MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages

Cao, Jingjing; Ji, Lili; Zhan, Yanxia; Shao, Xia; Xu, Pengcheng; Wu, Boting; Chen, Pu; Cheng, Luya; Zhuang, Xibing; Ou, Yang; Hua, Fanli; Sun, Lihua; Li, Feng; Chen, Hao; Zhou, Zhaocai; Cheng, Yunfeng

doi:10.1038/s41423-023-01089-8

Cited by 11 publications

(2 citation statements)

References 57 publications

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“…5,6 New treatments for refractory ITP are being explored. [7][8][9] The traditional concept of the pathophysiology of ITP is that antibody-coated platelets are destroyed by interaction with Fcγ receptors. 10 However, as anti-platelet antibodies only can be detected in half of the patients, alternative mechanisms of platelet destruction are also involved, including the reduction in the numbers and function of regulatory T cells, 11,12 the destruction of platelets by CD8 + T cells 13 and epigenetic alteration.…”

Section: Backgrou N Dsmentioning

confidence: 99%

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses

Ou,

Zhan,

Shao

et al. 2023

Br J Haematol

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SummaryPrimary immune thrombocytopenia (ITP) is an acquired autoimmune disease. Cellular and systemic lipid metabolism plays a significant role in the regulation of immune cell activities. However, the role of lipoprotein lipids and apolipoproteins in ITP remains elusive. The automatic biochemistry analyser was used to measure the levels of serum total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A‐I (apoA‐I), apoB, apoE and lipoprotein a [LP(a)]. Genetic variants strongly associated with circulating lipoprotein lipids and apolipoproteins (LDL‐C, apoB, TG, HDL‐C and apoA‐I) were extracted to perform Mendelian randomization (MR) analyses. Finally, drug‐target MR and passive ITP mice model was used to investigate the potential druggable targets of ITP. Levels of HDL‐C, apoA‐I, decreased and LP(a) increased in ITP patients compared with healthy controls. Low HDL‐C was causally associated with ITP susceptibility. Through drug‐target MR and animal modelling, ABCA1 was identified as a potential target to design drugs for ITP. Our study found that lipid metabolism is related to ITP. The causative association between HDL‐C and the risk of ITP was also established. The study provided new evidence of the aetiology of ITP. ABCA1 might be a potential drug target for ITP.

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Section: Backgrou N Dsmentioning

confidence: 99%

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses

Ou,

Zhan,

Shao

et al. 2023

Br J Haematol

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“…Primary immune thrombocytopenia (ITP), an acquired autoimmune bleeding disorder, displays diverse characteristics of heterogeneity ( 1 ), chronicity ( 2 ), asymptomatic nature ( 3 ), and severity ( 4 ). As the global population ages, there is a discernible increase in the quantity of ITP cases.…”

Section: Introductionmentioning

confidence: 99%

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

Zhang,

Huang,

Thomas

et al. 2024

Front. Immunol.

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Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of platelets. Although it was long believed that the critical role of autoantibodies in platelet destruction, primarily through the Fc-dependent platelet clearance pathway, recent findings indicate that the significance of the Fc-independent platelet clearance pathway mediated by hepatocytes, thus shedding light on a previously obscure aspect of ITP pathogenesis. Within this context, the desialylation of platelets has emerged as a pivotal biochemical marker. Consequently, targeting platelet desialylation emerges as a novel therapeutic strategy in the pathogenesis of ITP. Notably, prevailing research has largely focused on antiplatelet antibodies and the glycosylation-associated mechanisms of platelet clearance, while comprehensive analysis of platelet desialylation remains scant. In response, we retrospectively discuss the historical progression, inducing factors, generation process, and molecular regulatory mechanisms underlying platelet desialylation in ITP pathogenesis. By systematically evaluating the most recent research findings, we contribute to a comprehensive understanding of the intricate processes involved. Moreover, our manuscript delves into the potential application of desialylation regulatory strategies in ITP therapy, heralding novel therapeutic avenues. In conclusion, this manuscript not only fills a critical void in existing literature but also paves the way for future research by establishing a systematic theoretical framework. By inspiring new research ideas and offering insights into the development of new therapeutic strategies and targeted drugs, our study is poised to significantly advance the clinical management of ITP.

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Autoimmune effector mechanisms associated with a defective immunosuppressive axis in immune thrombocytopenia (ITP)

Li,

Marcoux,

et al. 2024

Autoimmunity Reviews

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MST4 kinase regulates immune thrombocytopenia by phosphorylating STAT1-mediated M1 polarization of macrophages

Cited by 11 publications

References 57 publications

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses

Lipoprotein lipids and apolipoproteins in primary immune thrombocytopenia: Results from a clinical characteristics and causal relationship verification, potential drug target identification by Mendelian randomization analyses

The role of platelet desialylation as a biomarker in primary immune thrombocytopenia: mechanisms and therapeutic perspectives

Autoimmune effector mechanisms associated with a defective immunosuppressive axis in immune thrombocytopenia (ITP)

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