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Research Article: Association of TCR?? + double-negative T cells with the response to glucocorticoids in pediatric patients with immune thrombocytopenia

Date Published: 2025-07-30

Abstract:
Pediatric primary immune thrombocytopenia (ITP) is an acquired autoimmune disease that can be partially restored by glucocorticoids. TCR?? + CD4 ? CD8 ? double negative T cells (TCR?? + DNT) has been linked to the pathophysiology of ITP; however, the role of TCR?? + DNT in response to high-dose dexamethasone (HD-DXM) is unclear. In this study, we aimed to explore the alteration in TCR?? + DNT in ITP and the effect of HD-DXM on this subset. Pediatric patients (aged <18 years) newly diagnosed with ITP were recruited for this retrospective study. Th1, Th17, Treg, and TCR?? + DNT levels were measured by flow cytometry using specific antibodies. All patients received HD-DXM treatment and underwent periodic outpatient follow-up for 2-6 months. Patients were divided into the overall response (OR) and no response (NR) groups according to their responses to HD-DXM treatment. We enrolled 130 pediatric patients with ITP (OR, 95 cases; NR, 35 cases) and 50 age- and sex-matched healthy controls. Compared with Th17-to Treg, Th17, and Th1, univariate analysis identified that the proportion of TCR?? + DNT at baseline was more effective in predicting the response to HD-DXM ( P <0.05). A significantly increased frequency of TCR?? + DNT was found in patients with ITP compared to healthy controls (percentage of T cells: 1.31% vs. 1.00%, P <0.0001; percentage of lymphocytes: 0.76% vs. 0.68%, P =0.010). Patients in the NR group had a higher percentage of TCR?? + DNT than the OR at the initial diagnosis (TCR?? + DNT/T: 1.52% vs. 1.30%, P <0.01; TCR?? + DNT/Lym: 0.84% vs. 0.72%, P <0.01). After treatment with HD-DXM, the elevated TCR?? + DNT was effectively reduced in the OR group, but not in the NR group (TCR?? + DNT/T: P <0.05; TCR?? + DNT/Lym: P =0.001; TCR?? + DNT counts: P <0.01). TCR?? + DNT appears to play a significant role in the pathogenesis of pediatric ITP and may be involved in the immune response to HD-DXM. The correction of elevated TCR?? + DNT in patients who respond to HD-DXM may provide a novel insight for immune therapy in pediatric ITP.

Introduction:
Primary immune thrombocytopenia (ITP) is an acquired autoimmune hemorrhagic disease characterized by decreased platelet count due to enhanced platelet destruction and/or impaired platelet production. The estimated incidence of pediatric ITP is 2 to 5 per 100,000 children ( 1 ). Platelet production is a complex biological process that involves the generation and maturation of megakaryocytes, as well as the release of platelets. Platelets originate from megakaryocytes that express many immune receptors and cytokines…

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