Increased numbers of circulating ICOS⁺ follicular helper T and CD38⁺ plasma cells in patients with newly diagnosed primary biliary cirrhosis

Dig Dis Sci. 2015 Feb;60(2):405-13. doi: 10.1007/s10620-014-3372-3. Epub 2014 Nov 18.

Abstract

Background: Aberrant activation of follicular helper T (TFH) and B cells is associated with the development of autoimmune diseases. However, little is known about the potential role of these cells in the development of primary biliary cirrhosis (PBC).

Aim: This study aimed at characterizing the numbers of different subsets of circulating Tfh and B cells as well as evaluating their potential association with the levels of immunoglobulins and autoantibodies in newly diagnosed PBC patients.

Methods: The numbers of circulating CD27(+), CD38(+), CD86(+) and CD95(+) B cells as well as inducible T cell costimulator (ICOS)(+) and programmed death-1 (PD-1)(+), IL-21(+) TFH cells were examined in 58 patients with newly diagnosed PBC and 30 matched healthy controls (HCs).

Results: The numbers of circulating CD38(+)CD19(+), CD86(+)CD19(+), and CD95(+)CD19(+) B cells; CD3(+)CD4(+)CXCR5(+)ICOS(+) and CD3(+)CD4(+)CXCR5(+)PD-1(+) Tfh cells; and the levels of serum IL-21 in the PBC patients were significantly greater, but the numbers of CD27(+)CD19(+) B cells were significantly less than those in the HCs (p < 0.05). The numbers of CD3(+)CD4(+)CXCR5(+)ICOS(+) Tfh cells were positively correlated with the numbers of CD38(+)CD19(+) and CD86(+)CD38(+)CD19(+) B cells and the levels of serum anti-mitochondrial antibodies against M2 antigen (AMA-M2), AMA and immunolgubin M (IgM) in the PBC patients. The levels of serum IL-21 were positively correlated with the levels of serum AMA-M2, AMA, IgG and IgM, but negatively with the numbers of CD27(+)CD19(+) B cells in the PBC patients.

Conclusions: Increased numbers of circulating ICOS(+) and IL-21(+) Tfh and CD38(+) plasma cells may be exhibited by patients with recent diagnoses of PBC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-ribosyl Cyclase 1 / blood*
  • Adult
  • Aged
  • Autoantibodies / blood
  • Autoimmunity
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Biomarkers / blood
  • CD4 Lymphocyte Count
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • Humans
  • Immunoglobulins / blood
  • Inducible T-Cell Co-Stimulator Protein / blood*
  • Interleukins / blood
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / diagnosis
  • Liver Cirrhosis, Biliary / immunology*
  • Male
  • Membrane Glycoproteins / blood*
  • Middle Aged
  • Plasma Cells / immunology*
  • Plasma Cells / metabolism
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / metabolism
  • Up-Regulation

Substances

  • Autoantibodies
  • Biomarkers
  • ICOS protein, human
  • Immunoglobulins
  • Inducible T-Cell Co-Stimulator Protein
  • Interleukins
  • Membrane Glycoproteins
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1
  • interleukin-21