Effects of the multidrug resistance-1 gene on drug resistance in primary immune thrombocytopenia. (2nd October 2016)

• Record Type: Journal Article
• Authors: Liu, Wenjie; Li, Huiyuan; Zhang, Donglei; Lv, Mingen; Li, Yang; Hao, Yating; Chen, Yunfei; Liu, Xiaofan; Xue, Feng; Zhang, Lei; Yang, Renchi
• Is Part Of: Autoimmunity. Volume 49:Number 7(2016)
• Page Start: 486
• Page End: 495
• Publication Date: 2016-10-02
• Subjects: P-glycoprotein -- drug resistance -- CD8+ T cells -- cytokine -- apoptosis; Autoimmunity -- Periodicals; Autoimmune diseases -- Periodicals; 571.973
• DOI: 10.1080/08916934.2016.1191476
• Languages: English
• ISSNs: 0891-6934

Abstract

Abstract: Primary immune thrombocytopenia (ITP) is an autoimmune disorder that is characterized by low platelet count. Glucocorticoids (GCs) resistance is a great challenge in the treatment of ITP. P-glycoprotein (P-gp) is a widely studied protein, which is associated with drug resistance. However, in ITP, the functional activity and immune regulation mechanism of P-gp remain uncertain. In this study, we evaluated the expression and functional activity of P-gp in different lymphocyte subsets, explored the correlation between P-gp function and GCs resistance and investigated the role of P-gp in ITP pathogenesis. Results indicated that the functional activity and mRNA level of P-gp were significantly higher in GCs-nonresponsive patients than in GCs-responsive patients with ITP. However, these differences in P-gp were only significant in CD8 + T cells. P-gp function was related to disease activity rather than GCs therapy. P-gp was involved in secreting granzyme B and perforin, maintaining autoreactive lymphocytes survival and enhancing autologous platelets lysis in ITP. In conclusion, over-functional P-gp might play an important role in the pathogenesis of ITP and induce GCs resistance in nonresponsive ITP patients. The blockage of P-gp could be a promising therapeutic approach for GCs-resistant patients with ITP.