Increased lipid and protein oxidation and lowered anti-oxidant defenses in systemic lupus erythematosus are associated with severity of illness, autoimmunity, increased adhesion molecules, and Th1 and Th17 immune shift

Immunol Res. 2018 Feb;66(1):158-171. doi: 10.1007/s12026-017-8960-9.

Abstract

This study investigated nitro-oxidative stress in patients with systemic lupus erythematosus (SLE) in association with disease activity, immune-inflammatory biomarkers, and adhesion molecules. Two-hundred-four patients with SLE and 256 healthy volunteers were enrolled in this case-control study, which measured nitro-oxidative stress biomarkers, including lipid peroxides (LOOH), advanced oxidation protein products (AOPPs), nitric oxide metabolites (NOx), sulfhydryl (-SH) groups, products of deoxyribonucleic acid (DNA)/ribonucleic acid (RNA) oxidative degradation, and total radical-trapping anti-oxidant parameter (TRAP). Also measured were anti-nuclear antibodies (ANAs), antibodies against double-stranded DNA (dsDNA), plasma levels of diverse cytokines, C-reactive protein, and adhesion molecules. LOOH (p < 0.001) and AOPP (p < 0.001) were significantly higher, while TRAP was significantly lower (p < 0.001) in SLE patients than in controls. AOPP and LOOH were significantly and positively associated with SLE disease activity index (SLEDAI) scores, anti-nuclear antibodies, and antibodies against double-stranded DNA (anti-dsDNA) levels, while TRAP was significantly and inversely correlated with SLEDAI, ANA, and dsDNA antibody levels. There were significant positive associations between AOPP and LOOH and immune-inflammatory markers, indicating T helper (Th)-17 and Th1 bias and Th1 + Th17/Th2 ratio (p = 0.002 and p = 0.001, respectively). AOPP and LOOH (positively) and TRAP (inversely) were associated with adhesion molecule expression. A model predicting SLE was computed showing that, using LOOH, AOPP, NOx, adhesion molecules, and body mass index, 94.2% of the patients were correctly classified with a specificity of 91.5%. Increased nitro-oxidative stress takes part in the (auto)immune pathophysiology of SLE and modulates severity of illness and adhesion molecule expression.

Keywords: Adhesion molecules; Anti-oxidant; Cytokines; Reactive oxygen and nitrogen species; Systemic lupus erythematosus.

MeSH terms

  • Adult
  • Advanced Oxidation Protein Products / metabolism
  • Antibodies, Antinuclear / blood
  • Biomarkers / metabolism*
  • Cell Adhesion Molecules / metabolism
  • Female
  • Humans
  • Inflammation / metabolism*
  • Lipid Peroxides / metabolism
  • Lupus Erythematosus, Systemic / immunology
  • Lupus Erythematosus, Systemic / metabolism*
  • Male
  • Middle Aged
  • Nitric Oxide / metabolism
  • Nitrosative Stress
  • Oxidative Stress
  • Th1 Cells / immunology*
  • Th17 Cells / immunology*

Substances

  • Advanced Oxidation Protein Products
  • Antibodies, Antinuclear
  • Biomarkers
  • Cell Adhesion Molecules
  • Lipid Peroxides
  • Nitric Oxide