Proteomic analysis to define predictors of treatment response to adalimumab or methotrexate in rheumatoid arthritis patients

Pharmacogenomics J. 2020 Jun;20(3):516-523. doi: 10.1038/s41397-019-0139-4. Epub 2019 Dec 10.

Abstract

Seropositivity for anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA), a chronic autoimmune arthritis, is associated with worse long-term disease outcomes. ACPA is ubiquitously tested in RA patients, but other autoantibodies exist (in both citrullinated and non-citrullinated form) which may provide additional information on RA subtypes and/or treatment response. We used a multiplex bead-based assay of 376 autoantibodies to test associations between these autoantibodies and treatment response in RA patients. Clusters of patients with similar autoantibody expression were defined and cluster membership was associated with treatment response. Thirty-four autoantibodies were differentially expressed in RA patients compared with healthy controls; citrullinated vimentin was associated with treatment response. A selection of citrullinated autoantibodies was found to be associated with treatment response in a subanalysis of ACPA-negative RA patients. Finer ACPA specificities in ACPA-negative RA patients may be predictive of treatment response and could represent a rich vein of future study.

Publication types

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

MeSH terms

  • Adalimumab / therapeutic use*
  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / epidemiology
  • Arthritis, Rheumatoid / genetics*
  • Autoantibodies / genetics
  • Cohort Studies
  • Female
  • Germany / epidemiology
  • Humans
  • Male
  • Methotrexate / therapeutic use*
  • Middle Aged
  • Predictive Value of Tests
  • Prospective Studies
  • Proteomics / methods*
  • Treatment Outcome
  • United Kingdom / epidemiology

Substances

  • Antirheumatic Agents
  • Autoantibodies
  • Adalimumab
  • Methotrexate