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危险相关分子模式对急性移植物抗宿主病生存的影响。

The effect of danger-associated molecular patterns on survival in acute graft versus host disease.

作者信息

Çelik Serhat, Kaynar Leylagül, Güven Zeynep Tuğba, Atasever Duran Kübra, Kontaş Olgun, Keklik Muzaffer, Ünal Ali

机构信息

Department of Hematology, Faculty of Medicine, Kırıkkale University, Kırıkkale, Türkiye.

Department of Hematology, Faculty of Medicine, Medipol Mega University, İstanbul, Türkiye.

出版信息

Bone Marrow Transplant. 2024 Feb;59(2):189-195. doi: 10.1038/s41409-023-02145-7. Epub 2023 Nov 7.

DOI:10.1038/s41409-023-02145-7
PMID:37935781
Abstract

Danger-associated molecular patterns (DAMPs) are molecules that can initiate and maintain robust inflammatory responses and were investigated in the pathogenesis of graft versus host disease (GvHD). Uric acid (UA) and fibrinogen (Fib) are DAMPs released from damaged tissue during allogeneic hematopoietic stem cell transplantation (allo-HCT) and GvHD. We aimed to evaluate the effects of UA and Fib levels on survival in GvHD. One hundred seventy-four patients with grade 2-4 acute GvHD were included. UA and Fib levels were evaluated on allo-HCT day 0 and GvHD on days 0, 7, 14, and 28. Fib GvHD day 0 was the independent predictor for overall survival (OS), non-relapse mortality (NRM), and progression-free survival in multivariable models (HR 0.98, p < 0.001; HR 0.98, p = 0.001, HR 0.98, p = 0.006, respectively). Also UA GvHD day 28 was the independent predictor for OS and NRM (HR 0.77, p = 0.004; HR 0.76, p = 0.011, respectively). Our results indicated that hypouricemia and hypofibrinogenemia were associated with a significantly shorter OS and higher NRM. UA and Fib are remarkable molecules in GvHD because they are routinely utilized, readily available, can be therapeutic targets, and have DAMPs and antioxidant features.

摘要

危险相关分子模式(DAMPs)是能够引发并维持强烈炎症反应的分子,本研究对其在移植物抗宿主病(GvHD)发病机制中的作用进行了探究。尿酸(UA)和纤维蛋白原(Fib)是异基因造血干细胞移植(allo-HCT)和GvHD过程中受损组织释放的DAMPs。我们旨在评估UA和Fib水平对GvHD患者生存的影响。研究纳入了174例2-4级急性GvHD患者。在allo-HCT第0天评估UA和Fib水平,并在第0、7、14和28天评估GvHD情况。在多变量模型中,Fib第0天的GvHD是总生存期(OS)、非复发死亡率(NRM)和无进展生存期的独立预测因素(HR 0.98,p < 0.001;HR 0.98,p = 0.001;HR 0.98,p = 0.006)。此外,UA第28天的GvHD是OS和NRM的独立预测因素(HR 0.77,p = 0.004;HR 0.76,p = 0.011)。我们的结果表明,低尿酸血症和低纤维蛋白原血症与显著缩短的OS和更高的NRM相关。UA和Fib在GvHD中是重要分子,因为它们是常规使用的、易于获得的、可作为治疗靶点,并且具有DAMPs和抗氧化特性。

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本文引用的文献

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The role of serum uric acid in the prediction of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation.血清尿酸在异基因造血干细胞移植中预测移植物抗宿主病的作用。
J Clin Lab Anal. 2020 Jul;34(7):e23271. doi: 10.1002/jcla.23271. Epub 2020 Mar 2.
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The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease.
移植后并发症:分子机制与治疗干预
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