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

Marie Skougaard, Sisse Bolm Ditlev, Magnus Friis Søndergaard, Lars Erik Kristensen
Author Information
  1. Marie Skougaard: The Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark. ORCID
  2. Sisse Bolm Ditlev: Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark. ORCID
  3. Magnus Friis Søndergaard: Copenhagen Center for Translational Research, Bispebjerg and Frederiksberg Hospital, Bispebjerg Bakke 23, 2400 Copenhagen, Denmark.
  4. Lars Erik Kristensen: The Parker Institute, Bispebjerg and Frederiksberg Hospital, Nordre Fasanvej 57, 2000 Frederiksberg, Denmark.

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

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Grants

  1. OCAY-18-774-OFIL/Oak Foundation
  2. N/A/Elisabeth and Karl Ejnar Nis-Hanssens Mindelegat
  3. N/A/Minister Erna Hamiltons Legat for Videnskab og Kunst
  4. N/A/Overlæge Johan Boserup og Lise Boserups Legat
  5. I1F-NS-O004/Eli Lilly
  6. R188-A6597/The Danish Rheumatism Association

MeSH Term

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

Chemicals

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

Word Cloud

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