Humoral markers of active Epstein-Barr virus infection associate with anti-extractable nuclear antigen autoantibodies and plasma galectin-3 binding protein in systemic lupus erythematosus

Lupus. 2016 Dec;25(14):1567-1576. doi: 10.1177/0961203316644334. Epub 2016 Apr 15.


We investigated if signs of active Epstein-Barr virus and cytomegalovirus infections associate with certain autoantibodies and a marker of type I interferon activity in patients with systemic lupus erythematosus. IgM and IgG plasma levels against Epstein-Barr virus early antigen diffuse and cytomegalovirus pp52 were applied as humoral markers of ongoing/recently active Epstein-Barr virus and cytomegalovirus infections, respectively. Plasma galectin-3 binding protein served as a surrogate marker of type I interferon activity. The measurements were conducted in 57 systemic lupus erythematosus patients and 29 healthy controls using ELISAs. Regression analyses and univariate comparisons were performed for associative evaluation between virus serology, plasma galectin-3 binding protein and autoantibodies, along with other clinical and demographic parameters. Plasma galectin-3 binding protein concentrations were significantly higher in systemic lupus erythematosus patients (P = 0.009) and associated positively with Epstein-Barr virus early antigen diffuse-directed antibodies and the presence of autoantibodies against extractable nuclear antigens in adjusted linear regressions (B = 2.02 and 2.02, P = 0.02 and P = 0.002, respectively). Furthermore, systemic lupus erythematosus patients with anti-extractable nuclear antigens had significantly higher antibody levels against Epstein-Barr virus early antigen diffuse (P = 0.02). Our study supports a link between active Epstein-Barr virus infections, positivity for anti-extractable nuclear antigens and increased plasma galectin-3 binding protein concentrations/type I interferon activity in systemic lupus erythematosus patients.

Keywords: Epstein–Barr virus; SLE; antibodies; cytomegalovirus; early antigens; interferon.

MeSH terms

  • Adult
  • Antibodies, Antinuclear / blood*
  • Antibodies, Viral / blood
  • Antigens, Neoplasm / blood*
  • Antigens, Nuclear / immunology
  • Antigens, Viral / immunology
  • Biomarkers / blood
  • Biomarkers, Tumor / blood*
  • Carrier Proteins / blood*
  • Case-Control Studies
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / blood*
  • Denmark
  • Epstein-Barr Virus Infections / blood*
  • Female
  • Glycoproteins / blood*
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin M / blood
  • Interferon Type I / blood
  • Linear Models
  • Logistic Models
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / immunology*
  • Male


  • Antibodies, Antinuclear
  • Antibodies, Viral
  • Antigens, Neoplasm
  • Antigens, Nuclear
  • Antigens, Viral
  • Biomarkers
  • Biomarkers, Tumor
  • Carrier Proteins
  • Epstein-Barr virus early antigen
  • Glycoproteins
  • Immunoglobulin G
  • Immunoglobulin M
  • Interferon Type I
  • LGALS3BP protein, human