Rituximab modulates IL-17 expression in the salivary glands of patients with primary Sjögren's syndrome

Rheumatology (Oxford). 2014 Jul;53(7):1313-20. doi: 10.1093/rheumatology/keu004. Epub 2014 Mar 6.

Abstract

Objective: The aim of this study was to evaluate the role of rituximab (RTX) in modulating the expression of the IL-17/IL-23 pathway in the salivary glands (SGs) of patients with primary SS (pSS).

Methods: Consecutive SG biopsies were obtained from 15 patients with pSS before and after 1 year of RTX therapy. The SG expression of IL-17, IL-23p19 and p-STAT3 was evaluated by immunohistochemistry at baseline and after RTX therapy. The role of mast cells in pSS patients in modulating the Th17 response and the immunologic effect of RTX on mast cells were also studied in in vitro experiments.

Results: IL-17 was overexpressed in the SGs of patients with pSS mainly by infiltrating T cells and mast cells. After RTX therapy, the SG expression of IL-17, but not of IL-23p19 and p-STAT3, was significantly reduced and was accompanied by the depletion of tissue mast cells. In in vitro experiments with heterologous peripheral lymphocytes RTX significantly induced the apoptosis of isolated mast cells. Finally, mast cells isolated from peripheral blood mononuclear cells of pSS patients in vitro significantly increased Th17 lymphocytes.

Conclusion: RTX acts on pSS patients by globally reducing the expression of IL-17 and specifically inducing a pronounced apoptotic depletion of mast cells.

Keywords: IL-17; IL-23; T lymphocytes; mast cells; p-STAT3; primary Sjögren’s syndrome; rituximab.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Murine-Derived / pharmacology*
  • Antibodies, Monoclonal, Murine-Derived / therapeutic use*
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Female
  • Humans
  • In Vitro Techniques
  • Interferons
  • Interleukin-17 / metabolism*
  • Interleukin-23 / metabolism
  • Interleukins / metabolism
  • Male
  • Mast Cells / drug effects
  • Mast Cells / pathology
  • Middle Aged
  • Rituximab
  • STAT3 Transcription Factor
  • Salivary Glands / drug effects*
  • Salivary Glands / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / metabolism
  • Th17 Cells / drug effects
  • Th17 Cells / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • IFNL1 protein, human
  • Interleukin-17
  • Interleukin-23
  • Interleukins
  • STAT3 Transcription Factor
  • Rituximab
  • Interferons