Affiliated Central People's Hospital of Zhanjiang of Guangdong Medical University, Zhanjiang, Guangdong 524045, PR China.
Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, PR China.
Int Immunopharmacol. 2019 Jul;72:437-444. doi: 10.1016/j.intimp.2019.04.041.
Immune thrombocytopenia (ITP) is an immune-mediated acquired autoimmune hemorrhagic disease. About one-third of patients are unresponsive to first-line therapies. Thalidomide (THD) as an immunomodulatory agent is now used to treat several autoimmune disorders. Therefore, we assessed the safety and efficacy of THD in corticosteroid-resistant or relapsed ITP patients, and preliminarily explore its mechanism.
50 newly-diagnosed ITP patients and 47 healthy volunteers were enrolled in this study. Additionally, 17 corticosteroid-resistant or relapsed ITP patients were recruited, with 7 cases in the rhTPO + THD group and 10 cases in the THD monotherapy group. Overall response rate at 6, 12, and 24 months were assessed. Levels of Neuropilin-1(NRP-1), regulatory T cells (Tregs) and regulatory B cells (Bregs) were detected.
Expression of NRP-1, Tregs and Bregs were reduced in newly-diagnosed ITP patients. In vitro, THD treatment upregulated expression of NRP-1and Tregs only in ITP patients. As for corticosteroid-resistant or relapsed ITP patients, overall response rate at 6, 12, and 24 months was 85.7%, 57.1% and 100% in the rhTPO + THD group and 60%, 75% and 83.3% in the THD group, respectively. Additionally, rhTPO plus THD or THD therapy significantly increased the levels of NRP-1, Tregs and Bregs in responders.
Our study shows for the first time that NRP-1 is involved in the pathogenesis of ITP, THD could induce response in ITP patients by upregulating NRP-1 expression and restoring the proportion of Tregs and Bregs. THD might be served as a novel therapeutic agent in corticosteroid-resistant or relapsed ITP patients.
免疫性血小板减少症（ITP）是一种由免疫介导的获得性自身免疫性出血性疾病。约三分之一的患者对一线治疗无反应。沙利度胺（THD）作为一种免疫调节剂，现已用于治疗多种自身免疫性疾病。因此，我们评估了 THD 在皮质激素抵抗或复发 ITP 患者中的安全性和疗效，并初步探讨了其机制。
本研究纳入了 50 例新诊断的 ITP 患者和 47 名健康志愿者。此外，还招募了 17 例皮质激素抵抗或复发的 ITP 患者，其中 7 例在 rhTPO+THD 组，10 例在 THD 单药组。评估了 6、12 和 24 个月时的总缓解率。检测了 Neuropilin-1（NRP-1）、调节性 T 细胞（Tregs）和调节性 B 细胞（Bregs）的水平。
新诊断的 ITP 患者中 NRP-1、Tregs 和 Bregs 的表达降低。体外，THD 治疗仅在 ITP 患者中上调 NRP-1 和 Tregs 的表达。对于皮质激素抵抗或复发的 ITP 患者，rhTPO+THD 组的 6、12 和 24 个月的总缓解率分别为 85.7%、57.1%和 100%，THD 组分别为 60%、75%和 83.3%。此外，rhTPO 联合 THD 或 THD 治疗可显著提高缓解者 NRP-1、Tregs 和 Bregs 的水平。
本研究首次表明 NRP-1 参与了 ITP 的发病机制，THD 通过上调 NRP-1 表达并恢复 Tregs 和 Bregs 的比例，可诱导 ITP 患者产生反应。THD 可能成为皮质激素抵抗或复发 ITP 患者的一种新的治疗药物。
