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. 2021 Nov;114(5):580-590. doi: 10.1007/s12185-021-03192-w. Epub 2021 Jul 26.


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.

Keywords: B cell-activating factor belonging to the tumor necrosis factor family; Immune thrombocytopenia; Immunophenotyping; Pre-germinal center B cells; Regulatory B cells.

MeSH terms

  • ADP-ribosyl Cyclase 1 / metabolism
  • Antigens, CD19 / metabolism
  • Autoimmunity*
  • B-Lymphocyte Subsets / immunology
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes, Regulatory / immunology*
  • B-Lymphocytes, Regulatory / metabolism*
  • Biomarkers
  • CD24 Antigen / metabolism
  • Cross-Sectional Studies
  • Cytokines / blood
  • Disease Susceptibility
  • Germinal Center / immunology*
  • Germinal Center / metabolism
  • Humans
  • Immunophenotyping
  • Lymphocyte Count*
  • Precursor Cells, B-Lymphoid / immunology*
  • Precursor Cells, B-Lymphoid / metabolism*
  • Prognosis
  • Purpura, Thrombocytopenic, Idiopathic / blood
  • Purpura, Thrombocytopenic, Idiopathic / immunology*
  • Purpura, Thrombocytopenic, Idiopathic / mortality*
  • Purpura, Thrombocytopenic, Idiopathic / therapy
  • Treatment Outcome


  • Antigens, CD19
  • Biomarkers
  • CD24 Antigen
  • CD24 protein, human
  • Cytokines
  • ADP-ribosyl Cyclase 1