Cytokine Signatures in Psoriatic Arthritis Patients Indicate Different Phenotypic Traits Comparing Responders and Non-Responders of IL-17A and TNFα Inhibitors

Int J Mol Sci. 2023 Mar 28;24(7):6343. doi: 10.3390/ijms24076343.

Abstract

This study aimed to explore the dynamic interactions between 32 cytokines and biomarkers in Psoriatic Arthritis (PsA) patients to compare cytokine signatures of treatment responders and non-responders. Biomarkers were measured before and after four months of treatment in 39 PsA patients initiating either Tumor Necrosis Factor alpha inhibitor (TNFi) or Interleukin-17A inhibitor (IL-17Ai). Response to treatment was defined by the composite measure, Disease Activity in Psoriatic Arthritis (DAPSA). A two-component principal component analysis (PCA) was implemented to describe cytokine signatures comparing DAPSA50 responders and non-responders. The cytokine signature of TNFi responders was driven by the correlated cytokines interferon γ (IFNγ) and IL-6, additionally associated with IL-12/IL-23p40, TNFα, and CRP, while the cytokine signature of TNFi non-responders was driven by the correlated cytokines IL-15, IL-8, and IFNγ. IL-17Ai responders were characterized by contributions of strongly correlated Th17 inflammatory cytokines, IL-17A, IL-12/IL-23p40, IL-22 to the cytokine signature, whereas IL-17A and IL-12/IL-23p40 did not demonstrate significant contribution in IL-17Ai non-responders. Based on PCA results it was possible to differentiate DAPSA50 responders and non-responders to treatment, endorsing additional examination of cytokine interaction models in PsA patients and supporting further PsA patient immune stratification to improve individualized treatment of PsA patients.

Keywords: bDMARDs; cytokines; phenotypes; principal component analysis; psoriatic arthritis.

MeSH terms

  • Arthritis, Psoriatic*
  • Cytokines
  • Humans
  • Interferon-gamma
  • Interleukin-12
  • Interleukin-17
  • Tumor Necrosis Factor-alpha

Substances

  • Tumor Necrosis Factor-alpha
  • Cytokines
  • Interleukin-17
  • Interferon-gamma
  • Interleukin-12