Clinical characteristics and decreased CD4+CD25+Foxp3+ regulatory T cells and IL-35 in pediatric immune thrombocytopenia in a single center

TL;DR

This study finds that pediatric immune thrombocytopenia differs from adult cases in age, sex, and immune markers, with reduced regulatory T cells and IL-35 playing a key role.

Contribution

The study identifies a defective Treg/IL-35 axis as a novel pathogenic mechanism in pediatric ITP.

Findings

Pediatric ITP shows a male predominance in the <1 year age group.

IL-35 levels are significantly reduced in pediatric ITP patients.

CD8+ T cells are elevated while Treg cells are decreased in pediatric ITP.

Abstract

Immune thrombocytopenia (ITP) exhibits distinct epidemiological characteristics in terms of age and sex distribution. In contrast to adult ITP, the clinical features and immunological mechanisms underlying pediatric ITP remain incompletely understood.

To analyze the clinical characteristics, treatment response and immunological profiles of newly diagnosed pediatric ITP patients, in order to provide a reference for clinical diagnosis and treatment.

This study enrolled 240 newly diagnosed pediatric ITP patients. Demographic characteristics, predisposing factors, clinical manifestations, treatment response, and prognosis were analyzed. Lymphocyte subsets were assessed by flow cytometry, and serum cytokine levels were measured using ELISA.

The <1 year age group constituted the largest subgroup (51.67%). Gender distribution differed significantly across the age groups (p = 0.005), with a marked male predominance in <1 year group (male-to-female ratio: 2.35:1). A history of vaccination within 1–4 weeks prior to onset was reported in 12.08% of patients, predominantly in the <1 year group (19.35%), whereas 24.58% had a recent history of respiratory infection, most frequently in the 3–6 years group (61.11%). Bleeding manifestations were present in 91.67% of patients, primarily involving the skin and mucous membranes (89.58%), while visceral hemorrhage was rare (5 cases, 2.01%). At the 1-month follow-up, the overall response rate (complete or partial response) reached 99.17%. The long-term (3 years) follow-up revealed a chronic ITP rate of only 8.3%, significantly lower than that in adults. 220 patients (91.67%) received treatment, and treatment selection was age-dependent: the <1 year group primarily received IVIG, whereas the >3 years group more frequently received corticosteroid therapy. Immunological analysis demonstrated an elevated CD8+ T cell proportion (p = 0.001), a decreased Treg cell proportion (p = 0.018), and a reduced CD4+/CD8+ ratio (p = 0.019) in pediatric ITP patients. Cytokine profiling revealed significantly elevated levels of IL-4 (p = 0.039) and IL-10 (p = 0.025), alongside a marked reduction in IL-35 (p = 0.020).

Pediatric ITP demonstrates significant differences from adult ITP in age distribution, sex characteristics, and prognosis. The underlying immune dysregulation involves decreased regulatory T cells, significantly reduced levels of their specific anti-inflammatory cytokine IL-35 and concomitant expansion of CD8+ T cells. The defective Treg/IL-35 axis appears to be a important component in ITP pathogenesis, identifying IL-35 as a promising therapeutic target.