Evaluation of IVIG response in relation to Th1/Th2 cytokines in pediatricm immune thrombocytopenia

Chen, Yuanyuan; Zhou, Yanliang; Zhao, Ning; Zhang, Yao; Xu, Wei-Qun; Tang, Yuanyue

doi:10.1016/j.cyto.2019.05.014

Cited by 7 publications

(5 citation statements)

References 56 publications

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“…Th2 cells mainly secreted IL-4, IL-6, and IL-10, stimulating B cell proliferation to produce antibodies (26). Levels of activated Th17 cells were reported to be elevated in ITP patients, and produced large amounts of IL-17, IL-21, and IL-22 (27,28). In ITP, whether Th1 or Th2 subsets are dominant in mediating pathogenesis is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

et al. 2020

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Immune thrombocytopenia (ITP) is an autoimmune disease which arises due to self-destruction of circulating platelets. Failure to respond or maintain a response to first-line treatment can lead to refractory/relapsed (R/R) ITP. The mechanism remains complicated and lacks a standard clinical treatment. Sirolimus (SRL) is a mammalian target of rapamycin (mTOR) inhibitor that has been demonstrated to inhibit lymphocyte activity, indicating potential for SRL in treatment of ITP. Activation of the mTOR pathway in autoimmune diseases suggests that SRL might be a useful agent for treating ITP. Accordingly, we initiated an open-label, prospective clinical trial using SRL for patients with R/R ITP (ChiCTR-ONC-17012126). The trial enrolled 86 patients, each dosed with 2-4 mg/day of SRL. By the third month, 40% of patients (34 of 86) achieved complete remission (CR) and 45% of patients (39 of 86) achieved partial remission (PR), whereby establishing an overall response rate (ORR) of 85%. By 6 months of treatment, 41% of patients (32 of 78) achieved CR and 29% of patients (23 of 78) achieved PR, establishing an ORR of 70% without serious side effects. After 12 months follow-up, the ORR remained at 65%. We also found that SRL treatment exhibited higher efficacy in achieving CR in ITP patients who were younger than 40 years old or steroid dependent by univariate analysis. Importantly, in patients who responded, SRL treatment was associated with a reduction in the percentage of Th2, Th17 cells, and increase in the percentage of M-MDSCs and Tregs, indicating that SRL may reestablish peripheral tolerance. Taken together, Sirolimus demonstrated efficacy as a second-line agent for R/R ITP.

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Section: Discussionmentioning

confidence: 99%

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

et al. 2020

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“…Cytokines play a crucial role in differentiation of naive CD4 + T cells [57]. Figure 5 shows that aP-GSe enhanced production of not only IFN-γ, IL-2, and IL-12 but also IL-4, IL-6, and IL10, suggesting that both Th1 and Th2 subset cells were activated [58][59][60][61]. Cytokine-cytokine receptor interaction on naive CD4 + T cells activates the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathways, JAK1/2 and STAT1/3/4 induced by IFN-γ and IL-12 to stimulate T-bet and further IFN-γ production, and IL-4 triggers JAK1/3 and STAT6 to activate transcription factors GATA-3 [57].…”

Section: Discussionmentioning

confidence: 99%

A Solution with Ginseng Saponins and Selenium as Vaccine Diluent to Increase Th1/Th2 Immune Responses in Mice

Wang

Cui

et al. 2020

Journal of Immunology Research

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Pseudorabies is an important infectious disease of swine, and immunization using attenuated pseudorabies virus (aPrV) vaccine is a routine practice to control this disease in swine herds. This study was to evaluate a saline solution containing ginseng stem-leaf saponins (GSLS) and sodium selenite (Se) as a vaccine adjuvant for its enhancement of immune response to aPrV vaccine. The results showed that aPrV vaccine diluted with saline containing GSLS-Se (aP-GSe) induced significantly higher immune responses than that of the vaccine diluted with saline alone (aP-S). The aP-GSe promoted higher production of gB-specific IgG, IgG1, and IgG2a, neutralizing antibody titers, secretion of Th1-type (IFN-γ, IL-2, IL-12), and Th2-type (IL-4, IL-6, IL-10) cytokines, and upregulated the T-bet/GATA-3 mRNA expression when compared to aP-S. In addition, cytolytic activity of NK cells, lymphocyte proliferation, and CD4 + /CD8 + ratio was also significantly increased by aP-GSe. More importantly, aP-GSe conferred a much higher resistance of mice to a field virulent pseudorabies virus (fPrV) challenge. As the present study was conducted in mice, further study is required to evaluate the aP-GSe to improve the vaccination against PrV in swine.

