Sera from anti-Jo-1-positive patients with polymyositis and interstitial lung disease induce expression of intercellular adhesion molecule 1 in human lung endothelial cells

Arthritis Rheum. 2009 Aug;60(8):2524-30. doi: 10.1002/art.24683.

Abstract

Objective: To investigate whether sera or purified IgG from patients with polymyositis (PM) and patients with dermatomyositis (DM), with or without interstitial lung disease (ILD), can activate endothelial cells (ECs).

Methods: Patients' sera were selected based on the presence or absence of anti-Jo-1, anti-SSA, or anti-U1 small nuclear RNP autoantibodies. The presence of autoantibodies was determined by line blot assays. Cultured human microvascular ECs derived from lung tissue (HMVEC-L) were incubated with sera or purified IgG from 22 patients with PM, 7 patients with DM, and 10 healthy individuals as controls. Assessment of intercellular adhesion molecule 1 (ICAM-1) expression was conducted by immunofluorescence (n=22) and by cell-based enzyme-linked immunosorbent assay (ELISA) (n=20). Serum levels of soluble ICAM-1 (sICAM-1) were determined by ELISA.

Results: Sera from PM patients with ILD who were positive for anti-Jo-1 autoantibodies had a significantly stronger effect on the expression of ICAM-1 by HMVEC-L in comparison with sera from healthy controls and patients with other autoantibodies. Purified IgG did not induce ICAM-1 expression. Higher serum levels of sICAM-1 were found in patients with myositis compared with healthy controls.

Conclusion: EC activation with ICAM-1 expression could contribute to the multiorgan involvement, including the development of myositis and ILD, in patients carrying anti-Jo-1 autoantibodies. The EC-activating factors are not the autoantibodies themselves, but might be systemic factors associated with these autoantibodies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antinuclear / blood*
  • Antibodies, Antinuclear / pharmacology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects
  • Endothelium, Vascular / metabolism*
  • Female
  • Histidine-tRNA Ligase / immunology
  • Humans
  • Immune Sera / immunology
  • Immune Sera / pharmacology
  • Immunoglobulin G / pharmacology
  • Intercellular Adhesion Molecule-1 / blood
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lung / blood supply
  • Lung Diseases, Interstitial / blood*
  • Lung Diseases, Interstitial / immunology
  • Male
  • Microvessels / cytology
  • Middle Aged
  • Polymyositis / blood*
  • Polymyositis / immunology
  • Young Adult

Substances

  • Antibodies, Antinuclear
  • Immune Sera
  • Immunoglobulin G
  • Jo-1 antibody
  • Intercellular Adhesion Molecule-1
  • Histidine-tRNA Ligase