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Low Soluble Programmed Cell Death Protein 1 Levels After Allogeneic Stem Cell Transplantation Predict Moderate or Severe Chronic GvHD and Inferior Overall Survival
Frontiers in Immunology ( IF 7.3 ) Pub Date : 2021-09-24 , DOI: 10.3389/fimmu.2021.694843
Lambros Kordelas 1 , Ulrike Buttkereit 1 , Falko M Heinemann 2 , Peter A Horn 2 , Bernd Giebel 2 , Dietrich W Beelen 1 , H Christian Reinhardt 1 , Vera Rebmann 2
Affiliation  

Programmed cell death protein-1 (PD-1) is an inhibitory co-receptor required for regulating immune responsiveness and maintaining immune homeostasis. As PD-1 can be released as bioactive soluble molecule, we investigated the clinical significance of soluble PD-1 (sPD-1) after allogeneic hematopoietic stem cell transplantation (HSCT) regarding graft-versus-host disease (GvHD), relapse, and overall survival (OS) in a mono-centric cohort of 82 patients. Compared to pre-HSCT and to healthy controls, post-HSCT sPD-1 plasma levels were significantly increased during an observation time of three months. Univariate analysis revealed that low sPD-1 plasma levels at month one, two or three post HSCT were associated with acute GvHD grade III-IV, the onset of moderate/severe chronic GvHD (cGvHD) and inferior OS, DFS, and TRM, respectively. No relationship was detected to relapse rates. sPD-1 plasma levels were significantly increased in ATG-treated patients compared to ATG-untreated patients. Multivariate analysis revealed that a low sPD-1 plasma levels status at one or two month(s) after HSCT is an independent indicator for inferior OS, DFS, or TRM. A low sPD-1 plasma levels status at month three post HSCT is predictive for the onset of moderate/severe cGvHD. Thus, our study pinpoints the soluble inhibitory co-receptor PD-1 as a promising candidate molecule for the prediction of clinical HSCT outcome.



中文翻译:

异基因干细胞移植后的低可溶性程序性细胞死亡蛋白 1 水平可预测中度或重度慢性 GvHD 和较差的总体存活率

程序性细胞死亡蛋白-1 (PD-1) 是调节免疫反应和维持免疫稳态所需的抑制性共受体。由于 PD-1 可以作为生物活性可溶性分子释放,我们研究了同种异体造血干细胞移植 (HSCT) 后可溶性 PD-1 (sPD-1) 对移植物抗宿主病 (GvHD)、复发和在 82 名患者的单中心队列中的总生存期 (OS)。与 HSCT 前和健康对照相比,HSCT 后 sPD-1 血浆水平在三个月的观察时间内显着增加。单变量分析显示,HSCT 后第 1、2 或 3 个月的低 sPD-1 血浆水平分别与急性 GvHD III-IV 级、中/重度慢性 GvHD (cGvHD) 的发作以及较差的 OS、DFS 和 TRM 相关. 未检测到与复发率的关系。与未接受 ATG 治疗的患者相比,接受 ATG 治疗的患者的 sPD-1 血浆水平显着升高。多变量分析显示,HSCT 后 1 或 2 个月的低 sPD-1 血浆水平状态是 OS、DFS 或 TRM 较差的独立指标。HSCT 后第三个月的低 sPD-1 血浆水平状态可预测中度/重度 cGvHD 的发作。因此,我们的研究将可溶性抑制性共受体 PD-1 确定为预测临床 HSCT 结果的有希望的候选分子。DFS 或 TRM。HSCT 后第三个月的低 sPD-1 血浆水平状态可预测中度/重度 cGvHD 的发作。因此,我们的研究将可溶性抑制性共受体 PD-1 确定为预测临床 HSCT 结果的有希望的候选分子。DFS 或 TRM。HSCT 后第三个月的低 sPD-1 血浆水平状态可预测中度/重度 cGvHD 的发作。因此,我们的研究将可溶性抑制性共受体 PD-1 确定为预测临床 HSCT 结果的有希望的候选分子。

更新日期:2021-09-24
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