Journal Article

Association of TCRαβ+ double-negative T cells with the response to glucocorticoids in pediatric patients with immune thrombocytopenia

Ma, Jingyao, Wu, Runhui, Chen, Hui, Xie, Xingjuan, Fu, Lingling, Chen, Zhenping

2025

Overview

Pediatric primary immune thrombocytopenia (ITP) is an acquired autoimmune disease that can be partially restored by glucocorticoids. TCRαβ CD4 CD8 double negative T cells (TCRαβ DNT) has been linked to the pathophysiology of ITP; however, the role of TCRαβ DNT in response to high-dose dexamethasone (HD-DXM) is unclear. In this study, we aimed to explore the alteration in TCRαβ 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 TCRαβ 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 TCRαβ DNT at baseline was more effective in predicting the response to HD-DXM ( <0.05). A significantly increased frequency of TCRαβ DNT was found in patients with ITP compared to healthy controls (percentage of T cells: 1.31% vs. 1.00%, <0.0001; percentage of lymphocytes: 0.76% vs. 0.68%, =0.010). Patients in the NR group had a higher percentage of TCRαβ DNT than the OR at the initial diagnosis (TCRαβ DNT/T: 1.52% vs. 1.30%, <0.01; TCRαβ DNT/Lym: 0.84% vs. 0.72%, <0.01). After treatment with HD-DXM, the elevated TCRαβ DNT was effectively reduced in the OR group, but not in the NR group (TCRαβ DNT/T: <0.05; TCRαβ DNT/Lym: =0.001; TCRαβ DNT counts: <0.01). TCRαβ 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 TCRαβ DNT in patients who respond to HD-DXM may provide a novel insight for immune therapy in pediatric ITP.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Autoimmune diseases / Blood platelets / CD4 antigen / CD8 antigen / Child / Child, Preschool / Cytokines / Dexamethasone / Dexamethasone - therapeutic use / double-negative T cell / Female / Flow cytometry / glucocorticoid / Glucocorticoids / Glucocorticoids - therapeutic use / Graft versus host disease / Helper cells / high-dose dexamethasone / Humans / Idiopathic thrombocytopenic purpura / immune thrombocytopenia / Immunology / Lymphocytes / Lymphocytes T / Male / Pathogenesis / Patients / pediatric / Pediatrics / Purpura, Thrombocytopenic, Idiopathic - diagnosis / Purpura, Thrombocytopenic, Idiopathic - immunology / Receptors, Antigen, T-Cell, alpha-beta - immunology / Retrospective Studies / T-Lymphocytes, Cytotoxic - immunology / Thrombocytopenia / Treatment Outcome / Tumor necrosis factor-TNF