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Abnormalities of the bone marrow immune microenvironment in patients with immune thrombocytopenia

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Abstract

Immune thrombocytopenia (ITP) is an acquired autoimmune disease. Although antiplatelet antibodies are considered as the primary immunologic defect in these patients, dysfunctional cellular immunity is also important in the pathophysiology of ITP. Peripheral T cell abnormalities have been demonstrated in patients with ITP; however, whether the impaired bone marrow (BM) microenvironment, specifically the BM immune microenvironment, is involved in the pathogenesis of ITP remains unknown. In this study, the compartments of the BM immune microenvironment and BM vascular microenvironment were analyzed in 26 untreated patients with ITP and 26 healthy donors (HD). Subsets of T cells in the BM immune microenvironment, including Th1, Th2, Tc1, Tc2, Th17, and Treg cells, were analyzed via flow cytometry. BM endothelial cells and perivascular cells, which are key elements of the vascular microenvironment, were analyzed via flow cytometry as well as hematoxylin-eosin (H&E) and immunohistochemical (IHC) staining in situ. Elements of the BM vascular microenvironment were found to be normal in patients with ITP, but abnormal characteristics of the BM immune microenvironment, including excessive polarization in Th1, Tc1, and Th17 cells and a remarkable decrease in Treg cells, were observed in patients with ITP. Therefore, a deregulated T cell response in the BM microenvironment might play an important role in the pathogenesis of ITP.

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Authors and Affiliations

  1. Peking University People’s Hospital, Peking University Institute of Hematology, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, Collaborative Innovation Center of Hematology, Peking University, Beijing, 100044, China

    Yang Song, Yu-Tong Wang, Xiao-Jun Huang & Yuan Kong

  2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China

    Yang Song & Xiao-Jun Huang

Authors
  1. Yang Song
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  2. Yu-Tong Wang
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  3. Xiao-Jun Huang
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  4. Yuan Kong
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Corresponding author

Correspondence to Yuan Kong.

Ethics declarations

Compliance with ethical standards, all procedures were in accordance with the ethical standards of the responsible committee on human experimentation and with the Helsinki Declaration of 1975, as revised in 2008.

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The authors declare that they have no conflict of interest.

Funding

This work was supported by the National Natural Science Foundation of China (grant nos. 81570127&81370638&81530046&81230013), Milstein Medical Asian American Partnership (MMAAP) Foundation, the Beijing Municipal Science and Technology Program (grant nos.Z151100004015164&Z151100001615020& Z141100000214011), and the Science and Technology Project of Guangdong Province of China.

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Song, Y., Wang, YT., Huang, XJ. et al. Abnormalities of the bone marrow immune microenvironment in patients with immune thrombocytopenia. Ann Hematol 95, 959–965 (2016). https://doi.org/10.1007/s00277-016-2641-y

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  • DOI: https://doi.org/10.1007/s00277-016-2641-y

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