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

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cam.issuedOnline2022-01-29
dc.contributor.authorBolt, Janne W
dc.contributor.authorvan Kuijk, Arno W
dc.contributor.authorTeunissen, Marcel BM
dc.contributor.authorvan der Coelen, Dennis
dc.contributor.authorAarrass, Saïda
dc.contributor.authorGerlag, Daniëlle M
dc.contributor.authorTak, Paul P
dc.contributor.authorvan de Sande, Marleen G
dc.contributor.authorLebre, Maria C
dc.contributor.authorvan Baarsen, Lisa GM
dc.contributor.orcidBolt, Janne W [0000-0001-5065-7439]
dc.contributor.orcidTeunissen, Marcel BM [0000-0003-1119-6662]
dc.contributor.orcidTak, Paul P [0000-0002-3532-5409]
dc.contributor.orcidvan Baarsen, Lisa GM [0000-0003-3346-8921]
dc.date.accessioned2022-03-28T19:07:09Z
dc.date.available2022-03-28T19:07:09Z
dc.date.issued2022-01-29
dc.date.updated2022-03-28T19:07:09Z
dc.descriptionFunder: Abbot BV, The Netherlands
dc.description.abstractInterleukin (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.
dc.identifier.doi10.17863/CAM.82857
dc.identifier.eissn2227-9059
dc.identifier.issn2227-9059
dc.identifier.other35203534
dc.identifier.otherPMC8869729
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335428
dc.languageeng
dc.language.isoeng
dc.publisherMDPI AG
dc.publisher.urlhttp://dx.doi.org/10.3390/biomedicines10020324
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 2227-9059
dc.sourcenlmid: 101691304
dc.subjectadalimumab
dc.subjectimmunohistochemistry
dc.subjectimmunopathogenesis
dc.subjectinterleukin-17
dc.subjectpsoriatic arthritis
dc.subjectskin
dc.subjectsynovium
dc.titleImpact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis.
dc.typeArticle
dcterms.dateAccepted2022-01-24
prism.issueIdentifier2
prism.publicationNameBiomedicines
prism.volume10
pubs.funder-project-idZonMw VIDI grant (91718371)
pubs.funder-project-idThe IMI EU funded project BeTheCure (115142)
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
rioxxterms.versionVoR
rioxxterms.versionofrecord10.3390/biomedicines10020324

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