roles in the pathogenesis
severity and damage of targeted organs of cGVHD.
关键词
Keywords
references
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