Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis.

Janne W. Bolt,Lisa G. M. van Baarsen,Maria C. Lebre,Saïda Aarrass,Dennis van der Coelen,Paul P. Tak,Marleen G. van de Sande,Marcel B. M. Teunissen,Daniëlle M. Gerlag,Arno W. van Kuijk

doi:10.3390/biomedicines10020324

Abstract

Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement.

Highlights

Psoriatic arthritis (PsA) is a chronic inflammatory joint disorder characterized by musculoskeletal manifestations such as arthritis, spondylitis, dactylitis spinal involvement and enthesitis, and extra articular features such as psoriatic skin lesions [1]
Results are shown as median integrated optical density (IOD)/mm2 and IQR of epidermis an and dermis of healthy donors (HDs) and PsA patients
Results are shown as median IOD/mm2 and IQR of epidermis and dermis of HD and NL skin

Summary

Introduction

Psoriatic arthritis (PsA) is a chronic inflammatory joint disorder characterized by musculoskeletal manifestations such as arthritis, spondylitis, dactylitis spinal involvement and enthesitis, and extra articular features such as psoriatic skin lesions [1]. Biomedicines 2022, 10, 324 biological (b) DMARDs, has drastically improved treatment outcomes in PsA. Disease remission is still not achieved in all PsA patients, and the efficacy of the various treatments differs from one person to the and can decrease over time [2]. IL-17A is the most widely studied and most biological active cytokine of the IL-17 family (IL17 A-F), and is produced by, e.g., CD4+ T cells, CD8+ T cells, gamma delta T cells, natural killer T cells (NKT), mast cells, and innate lymphoid cells [3–5]. Gene expression and protein levels of IL-17A, C and F are increased in affected skin lesions, nonlesional skin and synovial tissue of PsA patients [3,6], which result in the release of other pro-inflammatory cytokines and chemokines, the promotion of angiogenesis, and bone remodeling [7]. Little is known about the function of IL-17C and the other IL-17 family members (IL-17D and IL-17E) in PsA [8]

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