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Decreased RAGE expression in peripheral blood mononuclear cells of patients with rheumatoid arthritis

S Drinda1, S Franke, T Eidner

  • 1Department of Internal Medicine III, Division of Gastroenterology, Friedrich-Schiller-University, D-07740 Jena, Germany.

Clinical and Experimental Rheumatology
|July 17, 2009
PubMed
Abstract

Insights

Rheumatoid arthritis (RA) patients show reduced expression of receptor for advanced glycation end products (RAGE) variants in blood cells, potentially impacting inflammatory responses and disease progression.

Area of Science:

  • Immunology
  • Molecular Biology
  • Pathophysiology

Background:

  • The receptor for advanced glycation end products (RAGE) and its ligands are implicated in chronic inflammatory diseases like rheumatoid arthritis (RA).
  • Peripheral blood mononuclear cells (PBMCs) play a role in the pathogenesis of these conditions.

Purpose of the Study:

  • To investigate the expression levels of RAGE variants (endogenous secretory RAGE - esRAGE, N-truncated RAGE - NtRAGE, and complete RAGE - cRAGE) in PBMCs of RA patients compared to healthy controls and Crohn's disease (CD) patients.

Main Methods:

  • Real-time PCR was used to measure mRNA expression of cRAGE, esRAGE, and NtRAGE in PBMCs.
  • Western blot analysis determined RAGE protein expression.
  • ELISA measured plasma levels of esRAGE.

Main Results:

  • RA patients exhibited significantly decreased mRNA expression of cRAGE (46%), esRAGE (54%), and NtRAGE (52%) in PBMCs compared to controls.
  • CD patients showed a lower degree of down-regulation in RAGE mRNA expression.
  • RA PBMCs displayed significantly reduced full-length RAGE protein expression (53%) and lower plasma esRAGE concentrations (70%).

Conclusions:

  • Down-regulation of RAGE isoforms in RA PBMCs may impair intracellular signaling pathways.
  • Reduced circulating esRAGE levels in RA patients could diminish their capacity to neutralize inflammatory ligands.

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