TY - JOUR
T1 - Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis
AU - Bolt, Janne W.
AU - van Kuijk, Arno W.
AU - Teunissen, Marcel B. M.
AU - van der Coelen, Dennis
AU - Aarrass, Saïda
AU - Gerlag, Daniëlle M.
AU - Tak, Paul P.
AU - van de Sande, Marleen G.
AU - Lebre, Maria C.
AU - van Baarsen, Lisa G. M.
N1 - Funding Information: Funding: This research was funded the Innovative Medicines Initiatives (IMI) European Union (EU) funded project BeTheCure (nr115142) and ZonMw VIDI grant (nr91718371). The clinical part of the study was funded by Abbott BV, The Netherlands. Abbot BV had no role in the study design or in the collection, analysis, or interpretation of the data, the writing of this manuscript, or the decision to submit the manuscript for publication. Publication of this article was not contingent upon approval by Abbot BV. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/2/1
Y1 - 2022/2/1
N2 - 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.
AB - 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.
KW - Adalimumab
KW - Immunohistochemistry
KW - Immunopathogenesis
KW - Interleukin-17
KW - Psoriatic arthritis
KW - Skin
KW - Synovium
UR - http://www.scopus.com/inward/record.url?scp=85124099798&partnerID=8YFLogxK
U2 - https://doi.org/10.3390/biomedicines10020324
DO - https://doi.org/10.3390/biomedicines10020324
M3 - Article
C2 - 35203534
SN - 2227-9059
VL - 10
JO - Biomedicines
JF - Biomedicines
IS - 2
M1 - 324
ER -