A panel of 4 biomarkers for the early diagnosis and therapeutic efficacy of aGVHD

Li, Xiaoping; Chen, Ting; Gao, Qiangguo; Zhang, Wei; Xiao, Yunshuo; Zhu, Wen; Zeng, Lingyu; Li, Zhenyu; Yang, Shijie; Wang, Rui; Wang, Xiaoqi; Feng, Yimei; Zhang, Xi

doi:10.1172/jci.insight.130413

Cited by 11 publications

(5 citation statements)

References 28 publications

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“…The present study showed that p53 was significantly downregulated in CD4 + T cells from patients with aGVHD compared with the non-aGVHD group. Moreover, other studies have confirmed that IL-2 is significantly increased in both aGVHD mouse models and patients ( 26 ). These findings suggest that CD4 + T cells with insufficient p53 expression are over-activated and proliferate under stimulation by large amounts of IL-2, mediating inflammatory damage in various organs in aGVHD patients.…”

Section: Discussionmentioning

confidence: 76%

Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

Hua

Chen

et al. 2020

Front. Immunol.

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Recent evidence indicates that p53 plays a protective role against various systemic autoimmune diseases by suppressing pro-inflammatory cytokine production and reducing the number of pathogenic T cells. However, whether abnormal p53 expression participates in the development of acute graft-versus-host disease (aGVHD) remains unclear. In this study, we demonstrated that p53 was downregulated in CD4 + T cells from patients with aGVHD compared with the non-aGVHD group. Furthermore, we confirmed that low expression of CCCTC-binding factor (CTCF) in CD4 + T cells from aGVHD cases is an important factor affecting histone H3K9/K14 hypoacetylation in the p53 promoter and p53 downregulation. Restoring CTCF expression in CD4 + T cells from aGVHD patients increased p53 amounts and corrected the imbalance of Th17 cells/Tregs. Taken together, these results provide novel insights into p53 downregulation in CD4 + T cells from aGVHD patients.

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Section: Discussionmentioning

confidence: 76%

Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

Hua

Chen

et al. 2020

Front. Immunol.

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“…In our study, patients transplanted with SC grafts mobilized with pegfilgrastim achieved neutrophil and platelet engraftment after a median of 14.5 and 15 days, respectively, which was similar to the results of other studies of pegfilgrastim- and G-CSF-induced mobilization ( 9 ). GVHD is still one of the major causes of morbidity and mortality in allograft recipients, with a high incidence of 30–50% and a 14% mortality rate ( 31 ). We observed that the incidence of aGVHD was 26.3%.…”

Section: Discussionmentioning

confidence: 99%

Is It Better to Mobilize Hematopoietic Stem Cells With Pegfilgrastim in Healthy Donors During Allogeneic Hematopoietic Stem Cell Transplantation?

Wang²,

Zhang

et al. 2020

Front. Oncol.

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“…Li et al [40] conducted research in patients who had already onset aGVHD, that compared with patients without aGVHD, the expression of IL-2, IL-4, IL-10 and IL-17A were significantly increased. Furthermore, IL-6 level was extremely high in patients with III-IV aGVHD compared with I-II aGVHD.…”

Section: Discussionmentioning

confidence: 99%

Can Cytokine Detection Predict the Occurrence and Outcome of aGVHD after Allo-HCT? A Retrospective Study

Gao¹,

Zhang²,

Zeng³

et al. 2023

Discovery Medicine

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Background: Many cytokines play essential roles in the occurrence and development of acute graft-versus-host-disease (aGVHD). This study aims to validate whether 11 proinflammatory and anti-inflammatory cytokines can be a candidate for aGVHD biomarkers to predict its occurrence and outcome. Methods: Out of 178 patients who underwent allogeneic hematopoietic stem cell transplantation, we retrospectively enrolled 32 cases into the pre-transplant cohort and 45 cases into the post-transplant cohort. The serum cytokine concentrations were determined by flow cytometry. The control and experimental groups were non-aGVHD, I-II aGVHD and III-IV aGVHD groups, respectively. Risk factors and overall survival (OS) were also evaluated. Results: In the pre-transplant cohort, interleukin (IL)-2 decreased in patients with aGVHD, and IL-4 only reduced in patients with III-IV aGVHD. In the post-transplant cohort, only IL-4 increased 1.79 times more in patients with III-IV aGVHD than in the other two groups. Patients with gastrointestinal (GI) aGVHD had lower IL-2, IL-4 and IL-17F levels pre-transplant and lower IL-2 post-transplant. None of the other cytokines was significantly different. Logistic regression analysis showed that no cytokine could predict the occurrence and outcome of aGVHD. Diarrhea within 15 days post-transplant is an independent risk factor for the occurrence of aGVHD and a risk factor for a fatal outcome. Patients without diarrhea had longer survival time of 672 (586-757) days vs 444 (229-548) days and better 2-year OS (85.7% vs 46.4%) than those with diarrhea. Compared to patients with aGVHD, patients without aGVHD had a longer survival time of 618 (530-706) days vs 449 (353-545) days and better 2-year OS (76.2% vs 47.1%). Conclusions: Proinflammatory and anti-inflammatory cytokines can provide specific indications for the occurrence and progression of aGVHD. However, to truly guide the diagnosis and prognosis, cytokines with larger sample sizes, more detection time points and more accurate diagnostic efficacy need to be further studied.

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A panel of 4 biomarkers for the early diagnosis and therapeutic efficacy of aGVHD

Abstract: Role of funding source: All funding sources were used to purchase experimental reagents and mice and to pay for protein microarray analysis.

Cited by 11 publications

References 28 publications

Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

Downregulation of p53 by Insufficient CTCF in CD4+ T Cells Is an Important Factor Inducing Acute Graft-Versus-Host Disease

Is It Better to Mobilize Hematopoietic Stem Cells With Pegfilgrastim in Healthy Donors During Allogeneic Hematopoietic Stem Cell Transplantation?

Can Cytokine Detection Predict the Occurrence and Outcome of aGVHD after Allo-HCT? A Retrospective Study

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