小儿异基因造血干细胞移植后的蛋白质组学筛选显示,γδ T 细胞上抑制性受体 FCRL6 的表达增加与巨细胞病毒再活化有关。

IF 3.2 4区 医学 Q3 CELL BIOLOGY Immunology & Cell Biology Pub Date : 2024-05-10 DOI:10.1111/imcb.12762
Adam Alexandersson, Mikko S Venäläinen, Nelli Heikkilä, Xiaobo Huang, Mervi Taskinen, Pasi Huttunen, Laura L Elo, Minna Koskenvuo, Eliisa Kekäläinen
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引用次数: 0

摘要

我们研究了血液循环中的炎症相关蛋白与小儿异基因造血干细胞移植(HSCT)后并发症之间的关联,以揭示与造血干细胞移植后特定并发症相关的蛋白质组特征或单个可溶性蛋白。在异基因造血干细胞移植后两年的随访期间,我们使用一种名为 "接近延伸测定"(Proximity Extension Assay)的蛋白质组学方法,对27名儿童(1-18岁)的180种不同蛋白质以及临床变量、细胞免疫重建和血液病毒拷贝数进行了反复测定。使用无监督分层聚类和基于回归的方法对蛋白质概况进行了分析,同时使用经 Bonferroni 校正的 Mann-Whitney U 检验来比较单个蛋白质与结果的时间点特异性。异基因造血干细胞移植后6个月时,我们可以发现蛋白质特征模式与慢性移植物抗宿主病、病毒感染、复发和死亡等并发症的发生有关。在对蛋白质标记物进行单独分析时,有巨细胞病毒(CMV)病毒血症的患者血浆中抑制性和细胞毒性T细胞表面蛋白FCRL6(Fc受体样6)的浓度较高[在6、12和24个月的时间点,其对数倍变化分别为1.5(P = 0.00099)、2.5(P = 0.00035)和2.2(P = 0.045)]。流式细胞术证实,先天性γδT细胞中的FCRL6表达较高,表明这些细胞参与控制造血干细胞移植受者的CMV再激活。总之,细胞毒性 T 细胞上潜在的可药用 FCRL6 受体似乎在造血干细胞移植后控制 CMV 病毒血症中发挥作用。此外,我们的研究结果表明,系统级分析是对异基因造血干细胞移植中单一生物标志物研究的有益补充。
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Proteomics screening after pediatric allogenic hematopoietic stem cell transplantation reveals an association between increased expression of inhibitory receptor FCRL6 on γδ T cells and cytomegalovirus reactivation

We studied the associations between inflammation-related proteins in circulation and complications after pediatric allogenic hematopoietic stem cell transplantation (HSCT), to reveal proteomic signatures or individual soluble proteins associated with specific complications after HSCT. We used a proteomics method called Proximity Extension Assay to repeatedly measure 180 different proteins together with clinical variables, cellular immune reconstitution and blood viral copy numbers in 27 children (1–18 years of age) during a 2-year follow-up after allogenic HSCT. Protein profile analysis was performed using unsupervised hierarchical clustering and a regression-based method, while the Bonferroni-corrected Mann–Whitney U-test was used for time point–specific comparison of individual proteins against outcome. At 6 months after allogenic HSCT, we could identify a protein profile pattern associated with occurrence of the complications such as chronic graft-versus-host disease, viral infections, relapse and death. When protein markers were analyzed separately, the plasma concentration of the inhibitory and cytotoxic T-cell surface protein FCRL6 (Fc receptor-like 6) was higher in patients with cytomegalovirus (CMV) viremia [log2-fold change 1.5 (P = 0.00099), 2.5 (P = 0.00035) and 2.2 (P = 0.045) at time points 6, 12 and 24 months]. Flow cytometry confirmed that FCRL6 expression was higher in innate-like γδ T cells, indicating that these cells are involved in controlling CMV reactivation in HSCT recipients. In conclusion, the potentially druggable FCRL6 receptor on cytotoxic T cells appears to have a role in controlling CMV viremia after HSCT. Furthermore, our results suggest that system-level analysis is a useful addition to the studying of single biomarkers in allogenic HSCT.

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来源期刊
Immunology & Cell Biology
Immunology & Cell Biology 医学-免疫学
CiteScore
7.50
自引率
2.50%
发文量
98
审稿时长
4-8 weeks
期刊介绍: The Australasian Society for Immunology Incorporated (ASI) was created by the amalgamation in 1991 of the Australian Society for Immunology, formed in 1970, and the New Zealand Society for Immunology, formed in 1975. The aim of the Society is to encourage and support the discipline of immunology in the Australasian region. It is a broadly based Society, embracing clinical and experimental, cellular and molecular immunology in humans and animals. The Society provides a network for the exchange of information and for collaboration within Australia, New Zealand and overseas. ASI members have been prominent in advancing biological and medical research worldwide. We seek to encourage the study of immunology in Australia and New Zealand and are active in introducing young scientists to the discipline.
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