Autoantibody profiling reveals four protein candidate autoantigens associated with systemic lupus erythematosus

Lupus. 2018 Sep;27(10):1670-1678. doi: 10.1177/0961203318788153. Epub 2018 Jul 24.


Objectives In systemic lupus erythematosus (SLE) there are typically many autoantibodies. The disease heterogeneity could be better understood with discovery of phenotype-specific antigens targeted by autoantibodies. We here aimed to identify novel autoantigens potentially related to SLE disease and a major complication, atherosclerosis. Methods Antigen microarrays were used to profile IgG autoantibody reactivity against 77 protein fragments (20-140 amino acids (aa) long, median 89 aa) produced within the Human Protein Atlas project, in serum samples from SLE patients ( n = 107) and age- and sex-matched population-based controls ( n = 107). Common carotid intima-media thickness, plaque occurrence and echogenicity were determined by B-mode ultrasound. Results We determined significant differences between patients and controls in IgG reactivity against four proteins. In patients compared to controls, there was an increase of IgG reactivity against zinc finger protein 688 (ZNF688), early B cell factor 2 (EBF2), crystallin, alpha B (CRYAB) and tumor necrosis factor receptor superfamily member 13C (TNFRSF13C). Of these four antigens, only anti-ZNF688 was associated with carotid atherosclerosis (plaque occurrence) and vulnerable plaques in SLE. There was a weak association between anti-EBF2 and SLE disease activity but no significant associations were determined for other measured IgG reactivity. Conclusions In this discovery screening we here demonstrate new candidate autoantigens with differential reactivity (reflecting autoantibody levels) in SLE patients and in controls and in relation to atherosclerosis in SLE.

Keywords: Systemic lupus erythematosus; antibodies; atherosclerosis; autoantigen; protein array.

MeSH terms

  • Adult
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Autoantigens / immunology*
  • B-Cell Activation Factor Receptor / immunology
  • Basic Helix-Loop-Helix Transcription Factors / immunology
  • Biomarkers / blood
  • Carotid Artery Diseases / blood
  • Carotid Artery Diseases / diagnostic imaging
  • Carotid Artery Diseases / immunology
  • Carotid Artery, Common / diagnostic imaging
  • Carotid Intima-Media Thickness
  • Carrier Proteins / immunology
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / diagnosis
  • Lupus Erythematosus, Systemic / immunology*
  • Male
  • Middle Aged
  • Phenotype
  • Plaque, Atherosclerotic
  • Predictive Value of Tests
  • Prognosis
  • Protein Array Analysis*
  • alpha-Crystallin B Chain / immunology


  • Autoantibodies
  • Autoantigens
  • B-Cell Activation Factor Receptor
  • Basic Helix-Loop-Helix Transcription Factors
  • Biomarkers
  • CRYAB protein, human
  • Carrier Proteins
  • EBF2 protein, human
  • Immunoglobulin G
  • TNFRSF13C protein, human
  • ZNF688 protein, human
  • alpha-Crystallin B Chain