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

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.

Figure 1

PCA correlation plot including biomarkers of PsA patients initiating TNFi. Correlation plots retrieved from the principal component analysis visualize the relationship between individual biomarker and the components. Component 1 and 2 uncorrelated described with the perpendicular axes from −1.0 to 1.0. The degree of contribution to the immune signature is illustrated with red representing strong contribution to the component and black representing minor contribution. TNFi; Tumor Necrosis Factor-alpha inhibitor, basic Fibroblast Growth Factor, Flt-1; Fms related Receptor Tyrosine Kinase-1, VEGFR1; Vascular Endothelial Growth Factor Receptor 1, PlGF; Placental Growth Factor, Tie-2; endothelial receptor tyrosine kinase, VEGF; Vascular Endothelial Growth Factor, IP-10; IFN-induced protein-10, CXCL; CXC chemokine ligand, MCP; monocyte chemo-attractant protein, CCL; CC chemokine ligand, MDC; macrophage-derived chemokine, MIP; macrophage inflammatory protein, TARC; Thymus and activation regulated chemokine, IL; interleukin, IL-1RA; interleukin 1 receptor antagonist, IFN; interferon, TNF; Tumor Necrosis Factor, CRP; C-reactive protein, ICAM; Intercellular Adhesion Molecule, VCAM; Vascular Cell Adhesion Molecule.

Figure 2

PCA correlation plot including biomarkers of PsA patients initiating IL-17Ai. Correlation plots retrieved from the principal component analysis visualize the relationship between individual biomarker and the components. Component 1 and 2 uncorrelated described with the perpendicular axes from −1.0 to 1.0. The degree of contribution to the immune signature is illustrated with red representing strong contribution to the component and black representing minor contribution. IL-17i; Interleukin 17 inhibitor, basic Fibroblast Growth Factor, Flt-1; Fms related Receptor Tyrosine Kinase-1, VEGFR1; Vascular Endothelial Growth Factor Receptor 1, PlGF; Placental Growth Factor, Tie-2; endothelial receptor tyrosine kinase, VEGF; Vascular Endothelial Growth Factor, IP-10; IFN-induced protein-10, CXCL; CXC chemokine ligand, MCP; monocyte chemoattractant protein, CCL; CC chemokine ligand, MDC; macrophage-derived chemokine, MIP; macrophage inflammatory protein, TARC; Thymus and activation regulated chemokine, IL; interleukin, IL-1RA; interleukin 1 receptor antagonist, IFN; interferon, TNF; Tumor Necrosis Factor, CRP; C-reactive protein, ICAM; Intercellular Adhesion Molecule, VCAM; Vascular Cell Adhesion Molecule.