Departments of Clinical Pathology.
Pediatrics, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
J Pediatr Hematol Oncol. 2021 Apr 1;43(3):e320-e327. doi: 10.1097/MPH.0000000000002108.
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 RORγtP<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.
免疫性血小板减少症 (ITP) 的特征是细胞免疫失调。白细胞介素 17 (IL-17)及其分泌细胞 (Th17) 参与了 ITP 的发病机制。维甲酸受体相关孤儿受体 γt (RORγt) 是 Th17 发育的主要调节因子。在 ITP 中， runt 相关转录因子 1 (RUNX1) 与 IL-17 相关基因之间的相互作用仍存在疑问。本研究旨在评估 RUNX1 和 RORγt 与 IL-17A 和 IL-17F 基因在儿童 ITP 中的表达，以研究它们对疾病发病机制和临床表现的贡献。共纳入 90 名儿童，其中 30 名为原发性活动性 ITP 患者，30 名为治疗后缓解的 ITP 患者，30 名为健康对照组。测量了 RUNX1、RORγt、IL-17A 和 IL-17F 基因的表达水平。在活动性 ITP 患者中观察到 RUNX1、RORγt、IL-17A 和 IL-17F 基因的显著过表达，在缓解的 ITP 患者和对照组中均恢复到正常水平 (4 种基因均 P<0.001)。在活动性 ITP 患者中观察到 RUNX1、RORγt、IL-17A 和 IL-17F 表达水平之间存在正相关 (RUNX1 与 RORγt 之间的 P=0.001，RUNX1 与 IL-17A 和 IL-17F 之间的 P<0.001，RORγt 与 IL-17A 之间的 P<0.001，与 IL-17F 之间的 P=0.002，IL-17A 与 IL-17F 之间的 P=0.001)。综上所述，RUNX1 可能通过转录水平上的 RORγt 上调 Th17 分泌细胞因子 IL-17A 和 IL-17F 的表达，参与 ITP 的分子发病机制。因此，靶向 RUNX1 或 RORγt 可能是新的治疗策略。
