Increased Effector Memory CD4+ T Cells Are Associated with Chronic Childhood Immune Thrombocytopenia

Abstract

BACKGROUND: Antibody- and T-cell immune responses against platelet self-antigens are key features of childhood immune thrombocytopenia (ITP). Reliable diagnostic and prognostic immune markers remain underdeveloped and are not currently used in clinical practice. OBJECTIVES: To validate previously suggested biomarkers and identify novel predictors of chronic childhood ITP. METHODS: We analyzed immune profiles in 158 children with newly diagnosed ITP at the time of diagnosis prior to treatment ("Treatment With or Without IVIg for Kids with ITP" randomized controlled trial). Spontaneous platelet recovery and response to intravenous immunoglobulin were evaluated during 1 year. RESULTS: Neither CD4 +, CD8 +, CD19 +, nor natural killer cell populations predicted the development of chronic ITP or recovery during follow-up. However, we observed a significant age-adjusted increase in effector memory CD4 + T cells by 1.4% (95% CI, 0.4-2.4) in chronic ITP. A frequency of effector memory CD4 + T cells above the median was associated with a reduced likelihood of recovery, with an age- and treatment-adjusted hazard ratio of 0.55 (95% CI, 0.35-0.85). Stratification by effector memory CD4 + T-cell levels demonstrated additional prognostic value over the Childhood ITP Recovery Score, a clinical prediction model. Single-cell RNA-sequencing of peripheral blood mononuclear cells of 6 children confirmed an expansion of effector memory CD4 + T cells in chronic ITP, characterized by high expression of ITGB1 (integrin β1, CD29). CONCLUSIONS: Increased integrin β1-positive effector memory CD4 + T cells are associated with chronic ITP and improve the prognostic value of a clinical prediction model. T-cell phenotyping could be valuable for prognosis and personalized treatment in newly diagnosed childhood ITP.