Early systemic sclerosis: serum profiling of factors involved in endothelial, T-cell, and fibroblast interplay is marked by elevated interleukin-33 levels

J Clin Immunol. 2014 Aug;34(6):663-8. doi: 10.1007/s10875-014-0037-0. Epub 2014 Apr 24.

Abstract

Purpose: To assess the serum profile of factors involved in endothelial, T-cell, and fibroblast interplay in patients with Raynaud's phenomenon (RP) associated with nailfold vodeocapillaroscopy (NVC) scleroderma findings and/or systemic sclerosis (SSc) marker autoantibodies, recently labeled as early SSc patients.

Methods: Serum levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), CCL2, CXCL8, IL-13, IL-33, and transforming growth factor-β (TGF-β) were measured in 24 early SSc patients, 48 definite SSc patients, and 24 osteoarthritis/fibromyalgia controls by multiplex suspension immunoassay. All SSc patients were investigated for the presence/absence of preclinical and clinical organ involvement, SSc marker autoantibodies, and NVC abnormalities.

Results: Serum sICAM-1, CCL2, CXCL8, and IL-13 were increased in all SSc patients as compared to controls, and paralleled the severity of the disease subset (early SSc < limited cutaneous SSc < diffuse cutaneous SSc; p < 0.0001). Surprisingly, IL-33 was significantly higher in early SSc patients as compared to both controls (p < 0.01) and definite SSc patients (p < 0.05). In early SSc there were no differences in the investigated markers according to the functional and serological features assessed.

Conclusions: Our study suggests that an endothelial, T-cell and fibroblast activation can be present in patients with early SSc and it is associated with a distinct profile of circulating factors involved in the cross-talk of these cells. The marked increase of IL-33 in early SSc patients suggests new routes of investigation of cell-cell dynamics in target tissues predating overt disease manifestations, thus opening to new therapeutic approaches.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Antibodies, Antinuclear / metabolism
  • Biomarkers / metabolism*
  • Capillaries / pathology
  • Cell Communication
  • Cells, Cultured
  • Chemokine CCL2 / blood
  • Disease Progression
  • Endothelial Cells / immunology*
  • Female
  • Fibroblasts / immunology*
  • Humans
  • Intercellular Adhesion Molecule-1 / blood
  • Interleukin-13 / blood
  • Interleukin-33
  • Interleukin-8 / blood
  • Interleukins / metabolism*
  • Male
  • Mice
  • Microscopic Angioscopy
  • Middle Aged
  • Raynaud Disease / diagnosis*
  • Raynaud Disease / immunology
  • Scleroderma, Systemic / diagnosis*
  • Scleroderma, Systemic / immunology
  • T-Lymphocytes / immunology*

Substances

  • Antibodies, Antinuclear
  • Biomarkers
  • Chemokine CCL2
  • IL33 protein, human
  • Interleukin-13
  • Interleukin-33
  • Interleukin-8
  • Interleukins
  • Intercellular Adhesion Molecule-1