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01-08-2019 | Thrombocytopenia | Original Article

The abnormal function of CD39⁺ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia

Authors: Yumeng Lu, Luya Cheng, Feng Li, Lili Ji, Xia Shao, Boting Wu, Yanxia Zhan, Chanjuan Liu, Zhihui Min, Yang Ke, Lihua Sun, Hao Chen, Yunfeng Cheng

Published in: Annals of Hematology | Issue 8/2019

Abstract

Primary immune thrombocytopenia is an autoimmune disease, characterized with decreased platelet and increased risk of bleeding. Recent studies have shown the reduction and dysfunction of regulatory T (Treg) cells in ITP patients. CD39 is highly expressed on the surface of Treg cells. It degrades ATP to AMP and CD73 dephosphorylates AMP into adenosine. Then adenosine binds with adenosine receptor and suppresses immune response by activating Treg cells and inhibiting the release of inflammatory cytokines from effector T (Teff) cells. Adenosine receptor has several subtypes and adenosine A2A receptor (A2AR) plays a crucial role especially within lymphocytes. The CD39⁺ Treg cells and the expression of A2AR showed abnormality in some autoimmune disease. But knowledge of CD39⁺ Treg cells and A2AR which are crucial in the adenosine immunosuppressive pathway is still limited in ITP. Thirty-one adult patients with newly diagnosed ITP were enrolled in this study. CD39 and A2AR expression was measured by flow cytometry and RT-PCR. The function of CD39 was reflected by the change of ATP concentration detected by CellTiter-Glo Luminescent Cell Viability Assay. CD39 expression within CD4⁺CD25⁺ Treg cells in ITP patients was decreased compared to normal controls. After high-dose dexamethasone therapy, response (R) group showed increased CD39 expression within Treg cells while non-response (NR) group did not show any difference in contrast to those before treatment. The expression of A2AR in CD4⁺CD25⁻ Teff and CD4⁺CD25⁺ Treg cells was both lower in ITP patients than that of normal controls. After therapy, CD4⁺CD25⁻ Teff cells had higher A2AR expression while CD4⁺CD25⁺ Treg cells did not show any difference in comparison to that before treatment. The enzymatic activity of CD39 was damaged in ITP patients and improved after high-dose dexamethasone therapy. In ITP, there was not only numerical decrease but also impaired enzymatic activity in CD39⁺ Treg cells. After high-dose dexamethasone treatment, these two defects could be reversed. Our results also suggested that ITP patients had reduced A2AR expression in both CD4⁺CD25⁺ Treg cells and CD4⁺CD25⁻ Teff cells. CD4⁺CD25⁻ Teff cells had increased A2AR expression after treatment.

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Title: The abnormal function of CD39+ regulatory T cells could be corrected by high-dose dexamethasone in patients with primary immune thrombocytopenia
Authors: Yumeng Lu
Luya Cheng
Feng Li
Lili Ji
Xia Shao
Boting Wu
Yanxia Zhan
Chanjuan Liu
Zhihui Min
Yang Ke
Lihua Sun
Hao Chen
Yunfeng Cheng
Publication date: 01-08-2019
Publisher: Springer Berlin Heidelberg
Keywords: Thrombocytopenia
Dexamethasone
Published in: Annals of Hematology / Issue 8/2019
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-019-03716-9

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