IL-21 dependent Granzyme B production of B-cells is decreased in patients with lupus nephritis

Clin Immunol. 2018 Mar:188:45-51. doi: 10.1016/j.clim.2017.12.005. Epub 2017 Dec 21.

Abstract

Objectives: B-cells play a crucial role in the pathogenesis of lupus nephritis. Recently, a separate subset has been discovered characterized by expression of Granzyme B. The aim of this study is to investigate this subset in patients with systemic lupus erythematosus (SLE).

Methods: Isolated PBMCs of SLE-patients (n=30) and healthy controls (n=21) were in vitro stimulated with CPG, IgG+IgM and IL-21. Patients were sub-grouped in patients with and without biopsy proven lupus nephritis. B-cells were analyzed for intracellular Granzyme B expression by flow cytometry.

Results: The strongest stimulus for Granzyme B secretion of B-cells was IgG+IgM in presence of IL-21. SLE-patients had a significant decreased percentage of Granzyme B+ B-cells in particular SLE-patients with active disease and with lupus nephritis.

Conclusions: The frequency of GrB+ producing B-cells is reduced in SLE patients. This may contribute to an imbalanced B-cell regulation towards effector B-cells which might promote the development of lupus nephritis.

Keywords: Granzyme B; IL-21; Lupus nephritis; SLE.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD19 / immunology
  • Antigens, CD19 / metabolism
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Cells, Cultured
  • Female
  • Granzymes / immunology*
  • Granzymes / metabolism
  • Humans
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Immunoglobulin M / immunology
  • Immunoglobulin M / pharmacology
  • Interleukins / immunology
  • Interleukins / pharmacology*
  • Lupus Erythematosus, Systemic / immunology*
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Nephritis / immunology*
  • Lupus Nephritis / metabolism
  • Male
  • Middle Aged
  • Receptors, Interleukin-21 / immunology
  • Receptors, Interleukin-21 / metabolism

Substances

  • Antigens, CD19
  • Immunoglobulin G
  • Immunoglobulin M
  • Interleukins
  • Receptors, Interleukin-21
  • Granzymes
  • interleukin-21