Skip to main content

ORIGINAL RESEARCH article

Front. Immunol.
Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1455134

Serum IL-23 levels reflect a myeloid inflammatory signature and predict the response to apremilast in patients with psoriatic arthritis

Provisionally accepted
Maria De Santis Maria De Santis 1,2Antonio Tonutti Antonio Tonutti 1,2Natasa Isailovic Natasa Isailovic 2Francesca Motta Francesca Motta 1,2Radu Marian Rivara Radu Marian Rivara 2Rita Ragusa Rita Ragusa 2Giacomo M. Guidelli Giacomo M. Guidelli 2Marta Caprioli Marta Caprioli 2Angela Ceribelli Angela Ceribelli 1,2Daniela Renna Daniela Renna 2Nicoletta Luciano Nicoletta Luciano 1,2Carlo Selmi Carlo Selmi 1,2*
  • 1 Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy
  • 2 Rheumatology and Clinical Immunology, Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Humanitas Research Hospital, Rozzano, Italy

The final, formatted version of the article will be published soon.

    Background. The phosphodiesterase 4 (PDE4) inhibitor apremilast downregulates the production of IL-23 and other pro-inflammatory cytokines involved in the pathogenesis of psoriatic arthritis (PsA).Aim. To investigate the effects of apremilast on the production of cytokines by peripheral blood monocyte-derived macrophages, innate-like lymphocyte cells (ILCs), mucosal-associated invariant T (MAIT) cells, γδ T cells, natural killer (NK) cells, and NKT-like cells from patients with PsA manifesting different clinical responses to the treatment.Methods. Peripheral blood samples were obtained from patients with PsA at baseline and after 1 and 4 months of apremilast therapy (n=23) and 20 controls with osteoarthritis. Cytokine expression in peripheral blood monocyte-derived macrophages and ILCs/MAIT/γδT/NK/NKT-like cells was tested by RT-PCR and FACS analysis, respectively; cytokine levels in culture supernatants and sera were analyzed by ELISA.Results. PsA monocyte-derived macrophages exhibited higher expression of IL-23, IL-1β, and TNFα, compared to OA controls, more profoundly in patients responding to apremilast. Seventeen/23 (74%) PsA patients were classified as responders to apremilast at 4 months and a baseline serum IL-23 >1.4 pg/mL was associated with the responder status (AUCROC 0.79; sensitivity 100%, specificity 68%). Of note, apremilast led to a significant reduced expression of IL-23 in peripheral blood monocyte-derived macrophages; IL-17 in ILC1 and in T cells of responder patients; IFN-γ in γδ T lymphocytes.Conclusion. An enhanced myeloid inflammatory signature characterizes PsA monocyte-derived macrophages and serum IL-23 levels represent candidate biomarkers for PsA response to apremilast.

    Keywords: Spondyloarthritis (including psoriatic arthritis), precision medicine, immunology, Cytokines, innate lymphocyte, Macrophages

    Received: 26 Jun 2024; Accepted: 18 Nov 2024.

    Copyright: © 2024 De Santis, Tonutti, Isailovic, Motta, Rivara, Ragusa, Guidelli, Caprioli, Ceribelli, Renna, Luciano and Selmi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Carlo Selmi, Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.