Department of Hematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany; Department of Hematology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Department of Hematology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China.
Thromb Res. 2022 Oct;218:157-168. doi: 10.1016/j.thromres.2022.08.014. Epub 2022 Aug 18.
Dexamethasone (DXM) or immunoglobulin (IVIg) are first-line therapies for primary immune thrombocytopenia (ITP), with an effective rate of 80 %. Some patients with both severe bleeding symptoms and platelet counts of <30 × 10/L received a combination of DXM and IVIg. Autoimmune disorders, especially involving CD4 T-cells, play a key role in the pathogenesis of ITP. We assumed that variations in the immune status of CD4 T-cells will lead to different treatment responses. Until now, there have been few relevant clinical studies on CD4 T-cells and the outcome of first-line therapies.
A prospective study enrolling 42 newly diagnosed ITP patients and 30 normal control volunteers was performed. The profiles of major CD4 T-cells, including T helper (Th)1, Th2, Th17, and regulatory T (Treg) cells, and the related levels of interleukin (IL)-2, IL-17, and IL-23 were examined. The platelet number was recorded at the time point of day 0, day 14, and day 30.
Greater concentrations of Th1 and Th17 cells and lower relative numbers of Treg cells were found in the ITP group. As for the treatment outcome on day 14, the profiles of Th2 and IL-2 were significantly greater in the NR group, while the expression of IL-17 was elevated in the CR group. As for the treatment outcome on day 30, higher levels of Th2 cells were observed in those patients who needed 2× pulses of HD DXM compared to those who needed only 1× pulse of HD DXM and IVIg, and receiver operating characteristic curve analysis showed that lower Treg cell may predict favorable values. Meanwhile, the higher IL-23 value may predict a poor early response.
Our results indicate that Th1, Th17, and Treg cells and IL-2 and IL-23 participate in the onset of ITP. Higher profiles of Th2, IL-2 and IL-23 may predict poor treatment outcomes. Higher levels of IL-17 and lower profile of Treg may predict sensitivity to HD DXM and IVIg combination therapy.
地塞米松（DXM）或免疫球蛋白（IVIg）是成人原发免疫性血小板减少症（ITP）的一线治疗药物，有效率为 80%。一些有严重出血症状且血小板计数<30×10/L 的患者接受了 DXM 和 IVIg 的联合治疗。自身免疫性疾病，尤其是涉及 CD4 T 细胞的自身免疫性疾病，在 ITP 的发病机制中起着关键作用。我们假设 CD4 T 细胞的免疫状态的变化将导致不同的治疗反应。到目前为止，关于 CD4 T 细胞和一线治疗结果的相关临床研究很少。
对 42 例新诊断的 ITP 患者和 30 名正常对照志愿者进行前瞻性研究。检测主要 CD4 T 细胞（Th1、Th2、Th17 和调节性 T 细胞[Treg]）的表型，以及白细胞介素（IL）-2、IL-17 和 IL-23 的相关水平。在第 0、14 和 30 天记录血小板计数。
ITP 组中 Th1 和 Th17 细胞浓度较高，Treg 细胞相对数量较低。在第 14 天的治疗结果方面，NR 组的 Th2 和 IL-2 明显较高，而 CR 组的 IL-17 表达升高。在第 30 天的治疗结果方面，与仅接受 1 次高剂量地塞米松（HD DXM）和 IVIg 治疗的患者相比，需要 2 次 HD DXM 脉冲治疗的患者 Th2 细胞水平更高，受试者工作特征曲线分析显示，Treg 细胞水平较低可能预示着更好的疗效。同时，较高的 IL-23 值可能预示着早期反应不佳。
我们的结果表明，Th1、Th17 和 Treg 细胞以及 IL-2 和 IL-23 参与了 ITP 的发病机制。较高的 Th2、IL-2 和 IL-23 水平可能预示着治疗效果不佳。较高的 IL-17 和较低的 Treg 水平可能预示着对 HD DXM 和 IVIg 联合治疗的敏感性。
