Chen Hui, Xie Xingjuan, Ma Jingyao, Fu Lingling, Wu Runhui, Chen Zhenping
Department of Clinical Laboratory Center, National Key Clinical Discipline of Pediatric Hematology, National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Hematology Center, National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
Front Immunol. 2025 Jul 30;16:1645932. doi: 10.3389/fimmu.2025.1645932. eCollection 2025.
Pediatric primary immune thrombocytopenia (ITP) is an acquired autoimmune disease that can be partially restored by glucocorticoids. TCRαβCD4CD8 double negative T cells (TCRαβDNT) has been linked to the pathophysiology of ITP; however, the role of TCRαβDNT in response to high-dose dexamethasone (HD-DXM) is unclear. In this study, we aimed to explore the alteration in TCRαβDNT 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 TCRαβDNT 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 TCRαβDNT at baseline was more effective in predicting the response to HD-DXM (<0.05). A significantly increased frequency of TCRαβDNT 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 TCRαβDNT than the OR at the initial diagnosis (TCRαβDNT/T: 1.52% vs. 1.30%, <0.01; TCRαβDNT/Lym: 0.84% vs. 0.72%, <0.01). After treatment with HD-DXM, the elevated TCRαβDNT was effectively reduced in the OR group, but not in the NR group (TCRαβDNT/T: <0.05; TCRαβDNT/Lym: =0.001; TCRαβDNT counts: <0.01).
TCRαβDNT 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 TCRαβDNT in patients who respond to HD-DXM may provide a novel insight for immune therapy in pediatric ITP.
儿童原发性免疫性血小板减少症（ITP）是一种获得性自身免疫性疾病，糖皮质激素可使其部分恢复。TCRαβCD4CD8双阴性T细胞（TCRαβDNT）与ITP的病理生理学相关；然而，TCRαβDNT在高剂量地塞米松（HD-DXM）治疗反应中的作用尚不清楚。在本研究中，我们旨在探讨ITP中TCRαβDNT的变化以及HD-DXM对该亚群的影响。
本回顾性研究纳入新诊断为ITP的儿科患者（年龄<18岁）。使用特异性抗体通过流式细胞术检测Th1、Th17、调节性T细胞（Treg）和TCRαβDNT水平。所有患者均接受HD-DXM治疗，并进行为期2 - 6个月的定期门诊随访。根据患者对HD-DXM治疗的反应分为总体缓解（OR）组和无反应（NR）组。
我们纳入了130例儿科ITP患者（OR组95例；NR组35例）和50例年龄及性别匹配的健康对照。与Th17与Treg、Th17和Th1相比，单因素分析发现基线时TCRαβDNT的比例在预测HD-DXM治疗反应方面更有效（<0.05）。与健康对照相比，ITP患者中TCRαβDNT的频率显著增加（T细胞百分比：1.31%对1.00%，<0.0001；淋巴细胞百分比：0.76%对0.68%，=0.010）。NR组患者在初始诊断时TCRαβDNT的百分比高于OR组（TCRαβDNT/T：1.52%对1.30%，<0.01；TCRαβDNT/Lym：0.84%对0.72%，<0.01）。HD-DXM治疗后，OR组中升高的TCRαβDNT有效降低，而NR组未降低（TCRαβDNT/T：<0.05；TCRαβDNT/Lym：=0.001；TCRαβDNT计数：<0.01）。
TCRαβDNT似乎在儿童ITP的发病机制中起重要作用，可能参与对HD-DXM的免疫反应。纠正对HD-DXM有反应患者中升高的TCRαβDNT可能为儿童ITP的免疫治疗提供新的见解。
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