Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse

Ann Rheum Dis. 2019 Dec;78(12):1669-1676. doi: 10.1136/annrheumdis-2019-215571. Epub 2019 Sep 30.

Abstract

Objectives: Maintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.

Methods: A total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.

Results: Of all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.

Conclusion: Direct serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.

Keywords: biomarker; flare; interferon-alpha; low disease activity; relapse; remission; systemic lupus erythematosus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autoantibodies / immunology
  • Biomarkers / blood
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoassay
  • Interferon-alpha / blood*
  • Interferon-alpha / immunology
  • Lupus Erythematosus, Systemic / blood*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Recurrence
  • Reproducibility of Results
  • Retrospective Studies
  • Risk Factors
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Biomarkers
  • Interferon-alpha