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“…5,6) Some studies documented that some cytokines necessary for T helper cells functions (such as interferon gamma [IFN-γ]) were increased in ITP patients. 7,8) Kuwana et al 9) provided evidence of the presence of auto reactive CD4+ T cells that targeted epitopes on GPIIb/IIIa. Programmed cell death protein-1 (PD-1) is an immunoregulatory cell surface molecule that has been assigned as a protein of the Ig-superfamily.…”

Section: Introductionmentioning

confidence: 99%

“…As the presence of autoantibodies is a hallmark of ITP, the involvement of CD4+ T cells in the pathogenesis of ITP have been explored in many studies [ 5 , 6 ]. Some studies documented that some cytokines necessary for T helper cells functions (such as interferon gamma [IFN-γ]) were increased in ITP patients [ 7 , 8 ]. Kuwana et al [ 9 ] provided evidence of the presence of auto reactive CD4+ T cells that targeted epitopes on GPIIb/IIIa.…”

Section: Introductionmentioning

confidence: 99%

Changes and correlations of T-cell coinhibitory molecule programmed death-1 and interferon-γ in pediatric immune thrombocytopenia

et al. 2023

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Background: Immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by abnormalities of T cells subsets. Programmed death-1 (PD-1) is a co-signaling inhibitory molecule in T cells that is involved in many autoimmune diseases.Purpose: Here we aimed to measure changes in PD-1 expression and serum interferon-γ (IFN-γ) levels before and 1 month after treatment in pediatric patients with newly diagnosed ITP.Methods: We measured PD-1+ CD4+ T cells percentages using flow cytometry and the serum IFN-γ levels by enzyme-linked immunosorbent assay in 40 pediatric patients with ITP and 20 healthy controls.Results: Compared with healthy controls, the PD-1+ CD4+ T cells percentages and serum IFN-γ levels were significantly higher in ITP patients before and 1 month after therapy. A correlation study revealed that PD-1+ CD4+ T cells percentage was negatively associated with platelet count and positively associated with IFN-γ level in patients with ITP. Furthermore, serum IFN-γ levels were significantly decreased in patients after treatment, but no significant change was detected in the percentage of PD-1+ CD4+ T cells before or 1 month after therapy.Conclusion: PD-1+ CD4+ T cells expression and IFN-γ levels were increased in patients with ITP. These preliminary data suggest a potential role of PD-1+ CD4+ T cells as mediators of ITP. We also found a correlation between PD-1+ CD4+ T cells and both platelet counts and IFN-γ levels. These findings suggest a potential role of PD-1+ CD4+ T cells and IFN-γ in the pathogenesis of ITP. Further studies investigating PD-1 expression in different T-cell subsets, serum IFN-γ concentrations, and antiplatelet antibodies levels over a longer duration after therapy initiation could delineate the precise role of PD-1 in ITP pathogenesis. Consequently, novel nontraditional therapeutic strategies for ITP patients may become available.

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Evaluation of IVIG response in relation to Th1/Th2 cytokines in pediatricm immune thrombocytopenia

Cited by 7 publications

References 56 publications

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

Sirolimus as Rescue Therapy for Refractory/Relapsed Immune Thrombocytopenia: Results of a Single-Center, Prospective, Single-Arm Study

A Solution with Ginseng Saponins and Selenium as Vaccine Diluent to Increase Th1/Th2 Immune Responses in Mice

Changes and correlations of T-cell coinhibitory molecule programmed death-1 and interferon-γ in pediatric immune thrombocytopenia

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