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 8 publications

(4 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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“…In a study exploring the role of donor genetic variations in glucocorticoid pathway on steroid responsiveness of GVHD, although donor SNPs in ZAP70 and DUSP1 genes were associated with response, these were not statistically significant on adjustment for multiple testing ( 42 ). Cytokine biomarkers – TLR4 and TNFR1 are significantly increased in steroid-refractory acute GVHD compared to those with steroid-responsive GVHD ( 43 ).…”

Section: Biomarkers For Acute Gvhdmentioning

confidence: 99%

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

Balakrishnan

Kulkarni²,

Pai³

et al. 2023

Front. Immunol.

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Hematopoietic cell transplantation is an established curative treatment option for various hematological malignant, and non-malignant diseases. However, the success of HCT is still limited by life-threatening early complications post-HCT, such as Graft Versus Host Disease (GVHD), Sinusoidal Obstruction Syndrome (SOS), and transplant-associated microangiopathy, to name a few. A decade of research in the discovery and validation of novel blood-based biomarkers aims to manage these early complications by using them for diagnosis or prognosis. Advances in this field have also led to predictive biomarkers to identify patients’ likelihood of response to therapy. Although biomarkers have been extensively evaluated for different complications, these are yet to be used in routine clinical practice. This review provides a detailed summary of various biomarkers for individual early complications post-HCT, their discovery, validation, ongoing clinical trials, and their limitations. Furthermore, this review also provides insights into the biology of biomarkers and the challenge of obtaining a universal cut-off value for biomarkers.

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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 8 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?

Biomarkers for early complications post hematopoietic cell transplantation: Insights and challenges

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