Discovery of new serum biomarker panels for systemic lupus erythematosus diagnosis

Rheumatology (Oxford). 2020 Jun 1;59(6):1416-1425. doi: 10.1093/rheumatology/kez634.

Abstract

Objective: Clinical diagnosis of SLE is currently challenging due to its heterogeneity. Many autoantibodies are associated with SLE and are considered potential diagnostic markers, but systematic screening and validation of such autoantibodies is lacking. This study aimed to systematically discover new autoantibodies that may be good biomarkers for use in SLE diagnosis.

Methods: Sera from 15 SLE patients and 5 healthy volunteers were analysed using human proteome microarrays to identify candidate SLE-related autoantibodies. The results were validated by screening of sera from 107 SLE patients, 94 healthy volunteers and 60 disease controls using focussed arrays comprised of autoantigens corresponding to the identified candidate antibodies. Logistic regression was used to derive and validate autoantibody panels that can discriminate SLE disease. Extensive ELISA screening of sera from 294 SLE patients and 461 controls was performed to validate one of the newly discovered autoantibodies.

Results: A total of 31, 11 and 18 autoantibodies were identified to be expressed at significantly higher levels in the SLE group than in the healthy volunteers, disease controls and healthy volunteers plus disease control groups, respectively, with 25, 7 and 13 of these differentially expressed autoantibodies being previously unreported. Diagnostic panels comprising anti-RPLP2, anti-SNRPC and anti-PARP1, and anti-RPLP2, anti-PARP1, anti-MAK16 and anti- RPL7A were selected. Performance of the newly discovered anti-MAK16 autoantibody was confirmed by ELISA. Some associations were seen with clinical characteristics of SLE patients, such as disease activity with the level of anti-PARP1 and rash with the level of anti-RPLP2, anti-MAK16 and anti- RPL7A.

Conclusion: The combined autoantibody panels identified here show promise for the diagnosis of SLE and for differential diagnosis of other major rheumatic immune diseases.

Keywords: autoantibodies; biomarker; diagnosis; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Case-Control Studies
  • Diagnosis, Differential
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Logistic Models
  • Lupus Erythematosus, Systemic / diagnosis*
  • Male
  • Middle Aged
  • Phosphoproteins / immunology
  • Poly (ADP-Ribose) Polymerase-1 / immunology
  • Protein Array Analysis / methods*
  • Protein-Serine-Threonine Kinases / immunology
  • Proteome
  • Reproducibility of Results
  • Ribonucleoproteins, Small Nuclear / immunology
  • Ribosomal Proteins / immunology

Substances

  • Autoantibodies
  • Biomarkers
  • Phosphoproteins
  • Proteome
  • RPL7A protein, human
  • Ribonucleoproteins, Small Nuclear
  • Ribosomal Proteins
  • SNRPC protein, human
  • phosphoprotein P2, ribosomal
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Protein-Serine-Threonine Kinases
  • MAK protein, human