Prognostic Biomarkers for Thrombotic Microangiopathy after Acute Graft-versus-Host Disease: A Nested Case-Control Study
Prognostic Biomarkers for Thrombotic Microangiopathy after Acute Graft-versus-Host Disease: A Nested Case-Control Study
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DOI：
10.1016/j.jtct.2020.12.010
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发表时间：
2021-04-07
影响因子：
3.2
通讯作者：
Hingorani, Sangeeta R.
中科院分区：
文献类型：
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作者：
Li, Ang;Bhatraju, Pavan K.;Hingorani, Sangeeta R.
移植相关血栓性微血管病（Transplantation-associated thrombotic microangiopathy，TA-TMA）是异基因造血细胞移植（allogeneic hematopoietic cell transplantation，HCT）的一种并发症，常发生在急性移植物抗宿主病（acute graft-versus-host disease，aGVHD）后。在这项研究中，我们的目的是确定早期TMA生物标志物与aGVHD患者。我们进行了一项巢式病例对照研究，从一个前瞻性队列的异基因HCT受体，匹配的时间和严重程度的前期aGVHD。我们从队列中的208例患者中确定了13例TMA病例和25例非TMA对照。使用多变量条件Logistic回归，TMA与非TMA相比的优势比为2.65（95%置信区间[CI]，1.00 - 7.04），终末补体复合物sC 5 b 9每增加100 ng/mL，2.62在aGVHD发作时，血管生成素-2（ANG 2）每增加1000 pg/mL（95% CI，1.56至4.38）。ADAMTS 13和血管性血友病因子（VWF）抗原与TMA无关。使用考克斯回归模型，在aGVHD发作时纳入sC 5 b 9>300 ng/mL和ANG 2>3000 pg/mL，校正的死亡率风险比为5.33（95% CI，1.57 - 18.03）（均升高）和4.40（95% CI，1.60至12.07）的中危组（一个升高）相比，低危组（均未升高）。总之，我们发现aGVHD发作时升高的sC 5 b 9和ANG 2水平与TMA的发展相关，并且在考虑aGVHD的时间和严重程度后可能与死亡率相关。结果提示补体激活和内皮功能障碍在TMA的发病机制中起重要作用。在aGVHD发病时测量这些生物标志物可能为预防性试验提供预后信息，并改善临床护理。(C)2020年美国移植和细胞治疗学会。爱思唯尔公司出版All rights reserved.
Transplantation-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic hematopoietic cell transplantation (HCT) that often occurs following the development of acute graft-versus-host disease (aGVHD). In this study, we aimed to identify early TMA biomarkers among patients with aGVHD. We performed a nested-case-control study from a prospective cohort of allogeneic HCT recipients, matching on the timing and severity of antecedent aGVHD. We identified 13 TMA cases and 25 non-TMA controls from 208 patients in the cohort. Using multivariable conditional logistic regression, the odds ratio for TMA compared with non-TMA was 2.65 (95% confidence interval [CI], 1.00 to 7.04) for every 100 ng/mL increase in terminal complement complex sC5b9 and 2.62 (95% CI, 1.56 to 4.38) for every 1000 pg/mL increase in angiopoietin-2 (ANG2) at the onset of aGVHD. ADAMTS13 and von Willebrand factor (VWF) antigens were not appreciably associated with TMA. Using a Cox regression model incorporating sC5b9 >300 ng/mL and ANG2 >3000 pg/mL at the onset of aGVHD, the adjusted hazard ratio for mortality was 5.33 (95% CI, 1.57 to 18.03) for the high-risk group (both elevated) and 4.40 (95% CI, 1.60 to 12.07) for the intermediate-risk group (one elevated) compared with the low-risk group (neither elevated). In conclusion, we found that elevated sC5b9 and ANG2 levels at the onset of aGVHD were associated with the development of TMA and possibly mortality after accounting for the timing and severity of aGVHD. The results suggest important roles of complement activation and endothelial dysfunction in the pathogenesis of TMA. Measurement of these biomarkers at the onset of aGVHD may informprognostic enrichment for preventive trials and improve clinical care. (C) 2020 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.