A systematic review of diagnostic, prognostic, and risk blood and urine biomarkers of transplant-associated thrombotic microangiopathy.
A systematic review of diagnostic, prognostic, and risk blood and urine biomarkers of transplant-associated thrombotic microangiopathy.
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DOI：
10.3389/fimmu.2022.1064203
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发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
移植相关血栓性微血管病（TA-TMA）是异基因和自体造血细胞治疗（HCT）的一种日益被认识到的并发症，与显著的发病率和死亡率相关。虽然该疾病的中心驱动因素被认为是内皮损伤和补体激活，但尚未鉴定出特异性诊断生物标志物。TA-TMA通常使用由非特异性临床和实验室特征组成的标准进行诊断。一些患者会有一个自我缓解的过程，但超过一半的发展多器官功能障碍或死亡，使预后生物标志物至关重要。TA-TMA的预防是其他HCT并发症（如移植物抗宿主病）的核心方法，但在很大程度上尚未经过测试，部分原因是缺乏识别的早期高风险生物标志物。我们进行了一项系统回顾，总结了TA-TMA的诊断、早期风险和预后生物标志物。我们筛选了1524篇引文的标题和摘要。在筛选出重复后，我们阅读了979篇论文的摘要，并全面审查了132篇全文出版物。31篇文献符合5例以上TA-TMA患者的入选标准，并报告了与诊断、预后或疾病后期发展风险相关的指标。14项研究（45%）是针对成人的，12项（39%）是针对18岁以下的儿童的，3项包括儿童和成人，2项没有报告年龄。有53个生物标志物或生物标志物签名条目，总共有27个独特的生物标志物。只有四种生物标志物报告了敏感性和特异性。具有最稳健数据的单一生物标志物是sC 5 b-9，其具有诊断、预后和风险意义。生物标志物组合的研究很少。由于研究之间存在显著异质性，因此未进行荟萃分析。研究的局限性包括样本量小，研究设计具有高偏倚风险（即，病例-对照）、样品收集的时间和对照的选择。此外，只有两项（6%）研究包括培训和验证队列。由于大多数生物标志物没有正常值，或者在HCT设置中不能假设正常值，因此需要临界点来分层组。在未来，需要多机构的合作努力，对连续招募的患者进行严格设计的前瞻性研究，在TA-TMA诊断时收集样本，仔细选择对照，并在单独的队列中验证选定的生物标志物和截止点。
Transplant-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of allogeneic and autologous hematopoietic cellular therapy (HCT), associated with significant morbidity and mortality. Although the central drivers of the disease are thought to be endothelial damage and complement activation, no specific diagnostic biomarkers have been identified. TA-TMA is typically diagnosed using criteria comprised of non-specific clinical and laboratory features. Some patients will have a self-remitting course, but more than half develop multi-organ dysfunction or die, making prognostic biomarkers critical. Prevention of TA-TMA, an approach central to other HCT complications such as graft-versus-host disease, is largely untested in part due to a lack of identified early high-risk biomarkers. We conducted a systematic review to summarize the diagnostic, early risk, and prognostic biomarkers of TA-TMA. We screened the titles and abstracts of 1524 citations. After screening out duplications, we read the abstracts of 979 papers and fully reviewed 132 full-text publications. Thirty-one publications fulfilled the inclusion criteria of more than five patients with TA-TMA and a reported measure of association with diagnosis, prognosis, or risk of later development of the disease. Fourteen studies (45%) were with adults, 12 (39%) were with children <18 years old, three included both children and adults, and two did not report age. There were 53 biomarker or biomarker signature entries, and a total of 27 unique biomarkers. Only four biomarkers reported sensitivity and specificity. The single biomarker with the most robust data was sC5b-9, which conferred diagnostic, prognostic, and risk implications. Studies of combinations of biomarkers were rare. No meta-analyses were performed because of significant heterogeneity between studies. The limitations of studies included small sample size, study designs with a high risk of bias (i.e., case–control), the timing of sample collection, and the selection of controls. Furthermore, only two (6%) studies included a training and validation cohort. Cut-off points are needed to stratify groups, as most biomarkers do not have normal values, or normal values cannot be assumed in the HCT setting. In the future, multi-institutional, collaborative efforts are needed to perform rigorously designed, prospective studies with serially enrolled patients, with samples collected at the time of TA-TMA diagnosis, careful selection of controls, and validation of selected biomarkers and cut-off points in a separate cohort.
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影响因子：
3.2
作者：
Li, Ang;Bhatraju, Pavan K.;Hingorani, Sangeeta R.
通讯作者：
Hingorani, Sangeeta R.
DOI：
10.1016/j.bbmt.2015.07.004
发表时间：
2015-10
期刊：
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
影响因子：
--
作者：
Akil A;Zhang Q;Mumaw CL;Raiker N;Yu J;Velez de Mendizabal N;Haneline LS;Robertson KA;Skiles J;Diaz-Ricart M;Carreras E;Renbarger J;Hanash S;Bies RR;Paczesny S
通讯作者：
Paczesny S
影响因子：
7.5
作者：
Elfeky, Reem;Lucchini, Giovanna;Veys, Paul
通讯作者：
Veys, Paul
影响因子：
20.3
作者：
Jodele, Sonata;Dandoy, Christopher E.;Davies, Stella M.
通讯作者：
Davies, Stella M.
影响因子：
20.3
作者：
Jodele, Sonata;Davies, Stella M.;Laskin, Benjamin L.
通讯作者：
Laskin, Benjamin L.