Page 124 - 2021_03-Haematologica-web

Ferrata Storti Foundation
Haematologica 2021 Volume 106(3):770-781
Platelet Biology and its Disorders
Human leukocyte antigen-G upregulates immunoglobulin-like transcripts and corrects dysfunction of immune cells in immune thrombocytopenia
Xin Li,1* Zi Sheng,1* Yuanxin Sun,2 Yuanjian Wang,3 Miao Xu,1 Zhiyue Zhang,4 Hui Li,4 Linlin Shao,1 Yanqi Zhang,2 Jinming Yu,5 Chunhong Ma,6
Chengjiang Gao,6 Ming Hou,2 Heyu Ni,7,8,9,10 Jun Peng,2 Ji Ma5,11 and Qi Feng1
1
Department of Hematology, Qilu Hospital, Shandong University, Jinan, China;
2
Department of Medical Oncology, Shandong Provincial Institute of Cancer Prevention and
Treatment, Shandong Cancer Hospital, Shandong University, Jinan, China; 3West China School of Medicine, Sichuan University, Chengdu, China; 4Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, China; 5Department of Medical Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China; 6Department of Immunology, Shandong University School of Medicine, Jinan, China; 7Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada; 8Toronto Platelet Immunobiology Group, University of Toronto, Toronto, Ontario, Canada; 9Department of Laboratory Medicine, Keenan Research Center for Biomedical Science, St. Michael's Hospital, Toronto, Ontario, Canada; 10Canadian Blood Services Center for Innovation, Toronto, Ontario, Canada and 11Department of Medical Oncology, Tianjin Medical University, Tianjin, China
*XL and ZS contributed equally as co-first authors.
ABSTRACT
Human leukocyte antigen-G (HLA-G) is a non-classical major histo- compatibility complex class I antigen with potent immune-inhibito- ry function. HLA-G benefit patients in allotransplantation and autoimmune diseases by interacting with its receptors, immunoglobulin- like transcripts. Here we observed significantly less HLA-G in plasma from immune thrombocytopenia (ITP) patients positive for anti-platelet autoan- tibodies compared with autoantibodies-negative patients or healthy con- trols, while we found that HLA-G is positively correlated with platelet counts in both patients and healthy controls. We also found less membrane- bound HLA-G and immunoglobulin-like transcripts on CD4+ and CD14+ cells in patients. Recombinant HLA-G upregulated immunoglobulin-like transcript 2 expression on CD4+ and immunoglobulin-like transcript 4 on CD14+ cells. HLA-G upregulated IL-4 and IL-10, and downregulated tumor necrosis factor-a, IL-12 and IL-17 secreted by patient peripheral blood mononuclear cells, suggesting a stimulation of Th2 differentiation and downregulation of Th1 and Th17 immune response. HLA-G-modulated dendritic cells from ITP patients showed decreased expression of CD80 and CD86, and suppressed CD4+ T-cell proliferation compared to unmodulated cells. Moreover, HLA-G-modulated cells from patients induced less platelet apoptosis. HLA-G administration also significantly alleviated thrombocy- topenia in a murine model of ITP. In conclusion, our data demonstrated that impaired expression of HLA-G and immunoglobulin-like transcripts is involved in the pathogenesis of ITP; recombinant HLA-G can correct this abnormality via upregulation of immunoglobulin-like transcripts, indicating that HLA-G can be a diagnostic marker and a therapeutic option for ITP.
Introduction
Immune thrombocytopenia (ITP) is a common autoimmune bleeding disorder with decreased platelet counts.1-4 The therapeutic regimens for ITP patients, inclu- ding glucocorticosteroids, intravenous immunoglobulin, thrombopoietin receptor agonists, rituximab and other immunoregulatory drugs, are not always effective,
Correspondence:
QI FENG
fengqi0313@163.com
JI MA
phd_jima@163.com
Received: August, 9, 2018. Accepted: February 12, 2020. Pre-published: February 20, 2020.
https://doi.org/10.3324/haematol.2018.204040
©2021 Ferrata Storti Foundation
Material published in Haematologica is covered by copyright. All rights are reserved to the Ferrata Storti Foundation. Use of published material is allowed under the following terms and conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode. Copies of published material are allowed for personal or inter- nal use. Sharing published material for non-commercial pur- poses is subject to the following conditions: https://creativecommons.org/licenses/by-nc/4.0/legalcode, sect. 3. Reproducing and sharing published material for com- mercial purposes is not allowed without permission in writing from the publisher.
770
haematologica | 2021; 106(3)
ARTICLE