The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT.
The level of Tim-3+CD8+ T cells can serve as a potential marker for evaluating the severity of acute graft-versus-host disease after haplo-PBSCT.
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DOI：
10.1590/1414-431x2023e12997
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发表时间：
2023
影响因子：
2.3
通讯作者：
Jiang, Ming
中科院分区：
文献类型：
--
作者：
Pang, Nannan;Yu, Mingkai;Xu, Jianli;Yuan, Hailong;Chen, Gang;Wang, Dong;Han, Chunxia;Wang, Weiguo;Ding, Jianbing;Jiang, Ming
早期准确诊断异基因造血干细胞移植后急性移植物抗宿主病（aGVHD）对于患者的预后至关重要。本研究确定了人类白细胞抗原（HLA）-半相合外周血造血干细胞移植（haplo-PBSCT）后aGVHD严重程度的潜在生物标志物。我们纳入了20名健康受试者和57名接受haplo-PBSCT的患者。在这些患者中，22例在haplo-PBSCT后发生aGVHD。结果显示，aGVHD患者具有显著增加的Tim-3+/穿孔蛋白+/粒酶B+ CD 8 + T细胞水平，但显著降低的半乳糖凝集素-9。I-II级aGVHD和III-IV级aGVHD之间的半乳糖凝集素-9和Tim-3+/颗粒酶B+ CD 8 + T细胞的差异也是显著的。在体外，aGVHD患者的CD 8 + T细胞凋亡在Tim-3/Galectin-9途径激活后显著增加，从而减少颗粒酶B的分泌。单因素分析显示，Tim-3+ CD 8 + T细胞水平是严重aGVHD的危险因素。ROC曲线分析显示，高水平的Tim-3+ CD 8 + T细胞对重度aGVHD具有显著的诊断价值，曲线下面积为0.854，临界值为14.155%。结论：Tim-3与外源性Galectin-9的结合可促进CD 8 + T细胞凋亡，并影响颗粒酶B的分泌。Tim-3+ CD 8 + T细胞有可能作为免疫学标记物，用于评估haplo-PBSCT后aGVHD的严重程度，并识别严重aGVHD风险较高的患者。
Early and accurate diagnosis of acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation is crucial for the prognosis of patients. This study identified a potential biomarker for the severity of aGVHD after human leukocyte antigen (HLA)-haploidentical peripheral blood hematopoietic stem cell transplantation (haplo-PBSCT). We included 20 healthy subjects and 57 patients who underwent haplo-PBSCT. Of these patients, 22 developed aGVHD after haplo-PBSCT. The results showed that patients with aGVHD had significantly increased levels of Tim-3+/Perforin+/Granzyme B+CD8+ T cells, but significantly decreased Galectin-9. The differences in Galectin-9 and Tim-3+/Granzyme B+CD8+ T cells between grade I-II aGVHD and III-IV aGVHD were also significant. In vitro, the apoptosis of CD8+ T cells from aGVHD patients was significantly increased after Tim-3/Galectin-9 pathway activation, which decreased Granzyme B secretion. As revealed by univariate analysis, the level of Tim-3+CD8+ T cells was a risk factor for severe aGVHD. ROC analysis demonstrated that high levels of Tim-3+CD8+ T cells had a significant diagnostic value for severe aGVHD, with an area under the curve of 0.854 and cut-off value of 14.155%. In conclusion, the binding of Tim-3 with exogenous Galectin-9 can promote apoptosis of CD8+ T cells and affect the secretion of Granzyme B. Tim-3+CD8+ T cells have the potential to serve as immunological markers for assessing the severity of aGVHD after haplo-PBSCT and identifying patients at a higher risk for severe aGVHD.