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

• Published in: International journal of hematology 2021-11, Vol.114 (5), p.580-590
• Main Authors: Hayashi, Tetsuya, Nakamae, Hirohisa, Takeda, Shinichi, Nakashima, Yasuhiro, Koh, Hideo, Nishimoto, Mitsutaka, Okamura, Hiroshi, Nanno, Satoru, Makuuchi, Yosuke, Kuno, Masatomo, Nakamae, Mika, Hirose, Asao, Hino, Masayuki
• Format: Article
• Language: English
• Subjects: Antibodies; Autoimmunity; BLyS protein; CD19 antigen; Cytokines; Germinal centers; Globulins; Hematology; Homeostasis; Idiopathic thrombocytopenic purpura; Immunoglobulins; Interferon; Lymphocytes; Lymphocytes B; Medicine; Medicine & Public Health; Oncology; Original Article; Patients; Thrombocytopenia; α-Interferon
• ISSN: 0925-5710; 1865-3774
• DOI: 10.1007/s12185-021-03192-w

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 + CD24 high CD38 high 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.