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

TL;DR

This study shows that TCRαβ+ double-negative T cells are linked to how children with immune thrombocytopenia respond to steroid treatment.

Contribution

The study identifies TCRαβ+DNT as a novel predictor of response to high-dose dexamethasone in pediatric ITP.

Findings

TCRαβ+DNT levels were higher in ITP patients compared to healthy controls.

Non-responders had higher TCRαβ+DNT levels than responders before treatment.

HD-DXM reduced TCRαβ+DNT in responders but not in non-responders.

Abstract

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 (P<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%, P<0.0001; percentage of lymphocytes: 0.76% vs. 0.68%, P=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%, P<0.01; TCRαβ+DNT/Lym: 0.84% vs. 0.72%, P<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: P<0.05; TCRαβ+DNT/Lym: P=0.001; TCRαβ+DNT counts: P<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.

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