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Thalidomide induce response in patients with corticosteroid-resistant or relapsed ITP by upregulating Neuropilin-1 expression.

Authors
  • Yang, Zhi-Gang1
  • Wen, Rui-Ting2
  • Zhang, Yu-Ming2
  • Wu, Guo-Cai3
  • Chen, Wei-Juan4
  • Wang, Yu-Feng4
  • Weng, Zhi-Yun4
  • Wen, Si-Si4
  • Zhang, Xiao-Jun4
  • Guan, Mei-Hua3
  • 1 Affiliated Central People's Hospital of Zhanjiang of Guangdong Medical University, Zhanjiang, Guangdong 524045, PR China. Electronic address: [email protected] , (China)
  • 2 Department of Hematology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, Guangdong 524001, PR China. , (China)
  • 3 Affiliated Central People's Hospital of Zhanjiang of Guangdong Medical University, Zhanjiang, Guangdong 524045, PR China. , (China)
  • 4 Guangdong Medical University, Zhanjiang, Guangdong 524023, PR China. , (China)
Type
Published Article
Journal
International immunopharmacology
Publication Date
Jul 01, 2019
Volume
72
Pages
437–444
Identifiers
DOI: 10.1016/j.intimp.2019.04.041
PMID: 31030100
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

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. Copyright © 2019 Elsevier B.V. All rights reserved.

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