The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP

Takahashi, Noriyuki; Saitoh, Takayuki; Gotoh, Nanami; Nitta, Yasuhiro; Alkebsi, Lobna; Kasamatsu, Tetsuhiro; Minato, Yusuke; Yokohama, Akihiko; Tsukamoto, Norifumi; Handa, Hiroshi; Murakami, Hirokazu

doi:10.1186/s12865-017-0210-3

Cited by 40 publications

(27 citation statements)

References 37 publications

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“…It is widely accepted that naive CD4 + T cells can differentiate into helper T cells such as Th1, Th2, Th9, Th17, and Th22 cells, and the Th1/Th2 imbalance plays an important role in the asthmatic airway (14,28,29). In the OVA exposure experiment, compared with control group, serum IL-4 levels were significantly higher in OVA-induced asthmatic mice, whereas serum IFN-γ levels and the IFN-γ/IL-4 ratio were obviously decreased, indicating that Th1/Th2 balance was disturbed in OVA-induced asthmatic mice (30). It is generally thought that cytokines, IL-12 and IL-4, are crucial for Th1 and Th2 cell differentiation, respectively (31).…”

Section: Discussionmentioning

confidence: 94%

Lipoxin A4 regulates PM2.5-induced severe allergic asthma in mice via the Th1/Th2 balance of group 2 innate lymphoid cells

Han

et al. 2018

J. Thorac. Dis.

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Section: Discussionmentioning

confidence: 94%

Lipoxin A4 regulates PM2.5-induced severe allergic asthma in mice via the Th1/Th2 balance of group 2 innate lymphoid cells

Han

et al. 2018

J. Thorac. Dis.

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“…However, T helper (Th) cells compose a broad group of immune cells that includes T helper 1 (Th1) cells, T helper 2 (Th2) cells, T helper 17 (Th17) cells, and T regulatory (Treg) cells. Th1/Th2 and Th17/Treg cell imbalances have been confirmed in ITP patients 3 , 4 . Additionally, the imbalances between these T cells result in an inflammatory state, which contributes to vascular endothelial injury and platelet destruction in ITP patients.…”

Section: Introductionmentioning

confidence: 82%

Predicting bleeding risk in a Chinese immune thrombocytopenia (ITP) population: development and assessment of a new predictive nomogram

Wang

Liu

et al. 2020

Sci Rep

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The aim of this study was to develop a model that could be used to forecast the bleeding risk of ITP based on proinflammatory and anti-inflammatory factors. One hundred ITP patients were recruited to build a new predictive nomogram, another eighty-eight ITP patients were enrolled as validation cohort, and data were collected from January 2016 to January 2019. Four demographic characteristics and fifteen clinical characteristics were taken into account. Eleven cytokines (IFN-γ, IL-1, IL-4, IL-6, IL-8, IL-10, IL-17A, IL-22, IL-23, TNF-α and TGF-β) were used to study and the levels of them were detected by using a cytometric bead array (CBA) human inflammation kit. The least absolute shrinkage and selection operator regression model was used to optimize feature selection. Multivariate logistic regression analysis was applied to build a new predictive nomogram based on the results of the least absolute shrinkage and selection operator regress ion model. The application of C-index, ROC curve, calibration plot, and decision curve analyses were used to assess the discrimination, calibration, and clinical practicability of the predictive model. Bootstrapping validation was used for testing and verifying the predictive model. After feature selection, cytokines IL-1, IL-6, IL-8, IL-23 and TGF-β were excluded, cytokines IFN-γ, IL-4, IL-10, IL-17A, IL-22, TGF-β, the count of PLT and the length of time of ITP were used as predictive factors in the predictive nomogram. The model showed good discrimination with a C-index of 0.82 (95% confidence interval 0.73376–0.90 624) in training cohortn and 0.89 (95% CI 0.868, 0.902) in validation cohort, an AUC of 0.795 in training cohort, 0.94 in validation cohort and good calibration. A high C-index value of 0.66 was reached in the interval validation assessment. Decision curve analysis showed that the bleeding risk nomogram was clinically useful when intervention was decided at the possibility threshold of 16–84%. The bleeding risk model based on IFN-γ, IL-4, IL-10, IL-17A, IL-22, TGF-β, the count of PLT and the length of time of ITP could be conveniently used to predict the bleeding risk of ITP.

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“…8 Loss of immune tolerance plays a crucial role in the pathogenesis of ITP, manifested with imbalance of Th1/Th2 and Th17/Tregs, dysfunction of cytotoxic T lymphocytes (CTLs) and NK cells. [43][44][45][46] Monocytes and macrophages are the major cells involved in platelet destruction in the reticuloendothelial system. Surgical splenectomy has been the second-line treatment of ITP for decades with a response rate of 60 to 70%.…”

Section: Discussionmentioning

confidence: 99%

Tumor Necrosis Factor-α Blockade Corrects Monocyte/Macrophage Imbalance in Primary Immune Thrombocytopenia

Zhao

Guo

et al. 2021

Thromb Haemost

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Primary immune thrombocytopenia (ITP) is an acquired autoimmune bleeding disorder. Monocytes and macrophages are the major cells involved in autoantibody-mediated platelet clearance in ITP. In the present study, we found increased percentages of peripheral blood proinflammatory CD16+ monocytes and elevated frequencies of splenic tumor necrosis factor-α (TNF-α)-expressing macrophages in ITP patients compared with healthy controls. Concurrently, we observed elevated TNF-α secretion in plasma as well as higher TNF-α mRNA expression in total peripheral blood mononuclear cells and CD14+ monocytes of ITP patients. Of note, in vitro TNF-α blockade with neutralizing antibody remarkably reduced polarization to M1 macrophages by inhibiting the nuclear factor kappa B (NF-κB) signaling pathway. Moreover, TNF-α blockade dampened macrophage phagocytosis and T cell stimulatory capacity. Finally, in passive and active murine models of ITP, anti-TNF-α therapy reduced the number of nonclassical monocytes and M1 macrophages, ameliorated the retention of platelets in spleen and liver, and increased the platelet count of ITP mice. Taken together, TNF-α blockade decreased the number and function of proinflammatory subsets of monocytes and macrophages by inhibiting the NF-κB signaling pathway, leading to remarkable attenuation of antibody-mediated platelet destruction. Thus, TNF-α blockade may be a promising therapeutic strategy for the management of ITP.

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The cytokine polymorphisms affecting Th1/Th2 increase the susceptibility to, and severity of, chronic ITP

Cited by 40 publications

References 37 publications

Lipoxin A4 regulates PM2.5-induced severe allergic asthma in mice via the Th1/Th2 balance of group 2 innate lymphoid cells

Lipoxin A4 regulates PM2.5-induced severe allergic asthma in mice via the Th1/Th2 balance of group 2 innate lymphoid cells

Predicting bleeding risk in a Chinese immune thrombocytopenia (ITP) population: development and assessment of a new predictive nomogram

Tumor Necrosis Factor-α Blockade Corrects Monocyte/Macrophage Imbalance in Primary Immune Thrombocytopenia

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