Increased Expression of IL-17A and IL-17F Is Correlated With RUNX1 and RORγT in Pediatric Patients With Primary Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is characterized by dysregulated cellular immunity. Interleukin 17 (IL-17) and its secreting cells (Th17) are involved in the pathogenesis of ITP. Retinoic acid receptor–related orphan receptor γt (RORγt) is the chief regulator of Th17 development. The interaction among Runt-related transcription factor 1 (RUNX1) and IL-17-related genes in ITP remains questionable. The study aimed to evaluate the expression of RUNX1 and RORγt together with IL-17A and IL-17F genes in childhood ITP to investigate their contribution to disease pathogenesis and clinical presentation. Ninety children were included, 30 primary active ITP patients, 30 ITP patients in remission after treatment, and 30 healthy controls. The expression levels of RUNX1 , RORγt , IL-17A , and IL-17F genes were measured. Significant overexpression of RUNX1 , RORγt , IL-17A , and IL-17F genes was observed in active ITP patients, which was restored to normal levels in both ITP patients in remission and controls ( P <0.001 for the 4 genes). Positive correlations between RUNX1 , RORγt , IL-17A , and IL-17F expression levels were observed in active ITP patients ( P =0.001 for RUNX1 with RORγt , P <0.001 for RUNX1 with both IL-17A and IL-17F , regarding RORγt P <0.001 with IL-17A and P =0.002 with IL-17F , P =0.001 for IL-17A with IL-17F ). In conclusion, RUNX1 is possibly involved in the molecular pathogenesis of ITP upregulating the expression of Th17-secreted cytokines, IL-17A and IL-17F , through RORγt at the transcriptional level. Thus, targeting RUNX1 or RORγt may be new alternative therapeutic strategies.