Novel signatures associated with systemic lupus erythematosus clinical response to IFN-α/-ω inhibition

Lupus. 2021 Apr;30(5):795-806. doi: 10.1177/0961203321995576. Epub 2021 Feb 24.


Objectives: We aimed to identify transcriptional gene signatures predictive of clinical response, for pharmacodynamic evaluation, and to provide mechanistic insight into JNJ-55920839, a human IgG1κ neutralizing mAb targeting IFN-α/IFN-ω, in participants with systemic lupus erythematosus (SLE).

Methods: Blood samples were obtained from SLE participants at baseline and up to Day 130, who received six 10 mg/kg IV doses of JNJ-55920839/placebo every 2 weeks. Participants with mild-to-moderate SLE who achieved clinical responses using SLE Disease Activity Index 2000 Responder Index 4-point change were considered responders. Transcriptional signatures from longitudinally collected blood were generated by RNA-Seq; signatures were generated by microarray from baseline blood samples exposed in vitro to JNJ-55920839 versus untreated.

Results: Two gene signatures (IFN-I Signaling and Immunoglobulin Immune Response) exhibited pharmacodynamic changes among JNJ-55920839 responders. The Immunoglobulin signature, but not the IFN-I signature, was elevated at baseline in JNJ-55920839 responders. A gene cluster associated with neutrophil-mediated immunity was reduced at baseline in JNJ-55920839 responders, substantiated by lower neutrophil counts in responders. An IFN-I signature was suppressed by JNJ-55920839 in vitro treatment versus untreated blood to a greater extent in responders before in vivo dosing.

Conclusions: These signatures may enable enrichment for treatment responders when using IFN-I-suppressing treatments in SLE.

Keywords: Systemic lupus erythematosus; biomarkers; monoclonal antibodies; precision medicine; transcription; type I interferon.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Administration, Intravenous
  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Biomarkers / blood
  • Case-Control Studies
  • Female
  • Humans
  • Immunoglobulins / genetics
  • Immunoglobulins / immunology
  • Interferon Type I / drug effects
  • Interferon Type I / genetics
  • Interferon-alpha / antagonists & inhibitors*
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / drug therapy*
  • Lupus Erythematosus, Systemic / genetics
  • Male
  • Middle Aged
  • Placebos / administration & dosage
  • Severity of Illness Index
  • Transcription, Genetic / genetics
  • Transcriptome / drug effects
  • Transcriptome / genetics
  • Ustekinumab / administration & dosage
  • Ustekinumab / pharmacology
  • Ustekinumab / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • Biomarkers
  • Immunoglobulins
  • Interferon Type I
  • Interferon-alpha
  • JNJ-55920839
  • Placebos
  • Ustekinumab