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Increasing numbers of CD19 + CD24highCD38high regulatory B cells and pre-germinal center B cells reflect activated autoimmunity and predict future treatment response in patients with untreated immune thrombocytopenia

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Abstract

The pathophysiology of immune thrombocytopenia (ITP) is poorly understood, particularly aspects regarding abnormal homeostasis and dysregulation of B cells. In this study, we analyzed peripheral lymphocyte subsets in patients with untreated ITP and healthy controls, and examined correlations between cell percentages/counts and titers of serum cytokines and antibodies. We also compared ITP patients who later required second-line therapies and those who did not. The percentages of CD19 + CD24highCD38high regulatory B cells, pre-germinal center (GC) B cells, and plasmablast-like B cells were significantly higher in ITP patients than in healthy controls. Absolute counts of regulatory B cells and pre-GC B cells were significantly higher in those who needed second-line therapies. In addition, serum B cell-activating factor belonging to the tumor necrosis factor family (BAFF) levels and platelet-associated immune globulin G antibody titers correlated positively with regulatory B cell, pre-GC B cell, and auto-reactive B cell counts. Serum interferon-α (IFN-α) levels were elevated in four ITP patients with high auto-reactive B cell counts. These results indicate that increases in regulatory B cells and pre-GC B cells may reflect activated autoimmunity induced by BAFF and/or IFN-α. Consequently, evaluation of B cell subsets in untreated ITP patients may predict treatment response.

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Acknowledgements

The authors thank S. Kikuchi for patient enrollment, N. Osaki for technical assistance, and S. Ishikawa for secretarial assistance.

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Authors and Affiliations

  1. Hematology, Graduate School of Medicine, Osaka City University, 1-4-3 Asahi-machi, Abeno-ku, Osaka, 545-8585, Japan

    Tetsuya Hayashi, Hirohisa Nakamae, Yasuhiro Nakashima, Hideo Koh, Mitsutaka Nishimoto, Hiroshi Okamura, Satoru Nanno, Yosuke Makuuchi, Masatomo Kuno, Mika Nakamae, Asao Hirose & Masayuki Hino

  2. Department of Clinical Laboratory, Osaka City University Hospital, Osaka, Japan

    Shinichi Takeda & Mika Nakamae

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  1. Tetsuya Hayashi
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Correspondence to Hirohisa Nakamae.

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Conflicts of interest

Dr. Hayashi reports honoraria from MSD K.K. and Kyowa Kirin Co., Ltd. (none of which are related to the submitted work). Dr. Hirohisa Nakamae reports grants from Novartis Pharma K.K., honoraria from Takeda Pharmaceutical Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K., Celgene Corporation, Kyowa Kirin Co., Ltd., and Nippon Shinyaku Co., Ltd.; and an advisory board fee from Chugai Pharmaceutical Co., Ltd., Novartis Pharma K.K., and Pfizer Japan Inc. (none of which are related to the submitted work). Dr. Nakashima reports grants from Eisai Co., Ltd., Celgene Corporation, and Novartis Pharma K.K., honoraria from Eisai Co., Ltd., Pfizer Japan Inc., Novartis Pharma K.K., and Kyowa Kirin Co., Ltd., and an advisory fee from Novartis Pharma K.K. (none of which are related to the submitted work). Dr. Koh reports grants from Chugai Pharmaceutical Co., Ltd., Asahi Kasei Pharma Corporation, and Takeda Pharmaceutical Co., Ltd., honoraria from MSD K.K., Takeda Pharmaceutical Co., Ltd., and Sumitomo Dainippon Pharma Co., Ltd., an advisory board fee from Takeda Pharmaceutical Co., Ltd., and a consulting fee from MSD K.K. (none of which are related to the submitted work). Dr. Nishimoto reports honoraria from Kyowa Kirin Co., Ltd. (none of which are related to the submitted work). Dr. Okamura reports honoraria from Eisai Co., Ltd. and Nippon Shinyaku Co., Ltd. (none of which are related to the submitted work). Dr. Nanno reports honoraria from Eisai Co., Ltd. (none of which are related to the submitted work). Dr. Mika Nakamae reports honoraria from Novartis Pharma K.K. (none of which are related to the submitted work). Dr. Hino reports grants from Pfizer Japan Inc., MSD K.K., and Novartis Pharma K.K., honoraria from MSD K.K., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Celgene Corporation, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Novartis Pharma K.K., and Pfizer Japan Inc., an advisory board fee from Pfizer Japan Inc., and a consulting fee from Kyowa Kirin Co., Ltd. (none of which are related to the submitted work). All the authors (our institution) report grants from MSD K.K., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Takeda Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co., Ltd., Teijin Pharma, Ltd., Pfizer Japan Inc., and Sumitomo Dainippon Pharma Co., Ltd. (none of which are related to the submitted work).

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Hayashi, T., Nakamae, H., Takeda, S. et al. Increasing numbers of CD19 + CD24highCD38high regulatory B cells and pre-germinal center B cells reflect activated autoimmunity and predict future treatment response in patients with untreated immune thrombocytopenia. Int J Hematol 114, 580–590 (2021). https://doi.org/10.1007/s12185-021-03192-w

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