Cytokine Signatures in Psoriatic Arthritis Patients Indicate Different Phenotypic Traits Comparing Responders and Non-Responders of IL-17A and TNFα Inhibitors
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Cytokine Signatures in Psoriatic Arthritis Patients Indicate Different Phenotypic Traits Comparing Responders and Non-Responders of IL-17A and TNFα Inhibitors. / Skougaard, Marie; Ditlev, Sisse Bolm; Søndergaard, Magnus Friis; Kristensen, Lars Erik.
In: International Journal of Molecular Sciences, Vol. 24, No. 7, 6343, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Cytokine Signatures in Psoriatic Arthritis Patients Indicate Different Phenotypic Traits Comparing Responders and Non-Responders of IL-17A and TNFα Inhibitors
AU - Skougaard, Marie
AU - Ditlev, Sisse Bolm
AU - Søndergaard, Magnus Friis
AU - Kristensen, Lars Erik
N1 - Publisher Copyright: © 2023 by the authors.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - bDMARDs
KW - cytokines
KW - phenotypes
KW - principal component analysis
KW - psoriatic arthritis
U2 - 10.3390/ijms24076343
DO - 10.3390/ijms24076343
M3 - Journal article
C2 - 37047315
AN - SCOPUS:85152334393
VL - 24
JO - International Journal of Molecular Sciences (Online)
JF - International Journal of Molecular Sciences (Online)
SN - 1661-6596
IS - 7
M1 - 6343
ER -
ID: 387979034