Frequency of CD4+CXCR5+ TFH cells in patients with hepatitis b virus-associated membranous nephropathy

Int Immunopharmacol. 2014 Sep;22(1):98-106. doi: 10.1016/j.intimp.2014.06.024. Epub 2014 Jun 24.

Abstract

The frequency of different subsets of CD4(+)CXCR5(+) TFH cells and serum cytokine levels were analyzed in a total of 14 patients with newly diagnosed hepatitis B virus-associated membranous nephropathy (HBV-MN), 12 individuals with immune-tolerant HBV infection (HBV-IT) and 12 healthy controls (HC). Serum cytokine levels were measured before and 10-12 weeks after treatment. Significantly higher frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)ICOS(+) and CD4(+)CXCR5(+)PD-1(+) TFH cells, and higher serum levels of IL-17A, IFN-γ, IL-2, IL-10, IL-4 and IL-21 were detected in HBV-MN patients compared to the HC. The percentage of CD4(+)CXCR5(+) TFH cells and serum IL-21 level in HBV-MN patients were also higher than the HBV-IT. The percentage of CD4(+)CXCR5(+) TFH cell was negatively correlated with the value of eGFR, and the percentage of CD4(+)CXCR5(+)ICOS(+) TFH cells was positively correlated with the 24-h urinary protein concentration. Notably, the percentage of CD4(+)CXCR5(+)PD-1(+) TFH cells was positively correlated with serum IL-21 level and 24-h urinary protein concentration. Treatment with prednisone or/and immunosuppressive drugs significantly reduced the frequency of CD4(+)CXCR5(+), CD4(+)CXCR5(+)PD-1(+) TFH cells and serum IL-21 level, but increased IL-4 and IL-10 levels in the patients. CD4(+)CXCR5(+) TFH cells, especially CD4(+)CXCR5(+)PD-1(+) TFH cells may participate in the pathogenesis of HBV-MN.

Keywords: HBV-MN; IL-21; IL-4; TFH cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4 Antigens / metabolism
  • Cells, Cultured
  • Cytokines / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Glomerulonephritis, Membranous / drug therapy
  • Glomerulonephritis, Membranous / etiology
  • Glomerulonephritis, Membranous / immunology*
  • Hepatitis B / complications
  • Hepatitis B / drug therapy
  • Hepatitis B / immunology*
  • Hepatitis B virus / immunology*
  • Humans
  • Immune Tolerance
  • Immunophenotyping
  • Immunosuppressive Agents / administration & dosage
  • Inducible T-Cell Co-Stimulator Protein / metabolism
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Prednisone / administration & dosage
  • Programmed Cell Death 1 Receptor / metabolism
  • Receptors, CXCR5 / metabolism
  • T-Lymphocyte Subsets / drug effects
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / virology
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Helper-Inducer / virology
  • Young Adult

Substances

  • CD4 Antigens
  • Cytokines
  • ICOS protein, human
  • Immunosuppressive Agents
  • Inducible T-Cell Co-Stimulator Protein
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Receptors, CXCR5
  • Prednisone