ArticleArthritis research & therapy2014
Heterogeneous expression pattern of interleukin 17A (IL-17A), IL-17F and their receptors in synovium of rheumatoid arthritis, psoriatic arthritis and osteoarthritis: possible explanation for nonresponse to anti-IL-17 therapy?
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
90 citing papers in PubMed, 2 syntheses or guidelines pooled it, 146 citations in OpenAlex.
- Association between the polymorphism of IL-17A and IL-17F gene with knee osteoarthritis risk: a meta-analysis based on case-control studies.Journal of orthopaedic surgery and research · 2019Pooled it
- Anti-IL-17 therapy in treatment of rheumatoid arthritis: a systematic literature review and meta-analysis of randomized controlled trials.Rheumatology international · 2016Pooled it
- Sonelokimab, an IL-17A/IL-17F-inhibiting nanobody for active psoriatic arthritis: a randomized, placebo-controlled phase 2 trial.Nature medicine · 2025Trial
- Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation.Annals of the rheumatic diseases · 2018Trial
- First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis.British journal of clinical pharmacology · 2017Trial
- The Pathophysiological Significance of Dual Inhibition of IL-17A and IL-17F in Psoriatic Arthritis and Axial Spondyloarthritis.Mediterranean journal of rheumatology · 2026Review
- Aptamers Targeting IL17A and Its Receptor Suppress IL17 Signaling in Different Cell Types.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Tildrakizumab as a Potential Option for Early Psoriatic Arthritis in Patients with Metabolic Comorbidities and Psoriasis: a Case Series.Dermatology practical & conceptual · 2025Article
- The Therapeutic Potential of Phytochemicals Unlocks New Avenues in the Management of Rheumatoid Arthritis.International journal of molecular sciences · 2025Review
- Relation of Cytokine Profile and Antibody Values to Post-Translational Protein Modifications in Patients with Rheumatoid Arthritis (Preliminary Data).Doklady. Biochemistry and biophysics · 2025Article
- Serum Interleukin-17 and Its Association with Inflammation and Bone Remodeling in Rheumatoid Arthritis and Hand Osteoarthritis: Insights from Musculoskeletal Ultrasound.Diagnostics (Basel, Switzerland) · 2025Article
- Secukinumab in refractory non-infectious anterior uveitis.Frontiers in ophthalmology · 2025Article
- Review
- Patterns and determinants of response to novel therapies in juvenile and adult-onset polyarthritis.Rheumatology (Oxford, England) · 2024Review
- Role of Interleukin-17 family cytokines in disease severity of patients with knee osteoarthritis.Advances in rheumatology (London, England) · 2024Article
- Differential effects of interleukin-17A and 17F on cell interactions between immune cells and stromal cells from synovium or skin.Scientific reports · 2023Article
- Psoriatic disease and non-alcoholic fatty liver disease shared pathogenesis review.Seminars in arthritis and rheumatism · 2023Review
- Bimekizumab Efficacy and Safety in Japanese Patients with Plaque Psoriasis in BE VIVID: A Phase 3, Ustekinumab and Placebo-Controlled Study.Dermatology and therapy · 2023Article
- The role of retinoic acid receptor-related orphan receptors in skeletal diseases.Frontiers in endocrinology · 2023Review
- Mucosal-associated invariant T cells in patients with axial spondyloarthritis.Frontiers in immunology · 2023Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionAccumulating evidence suggests an important role for interleukin 17 (IL-17) in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Accordingly, clinical trials aimed at blocking IL-17 have been initiated, but clinical results between patients and across different diseases have been highly variable. The objective was to determine the variability in expression of IL-17A, IL-17F and their receptors IL-17RA and IL-17RC in the synovia of patients with arthritis.
methodsSynovial biopsies were obtained from patients with RA (n = 11), PsA (n = 15) and inflammatory osteoarthritis (OA, n = 14). For comparison, synovia from noninflamed knee joints (n = 7) obtained from controls were included. Frozen sections were stained for IL-17A, IL-17F, IL-17RA and IL-17RC and evaluated by digital image analysis. We used confocal microscopy to determine which cells in the synovium express IL-17A and IL-17F, double-staining with CD4, CD8, CD15, CD68, CD163, CD31, von Willebrand factor, peripheral lymph node address in, lymphatic vessel endothelial hyaluronan receptor 1, mast cell tryptase and retinoic acid receptor-related orphan receptor γt (RORγt).
resultsIL-17A, IL-17F, IL-17RA and IL-17RC were abundantly expressed in synovial tissues of all patient groups. Whereas IL-17RA was present mostly in the synovial sublining, IL-17RC was abundantly expressed in the intimal lining layer. Digital image analysis showed a significant (P < 0.05) increase of only IL-17A in arthritis patients compared to noninflamed control tissues. The expression of IL-17A, IL-17F and their receptors was similar in the different patient groups, but highly variable between individual patients. CD4+ and CD8+ cells coexpressed IL-17A, and few cells coexpressed IL-17F. IL-17A and IL-17F were not expressed by CD15+ neutrophils. Mast cells were only occasionally positive for IL-17A or IL-17F. Interestingly, IL-17A and IL-17F staining was also observed in macrophages, as well as in blood vessels and lymphatics. This staining probably reflects receptor-bound cytokine staining. Many infiltrated cells were positive for the transcription factor RORγt. Colocalisation between RORγt and IL-17A and IL-17F indicates local IL-17 production.
conclusionsIncreased expression of IL-17A is not restricted to synovial tissues of RA and PsA patients; it is also observed in inflammatory OA. The heterogeneous expression levels may explain nonresponse to anti-IL-17 therapy in subsets of patients.
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