Entheseal tissue signature in response to IL-17A inhibition in psoriatic arthritis: results from the EBIO entheseal biopsy study

Raimondo MG, Mohammadian H, Rauber S, Alivernini S, Fedorchenko V, Rigau AR, Angeli MR, Fagni F, Corte G, Tascilar K, Labinsky H, Ramming A, Roemer F, Rech J, Bräuer L, D'Agostino MA, Schett G, Pachowsky M, Kleyer A, Ramming A (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Annals of the Rheumatic Diseases BMJ Publishing Group

DOI: 10.1016/j.ard.2025.08.032

Abstract

Objectives: Enthesitis, a hallmark of psoriatic arthritis (PsA), reflects the interplay between mechanical stress and immune dysregulation at tendon-bone interfaces. This study investigates the cellular and molecular responses in entheseal tissues following interleukin (IL)-17A inhibition in patients with active PsA. Methods: In this prospective, interventional phase 4 trial, we enrolled 10 patients with enthesitis of the lateral epicondyle, performed entheseal biopsies, and analysed tissues by imaging mass cytometry (IMC) and spatial transcriptomics before and after treatment. Results: Following 24 weeks of IL-17A inhibition, 9/10 patients of the cohort clinically responded to treatment as assessed by Disease Activity in Psoriatic Arthritis (DAPSA), Spondyloarthritis research consortium of canada (SPARCC) score, and power Doppler sonography. IMC analysis showed significant reductions of enthesitis-related immune cell populations, in particular IL-17-producing CD4, CD8, CD4^neg/CD8^negT cells, granulocytes, and innate lymphoid cells type 3. Spatial transcriptomics revealed that CD200+DKK3+ fibroblasts and innate lymphoid cells type 2 expanded and formed an anti-inflammatory niche upon treatment. Notably, IL-17A inhibition led to decreased osteoblast differentiation markers, suggesting a potential mechanism to inhibit pathological bone formation. Conclusions: These findings underline the pivotal role of IL-17A in enthesitis, showing that IL-17A inhibition profoundly modulates the tissue microenvironment of entheses in PsA.

Authors with CRIS profile

Maria Gabriella Raimondo Department of Medicine 3 – Rheumatology and Immunology Hashem Mohammadian Department of Medicine 3 – Rheumatology and Immunology Simon Rauber Department of Medicine 3 – Rheumatology and Immunology Aleix Rius Rigau Department of Medicine 3 – Rheumatology and Immunology Mario Raphael Angeli Department of Medicine 3 – Rheumatology and Immunology Filippo Fagni Department of Medicine 3 – Rheumatology and Immunology Koray Tascilar Department of Medicine 3 – Rheumatology and Immunology Hannah Labinsky Department of Medicine 3 – Rheumatology and Immunology Alina Ramming Department of Medicine 3 – Rheumatology and Immunology Frank Roemer Institute of Radiology Jürgen Rech Department of Medicine 3 – Rheumatology and Immunology Lars Bräuer Professur für Oberflächenaktive Proteine Georg Schett Lehrstuhl für Innere Medizin III Milena Pachowsky Department of Medicine 3 – Rheumatology and Immunology Arnd Kleyer Department of Medicine 3 – Rheumatology and Immunology Andreas Ramming Medizinische Fakultät

Involved external institutions

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Italy (IT)

How to cite

APA:

Raimondo, M.G., Mohammadian, H., Rauber, S., Alivernini, S., Fedorchenko, V., Rigau, A.R.,... Ramming, A. (2025). Entheseal tissue signature in response to IL-17A inhibition in psoriatic arthritis: results from the EBIO entheseal biopsy study. Annals of the Rheumatic Diseases. https://doi.org/10.1016/j.ard.2025.08.032

MLA:

Raimondo, Maria Gabriella, et al. "Entheseal tissue signature in response to IL-17A inhibition in psoriatic arthritis: results from the EBIO entheseal biopsy study." Annals of the Rheumatic Diseases (2025).

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