Integrating immune profiling and clinical features for early prediction of chronicity in pediatric immune thrombocytopenia

Abstract Pediatric immune thrombocytopenia (ITP) is a heterogeneous autoimmune disorder with variable clinical outcomes. While most children experience spontaneous remission, 10 to 20% progress to chronic ITP. Early prediction to chronicity remains a clinical challenge. This study aimed to develop and validate a logistic regression‐based model integrating immune features to predict chronicity in ITP among children. In this prospective cohort study, we stratified 108 pediatric ITP patients into newly diagnosed with remission ( n = 48), progressors ( n = 13), and chronic ITP ( n = 47). We analyzed peripheral blood using multicolor flow cytometry for 79 immune subsets. We recorded clinical variables including bleeding symptoms, platelet count, and recent infections/vaccinations. We performed multivariable logistic regression using immune parameters alone and in combination with clinical features. Model performance was assessed via 5‐fold cross‐validation and validated on the progressor cohort. Patients with Chronic ITP Exhibited a Distinct Immunological Feature Characterized by Reduced CD4 / CD8 Ratio, naïve Th and naïve Tc Cell and Increased Effector Memory, Tc Cell Percent, Senescent T Cell ( CD57 +, PD1 +), B Memory and Class Switched Memory B Cells. The Immune‐Only Model Identified Reduced naïve Cytotoxic T Cells [ CD8 + CD27 + CD45RA + ] and Increased Double‐Negative B Cells [ CD19 + CD27 − IgD − ] as Key Predictors (Accuracy 71.6%, Area under the Receiver Operating Characteristic Curve ( AUC ) 0.761, p < 0.001), Correctly Classifying 8/13 (61.5%) Progressors. In the Combined Model, Increased Frequencies of Class‐Switched Memory ( CSW ) B Cells [ CD19 + CD27 + IgM ‐ IgD ‐], Terminally Differentiated Effector Cytotoxic [ CD8 + CD28 − ] T Cells, more Specific Double Negative ( DN ) B Cells Population of CD21 ‐/ lowCD38 ‐Cells[ CD19 + CD21 −/Low CD38 ‐ CD27 ‐ IgD ‐] and Clinically, Epistaxis and Absence of Abrupt Onset of Bleeding Were Associated with Chronicity, Improving Overall Accuracy 82.8%, ( AUC 0.905, p < 0.001) and Correctly Classifying 10/13 (76.92%) Progressors. Integration of clinical features with detailed immune profiling enables early and accurate prediction of chronic ITP in children. These findings support its potential in selecting appropriate management strategies warranting validation in larger multicentric cohorts.