1. Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness.
- Author
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Wang S, Guan Y, Wang Y, Li H, Zhang D, Ju M, Hao Y, Song X, Sun B, Dou X, and Yang R
- Subjects
- Adolescent, Adult, Antibodies, Anti-Idiotypic pharmacology, Antigens, Human Platelet immunology, Autoantibodies blood, Autoantibodies immunology, B-Lymphocyte Subsets metabolism, CD40 Ligand pharmacology, Cells, Cultured, Female, Humans, Interleukin-2 pharmacology, Interleukins pharmacology, Lymphocyte Activation, Male, Organometallic Compounds pharmacology, PTEN Phosphohydrolase antagonists & inhibitors, PTEN Phosphohydrolase blood, PTEN Phosphohydrolase physiology, Plasma Cells drug effects, Platelet Count, Purpura, Thrombocytopenic, Idiopathic blood, Purpura, Thrombocytopenic, Idiopathic drug therapy, RNA, Messenger blood, Receptors, Antigen, B-Cell immunology, Young Adult, B-Lymphocyte Subsets immunology, PTEN Phosphohydrolase deficiency, Purpura, Thrombocytopenic, Idiopathic immunology
- Abstract
Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP., (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Published
- 2018
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