Global Metabolomics in Allogeneic Hematopoietic Cell Transplantation Recipients Discordant for Chronic Graft-versus-Host Disease

IF 4.3 Q1 Medicine
Debra Lynch Kelly , Nosha Farhadfar , Angela Starkweather , Timothy J Garrett , Yingwei Yao , John R. Wingard , Iqbal Mahmud , Victoria Menzies , Param Patel , Karima M. Alabasi , Debra Lyon
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引用次数: 7

Abstract

Chronic graft-versus-host disease (cGVHD) remains a significant late effect issue for allogeneic hematopoietic cell transplantation (allo-HCT) survivors, contributing to morbidity and mortality. The etiology of cGVHD is not well elucidated. Owing to a lack of early diagnostic tests and pathophysiology ambiguity, targeted treatments remain limited. Biomarkers for prediction, control response, or prognostication have not yet been identified. Metabolomics, the quantification of metabolites, is a potential biomarker of cGVHD but has not been evaluated in this population. In this study, we examined global metabolites of stored plasma to identify differentially expressed metabolites of individuals discordant for cGVHD following allo-HCT. A descriptive, comparative, cross-sectional study design was used to examine differentially expressed metabolites of plasma samples obtained from 40 adult allo-HCT recipients (20 with cGVHD and 20 without cGVHD) from 2 parent studies. Metabolomics profiling was conducted at the University of Florida's Southeast Center for Integrative Metabolomics. Full experimental methods followed a previously published method. All statistical analyses were performed by a PhD-prepared, trained bioinformatics statistician. There were 10 differentially expressed metabolites between participants with cGVHD and those without cGVHD. Differential metabolites included those related to energy metabolism (n = 3), amino acid metabolism (n = 3), lipid metabolism (n = 2), caffeine metabolism (n = 1), and neurotransmission (n = 1). Serotonin had the greatest fold change (21.01). This study suggests that cGVHD may be associated with expanded cellular energy and potentially mitochondrial dysfunction. The differential metabolic profile between patients with and without cGVHD indicates metabolic perturbations that merit further exploration as potential biomarkers of cGVHD. These findings support the need for further examination using a larger, prospective study design to identify metabolomic risk factors that may signal the need for earlier preventive measures and earlier treatment to reduce cGVHD.

慢性移植物抗宿主病的异基因造血细胞移植受体的整体代谢组学不一致
慢性移植物抗宿主病(cGVHD)仍然是异基因造血细胞移植(同种异体造血细胞移植)幸存者的一个重要的晚期效应问题,导致发病率和死亡率。cGVHD的病因尚不清楚。由于缺乏早期诊断测试和病理生理学的模糊性,有针对性的治疗仍然有限。预测、控制反应或预测的生物标志物尚未确定。代谢组学,即代谢物的量化,是cGVHD的潜在生物标志物,但尚未在该人群中进行评估。在这项研究中,我们检测了储存血浆的整体代谢物,以鉴定同种异体hct后cGVHD不一致个体的差异表达代谢物。采用描述性、对比性、横断面研究设计,对来自两项亲本研究的40名成人同种异体hct受体(20名cGVHD患者和20名非cGVHD患者)血浆样本中代谢物的差异表达进行了检测。代谢组学分析在佛罗里达大学东南综合代谢组学中心进行。完整的实验方法遵循先前发表的方法。所有统计分析均由博士学位准备,训练有素的生物信息学统计学家进行。在cGVHD患者和非cGVHD患者之间有10种代谢物表达差异。差异代谢物包括与能量代谢(n = 3)、氨基酸代谢(n = 3)、脂质代谢(n = 2)、咖啡因代谢(n = 1)和神经传递(n = 1)相关的代谢物,其中血清素的倍数变化最大(21.01)。这项研究表明,cGVHD可能与细胞能量扩大和潜在的线粒体功能障碍有关。cGVHD患者和非cGVHD患者之间的代谢谱差异表明,代谢扰动值得进一步探索,作为cGVHD的潜在生物标志物。这些发现支持了进一步研究的需要,通过更大的前瞻性研究设计来确定代谢组学危险因素,这些因素可能表明需要早期预防措施和早期治疗来降低cGVHD。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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