HMGB1 is increased in patients with immune thrombocytopenia and negatively associates with Tregs

Zhang, Guoyang; Yang, Peng-Feng; Liu, Xiaoyan; Liu, Hongyun; Wang, Jue; Wang, Jieyu; Xiao, Jie; Nie, Danian; Ma, Liping

doi:10.1016/j.thromres.2022.02.021

Cited by 9 publications

(9 citation statements)

References 34 publications

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“…53 In addition, there was a significant negative correlation between HMGB1 and Foxp3, and the overexpression of HMGB1 was correlated with poor efficacy after splenectomy. 53 They concluded that HMGB1 is associated with the imbalance of T reg /T H 17 cells and is involved in refractoriness of ITP.…”

Section: Ge N Etic M a R K Er Smentioning

confidence: 97%

“…High‐mobility group box 1 protein (HMGB1) is a nuclear protein involved in inflammatory responses and is associated with the development of several autoimmune diseases 52 . Zhang et al 53 studied 20 splenectomized patients with ITP and 19 splenectomized control subjects and measured the expression of HMGB1, RORγt and Foxp3 in the spleen tissues and peripheral blood. They observed that compared with controls, the expression of HMGB1 in the spleens of patients with refractory ITP was significantly higher, while Foxp3 was decreased 53 .…”

Section: Genetic Markersmentioning

confidence: 99%

“…They observed that compared with controls, the expression of HMGB1 in the spleens of patients with refractory ITP was significantly higher, while Foxp3 was decreased 53 . In addition, there was a significant negative correlation between HMGB1 and Foxp3, and the overexpression of HMGB1 was correlated with poor efficacy after splenectomy 53 . They concluded that HMGB1 is associated with the imbalance of T reg /T H 17 cells and is involved in refractoriness of ITP.…”

Section: Genetic Markersmentioning

confidence: 99%

“…Zhang et al 53 studied 20 splenectomized patients with ITP and 19 splenectomized control subjects and measured the expression of HMGB1, RORγt and Foxp3 in the spleen tissues and peripheral blood. They observed that compared with controls, the expression of HMGB1 in the spleens of patients with refractory ITP was significantly higher, while Foxp3 was decreased 53 . In addition, there was a significant negative correlation between HMGB1 and Foxp3, and the overexpression of HMGB1 was correlated with poor efficacy after splenectomy 53 .…”

Section: Genetic Markersmentioning

confidence: 99%

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The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

Yazdanbakhsh,

Provan,

Semple

2023

Br J Haematol

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SummaryImmune thrombocytopenia (ITP) is characterized by a dysregulated immune response against platelets, affecting both their destruction and production. A role for an abnormal T‐cell compartment has been established in ITP pathogenesis and treatments that increase platelet counts in patients with ITP have shown improvements in T‐cell profiles. On the other hand, patients who were refractory to treatment appear to retain the T‐cell abnormalities as before. Myeloid‐derived suppressive cells (MDSCs) are also emerging as key contributors to the immune pathology of ITP and response to treatment. In this review, we will discuss how various treatments affect the T‐cell and MDSC compartments in ITP. The review will focus on studies that have examined the underlying mechanisms and/or genetic basis responsible for refractoriness to a given treatment and highlight remaining challenges in identifying factors and mechanisms to predict response to treatment.

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Section: Ge N Etic M a R K Er Smentioning

confidence: 97%

Section: Genetic Markersmentioning

confidence: 99%

Section: Genetic Markersmentioning

confidence: 99%

Section: Genetic Markersmentioning

confidence: 99%

See 2 more Smart Citations

The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

Yazdanbakhsh,

Provan,

Semple

2023

Br J Haematol

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“…14 , 15 HMGB1 is associated with an imbalance of Treg/Th17 cells and is involved in the pathogenesis of ITP. 16 As 18β-glycyrrhetinic acid (18β-GA) is known to bind to HMGB1 directly, 17 it has been used as a novel pharmacological inhibitor of HMGB1 cytokine activities in several clinical and experimental studies. 18 , 19 18β-GA, the main active metabolite of glycyrrhiza, can be obtained by glucuronidase hydrolysis of glycyrrhiza after oral administration.…”

Section: Introductionmentioning

confidence: 99%

Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia

Wang

et al. 2022

haematol

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Primary immune thrombocytopenia (ITP) is the most common acquired autoimmune bleeding disorder. Abnormally increased levels of High Mobility Group Box 1 Protein (HMGB1) associate with thrombocytopenia and therapeutic outcome in ITP. Previous studies proposed that a natural inhibitor of HMGB1, 18β-glycyrrhetinic acid (18β-GA), has been used for its anti-inflammatory and immune-modulatory effects, although its capability of correcting immune balance in ITP is unclear. In this study, we discovered that plasma HMGB1 correlated negatively with platelet counts in ITP patients, and confirmed that 18β-GA stimulated the production of regulatory T cells (Tregs), restored the balance of CD4+ T cell subsets and enhanced the suppressive function of Tregs through blocking the effect on HMGB1 in patients with ITP. HMGB1 short hairpin RNA interference masked the effect of 18β-GA in Tregs of ITP patients. Furthermore, we found that 18β-GA alleviated thrombocytopenia in ITP mice. Briefly, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to induce a murine model of severe ITP. The proportion of circulating Tregs significantly increased, while the level of plasma HMGB1 and serum antiplatelet antibodies significantly decreased in ITP mice along 18β-GA treatment. In addition, 18β-GA reduced phagocytic activity of macrophages towards platelets both in ITP patients and ITP mice. These results indicated that 18β-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.

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Effect of remote ischemic preconditioning intervention on serum levels of microRNA-582–5p/HMGB1 in patients with acute cerebral infarction

Zhao,

Li,

Yan

et al. 2024

Clinical Neurology and Neurosurgery

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HMGB1 is increased in patients with immune thrombocytopenia and negatively associates with Tregs

Cited by 9 publications

References 34 publications

The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

The role of T cells and myeloid‐derived suppressor cells in refractory immune thrombocytopenia

Enhancing regulatory T-cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia

Effect of remote ischemic preconditioning intervention on serum levels of microRNA-582–5p/HMGB1 in patients with acute cerebral infarction

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