Nannan Pang, Mingkai Yu, Jianli Xu, Hailong Yuan, Gang Chen, Dong Wang, Chunxia Han, Weiguo Wang, Jianbing Ding, Ming Jiang
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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.</p>","PeriodicalId":9088,"journal":{"name":"Brazilian Journal of Medical and Biological Research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10729645/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Nannan Pang, Mingkai Yu, Jianli Xu, Hailong Yuan, Gang Chen, Dong Wang, Chunxia Han, Weiguo Wang, Jianbing Ding, Ming Jiang\",\"doi\":\"10.1590/1414-431X2023e12997\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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. 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引用次数: 0
摘要
异基因造血干细胞移植后急性移植物抗宿主疾病(aGVHD)的早期准确诊断对患者的预后至关重要。这项研究确定了人类白细胞抗原(HLA)-同种异体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名接受单倍体造血干细胞移植的患者。在这些患者中,有22人在单倍体-PBSCT后出现了aGVHD。结果显示,AGVHD患者的Tim-3+/Perforin+/Granzyme B+CD8+ T细胞水平明显升高,但Galectin-9却明显降低。Galectin-9 和 Tim-3+/Granzyme B+CD8+ T 细胞在 I-II 级 aGVHD 和 III-IV 级 aGVHD 之间的差异也很明显。在体外,Tim-3/Galectin-9 通路激活后,aGVHD 患者 CD8+ T 细胞的凋亡率明显增加,从而减少了 Granzyme B 的分泌。单变量分析显示,Tim-3+CD8+ T 细胞水平是严重 aGVHD 的危险因素。ROC 分析表明,高水平的 Tim-3+CD8+ T 细胞对重度 aGVHD 有显著的诊断价值,曲线下面积为 0.854,临界值为 14.155%。总之,Tim-3与外源性Galectin-9的结合可促进CD8+ T细胞的凋亡,并影响颗粒酶B的分泌。Tim-3+CD8+ T细胞有可能作为免疫学标志物,用于评估单倍体PBSCT后aGVHD的严重程度,并识别严重aGVHD风险较高的患者。
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.
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.
期刊介绍:
The Brazilian Journal of Medical and Biological Research, founded by Michel Jamra, is edited and published monthly by the Associação Brasileira de Divulgação Científica (ABDC), a federation of Brazilian scientific societies:
- Sociedade Brasileira de Biofísica (SBBf)
- Sociedade Brasileira de Farmacologia e Terapêutica Experimental (SBFTE)
- Sociedade Brasileira de Fisiologia (SBFis)
- Sociedade Brasileira de Imunologia (SBI)
- Sociedade Brasileira de Investigação Clínica (SBIC)
- Sociedade Brasileira de Neurociências e Comportamento (SBNeC).