Biomarkers of erosive arthritis in systemic lupus erythematosus: Application of machine learning models

PLoS One. 2018 Dec 4;13(12):e0207926. doi: 10.1371/journal.pone.0207926. eCollection 2018.

Abstract

Objective: Limited evidences are available on biomarkers to recognize Systemic Lupus erythematosus (SLE) patients at risk to develop erosive arthritis. Anti-citrullinated peptide antibodies (ACPA) have been widely investigated and identified in up to 50% of X-ray detected erosive arthritis; conversely, few studies evaluated anti-carbamylated proteins antibodies (anti-CarP). Here, we considered the application of machine learning models to identify relevant factors in the development of ultrasonography (US)-detected erosive damage in a large cohort of SLE patients with joint involvement.

Methods: We enrolled consecutive SLE patients with arthritis/arthralgia. All patients underwent joint (DAS28, STR) and laboratory assessment (detection of ACPA, anti-CarP, Rheumatoid Factor, SLE-related antibodies). The bone surfaces of metacarpophalangeal and proximal interphalangeal joints were assessed by US: the presence of erosions was registered with a dichotomous value (0/1), obtaining a total score (0-20). Concerning machine learning techniques, we applied and compared Logistic Regression and Decision Trees in conjunction with the feature selection Forward Wrapper method.

Results: We enrolled 120 SLE patients [M/F 8/112, median age 47.0 years (IQR 15.0); median disease duration 120.0 months (IQR 156.0)], 73.3% of them referring at least one episode of arthritis. Erosive damage was identified in 25.8% of patients (mean±SD 0.7±1.6), all of them with clinically evident arthritis. We applied Logistic Regression in conjunction with the Forward Wrapper method, obtaining an AUC value of 0.806±0.02. As a result of the learning procedure, we evaluated the relevance of the different factors: this value was higher than 35% for ACPA and anti-CarP.

Conclusion: The application of Machine Learning Models allowed to identify factors associated with US-detected erosive bone damage in a large SLE cohort and their relevance in determining this phenotype. Although the scope of this study is limited by the small sample size and its cross-sectional nature, the results suggest the relevance of ACPA and anti-CarP antibodies in the development of erosive damage as also pointed out in other studies.

MeSH terms

  • Adult
  • Anti-Citrullinated Protein Antibodies / blood
  • Arthritis / diagnostic imaging
  • Arthritis / etiology*
  • Arthritis / immunology
  • Autoantibodies / blood
  • Biomarkers / blood*
  • Cohort Studies
  • Cross-Sectional Studies
  • Decision Trees
  • Female
  • Humans
  • Logistic Models
  • Lupus Erythematosus, Systemic / complications*
  • Lupus Erythematosus, Systemic / immunology
  • Machine Learning*
  • Male
  • Middle Aged
  • Protein Carbamylation / immunology
  • Rheumatoid Factor / blood
  • Risk Factors
  • Ultrasonography

Substances

  • Anti-Citrullinated Protein Antibodies
  • Autoantibodies
  • Biomarkers
  • Rheumatoid Factor

Grants and funding

The authors received no specific funding for this work.