Circulating cytokine and chemokine patterns associated with cytomegalovirus reactivation after stem cell transplantation

IF 4.6 2区医学 Q2 IMMUNOLOGY

Clinical & Translational Immunology Pub Date : 2023-11-28 DOI:10.1002/cti2.1473

Lauren Stern, Helen M McGuire, Selmir Avdic, Emily Blyth, David Gottlieb, Ellis Patrick, Allison Abendroth, Barry Slobedman

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Abstract

Objectives

Human cytomegalovirus (HCMV) reactivation is the leading viral complication after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Understanding of circulating cytokine/chemokine patterns which accompany HCMV reactivation and correlate with HCMV DNAemia magnitude is limited. We aimed to characterise plasma cytokine/chemokine profiles in 36 allo-HSCT patients (21 with HCMV reactivation and 15 without HCMV reactivation) at four time-points in the first 100-day post-transplant.

Methods

The concentrations of 31 cytokines/chemokines in plasma samples were analysed using a multiplex bead-based immunoassay. Cytokine/chemokine concentrations were compared in patients with high-level HCMV DNAemia, low-level HCMV DNAemia or no HCMV reactivation, and correlated with immune cell frequencies measured using mass cytometry.

Results

Increased plasma levels of T helper 1-type cytokines/chemokines (TNF, IL-18, IP-10, MIG) were detected in patients with HCMV reactivation at the peak of HCMV DNAemia, relative to non-reactivators. Stem cell factor (SCF) levels were significantly higher before the detection of HCMV reactivation in patients who went on to develop high-level HCMV DNAemia (810–52 740 copies/mL) vs. low-level HCMV DNAemia (< 250 copies/mL). High-level HCMV reactivators, but not low-level reactivators, developed an elevated inflammatory cytokine/chemokine profile (MIP-1α, MIP-1β, TNF, LT-α, IL-13, IL-9, SCF, HGF) at the peak of reactivation. Plasma cytokine concentrations displayed unique correlations with circulating immune cell frequencies in patients with HCMV reactivation.

Conclusion

This study identifies distinct circulating cytokine/chemokine signatures associated with the magnitude of HCMV DNAemia and the progression of HCMV reactivation after allo-HSCT, providing important insight into immune recovery patterns associated with HCMV reactivation and viral control.

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干细胞移植后与巨细胞病毒再激活相关的循环细胞因子和趋化因子模式

目的人巨细胞病毒(HCMV)再激活是同种异体造血干细胞移植(allogenetic hematopoietic stem cell transplantation, alloo - hsct)术后最主要的病毒并发症。对伴随HCMV再激活和与HCMV脱氧核糖核酸血症程度相关的循环细胞因子/趋化因子模式的了解有限。我们的目的是在移植后第一个100天的四个时间点对36例同种异体造血干细胞移植患者(21例HCMV再激活，15例未HCMV再激活)的血浆细胞因子/趋化因子谱进行表征。方法采用多重头免疫分析法分析血浆样品中31种细胞因子/趋化因子的浓度。细胞因子/趋化因子浓度在高水平HCMV dna血症、低水平HCMV dna血症或无HCMV再激活患者中进行比较，并与使用细胞计数法测量的免疫细胞频率相关。结果在HCMV DNAemia高峰期，HCMV再激活患者血浆中T辅助1型细胞因子/趋化因子(TNF、IL-18、IP-10、MIG)水平高于非再激活者。干细胞因子(SCF)水平在HCMV再激活检测前显著高于继续发展为高水平HCMV dna血症(810-52 740拷贝/mL)的患者，而低水平HCMV dna血症(< 250拷贝/mL)的患者。高水平的HCMV再激活剂，而非低水平的HCMV再激活剂，在再激活高峰时，炎症细胞因子/趋化因子谱(MIP-1α、MIP-1β、TNF、LT-α、IL-13、IL-9、SCF、HGF)升高。在HCMV再激活患者中，血浆细胞因子浓度与循环免疫细胞频率显示独特的相关性。本研究确定了不同的循环细胞因子/趋化因子特征，这些特征与同种异体造血干细胞移植后HCMV脱氧核糖核酸血症的程度和HCMV再激活的进展有关，为了解与HCMV再激活和病毒控制相关的免疫恢复模式提供了重要的见解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Clinical & Translational Immunology Medicine-Immunology and Allergy

CiteScore

12.00

自引率

1.70%

发文量

审稿时长

13 weeks

期刊介绍： Clinical & Translational Immunology is an open access, fully peer-reviewed journal devoted to publishing cutting-edge advances in biomedical research for scientists and physicians. The Journal covers fields including cancer biology, cardiovascular research, gene therapy, immunology, vaccine development and disease pathogenesis and therapy at the earliest phases of investigation.