CTLA-4与CD28在FⅧ抑制物阳性的血友病A患儿中的表达分析

doi:10.3969/j.issn.1006-7795.2018.03.001

首都医科大学学报 ›› 2018, Vol. 39 ›› Issue (3): 309-313.doi: 10.3969/j.issn.1006-7795.2018.03.001

• 血液病学基础与临床研究 • 上一篇下一篇

CTLA-4与CD28在FⅧ抑制物阳性的血友病A患儿中的表达分析

李杨, 陈振萍, 李刚, 甄英姿, 吴心怡, 吴润晖

首都医科大学附属北京儿童医院血液肿瘤中心, 北京 100045

收稿日期:2018-04-19 出版日期:2018-05-21 发布日期:2018-06-11
通讯作者: 吴润晖 E-mail:runhuiwu@hotmail.com
基金资助:
北京市自然科学基金（7162059），首都卫生发展科研专项（首发-2014-2-2092），北京市医院管理局临床医学发展专项（ZY201404），诺和诺德基金项目。

Expression of CTLA-4 and CD28 in hemophilia A children with FⅧ inhibitor

Li Yang, Chen Zhenping, Li Gang, Zhen Yingzi, Wu Xinyi, Wu Runhui

Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, Beijing 100045, China

Received:2018-04-19 Online:2018-05-21 Published:2018-06-11
Supported by:
This study was supported by Natural Science Foundation of Beijing (7162059), Capital Health Research and Development of Special (2014-2-2092),Beijing Municipal Administration of Hospital Clinical Medicine Development(ZY201404), the NOVO Nordisk Funding Project.

摘要/Abstract

摘要： 目的探讨细胞毒T淋巴细胞相关抗原4（cytotoxic T lymphocyte-associated antigen-4，CTLA-4）与CD28在FⅧ抑制物阳性的血友病A患儿中表达百分比。方法收集自2016年12月1日至2018年1月1日就诊于首都医科大学附属北京儿童医院血友病专业门诊的血友病A患儿，共计入组患儿58例，其中FⅧ抑制物阳性者28例，阴性者30例。应用改良Nijmegen法检测FⅧ抑制物滴度，流式细胞术检测外周血T细胞上的CD3、CD4、CTLA-4和CD28的表达，分析比较两组CTLA-4+Th细胞、CD28+Th细胞的百分比和CTLA-4/CD28轴的平衡情况。结果 FⅧ抑制物阳性组患儿外周血CTLA-4+Th细胞百分比为2.95%（1.41%，5.50%），阴性组患儿表达百分比为4.95%（2.20%，7.80%），阳性组显著低于阴性组（P=0.038）；阳性组患儿外周血CTLA-4/CD28细胞比值为0.03（0.01，0.06），阴性组患儿表达比值为0.05（0.02，0.08），阳性组显著低于阴性组（P=0.042）；而CD28+Th细胞表达差异无统计学意义（P=0.065）。对低滴度组和高滴度组进行比较，上述检测细胞在两组间差异无统计学意义。结论 CTLA-4/CD28细胞百分比比值在FⅧ抑制物阳性与阴性的血友病A患儿存在差异，抑制物阳性组显著低于阴性组，并且这种差异主要由CTLA-4+Th细胞表达百分比差异引起。CTLA-4的低表达可能是抑制物产生的原因之一。

关键词: CTLA-4/CD28, 血友病A, 抑制物

Abstract: Objective To explore the expression of cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and CD28 in children with hemophilia A inhibitor.Methods Data of a total of 58 children with hemophilia A (FⅧ:C ≤ 2%) in the Beijing Children's Hospital, Capital Medical University from December 1, 2016 to January 1, 2018 were collected, 28 cases were positive for the inhibitor and 30 cases were negative.Improved Nijmegen assay was used to test inhibitor titer and flow cytometry to test percentage of CD3、CD4、CTLA-4 and CD28 on T cells in peripheral blood. We analyzed the expression of CTLA-4/CD28 axis and CTLA-4+ Th cells, CD28+ Th cells of children with hemophilia A inhibitor positive and negative, and to determine the difference.Results The proportion of CTLA-4+Th cells in peripheral blood of children with FⅧ inhibitor was 2.95%(1.41%,5.50%), and negative group was 4.95%(2.20%,7.70%). The positive group was significantly lower than that of negative group (P=0.038). The expression of CD28+Th cells was not different. The CTLA-4/CD28 cell in peripheral blood of the positive group was 0.03 (0.01,0.06), and the negative group was 0.05 (0.02,0.08). the positive group was significantly lower than that of the negative group (P=0.042). There was no significant difference between the two groups in low titer group and high titer group.Conclusion The results of this study showed that expression of CTLA-4+T cells in peripheral blood of children with hemophilia A inhibitor positive was significantly lower than that in the negative children. We infer that the imbalance of CTLA-4/CD28 axis results in the development of inhibitor, while the insufficient expression of CTLA-4 is the main factor. Insufficient expression of CTLA-4 may be one of the important immunosuppressive effects of inhibitors generation.

Key words: CTLA-4/CD28, hemophilia A, inhibitor

中图分类号:

R725.5

李杨, 陈振萍, 李刚, 甄英姿, 吴心怡, 吴润晖. CTLA-4与CD28在FⅧ抑制物阳性的血友病A患儿中的表达分析[J]. 首都医科大学学报, 2018, 39(3): 309-313.

Li Yang, Chen Zhenping, Li Gang, Zhen Yingzi, Wu Xinyi, Wu Runhui. Expression of CTLA-4 and CD28 in hemophilia A children with FⅧ inhibitor[J]. Journal of Capital Medical University, 2018, 39(3): 309-313.

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CTLA-4与CD28在FⅧ抑制物阳性的血友病A患儿中的表达分析

Expression of CTLA-4 and CD28 in hemophilia A children with FⅧ inhibitor

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