Children's Hospital, Hematology Unit.
Department of Clinical Pathology.
J Pediatr Hematol Oncol. 2022 Jan 1;44(1):e96-e100. doi: 10.1097/MPH.0000000000002160.
Dexamethasone is approved as second-line therapy in pediatric chronic immune thrombocytopenic purpura (ITP). Several B-cell abnormalities have been described in ITP pathogenesis.This study assessed the effects of high-dose dexamethasone (HD-DXM) on the percentages and absolute counts of CD19+CD24hiCD38hi regulatory (Bregs) and CD19+CD27+ memory B lymphocytes (Bmems) in children with chronic ITP during active bleeding.The study was a prospective case-control, included 20 children with chronic ITP and uncontrolled bleeding. Children received a single daily dose of HD-DXM for 4 days. Blood samples were withdrawn from patients just before HD-DXM therapy and on day 5 to evaluate the platelet counts and flow cytometric analysis of Bregs and Bmem. The patients' platelet counts significantly increased after 5 days of the initiation of therapy (P=0.0001). Bmems percentage and absolute counts were significantly higher in patients before treatment (P=0.0007), and decreased after HD-DXM therapy (P=0.97) compared with the controls. Bregs percentage and absolute counts were significantly lower before treatment (P=0.0003) and increased after HD-DXM (P=0.003). There is a negative correlation between platelet counts and Bregs percentage and absolute count Bmems percentage before and after HD-DXM, whereas a positive correlation between platelets and Bregs before and after dexamethasone has been reported.
HD-DXM reestablishes the normal Bregs/Bmems balance. This finding discloses possible involvement of Bregs and Bmems in the pathogenesis of pediatric ITP and provides a novel vision for immune modulation and treatment perspectives.
地塞米松已被批准用于儿童慢性免疫性血小板减少性紫癜(ITP)的二线治疗。ITP 发病机制中已描述了几种 B 细胞异常。本研究评估了大剂量地塞米松(HD-DXM)对处于活动性出血期的慢性 ITP 儿童的 CD19+CD24hiCD38hi 调节性 B 细胞(Bregs)和 CD19+CD27+记忆 B 淋巴细胞(Bmems)的百分比和绝对计数的影响。该研究为前瞻性病例对照研究,纳入 20 例慢性 ITP 且伴有未控制出血的患儿。患儿接受为期 4 天的每日一次的 HD-DXM 治疗。在开始 HD-DXM 治疗前和第 5 天从患者中抽取血样,以评估血小板计数和 Bregs 和 Bmem 的流式细胞术分析。治疗开始后 5 天患者的血小板计数显著增加(P=0.0001)。治疗前患者的 Bmems 百分比和绝对计数显著更高(P=0.0007),而治疗后下降(P=0.97),与对照组相比。治疗前 Bregs 百分比和绝对计数显著更低(P=0.0003),治疗后增加(P=0.003)。HD-DXM 治疗前后血小板计数与 Bregs 百分比和绝对计数、Bmems 百分比呈负相关,而地塞米松治疗前后血小板计数与 Bregs 呈正相关。
HD-DXM 重建了正常的 Bregs/Bmems 平衡。这一发现揭示了 Bregs 和 Bmems 可能参与了儿童 ITP 的发病机制,并为免疫调节和治疗提供了新的视角。