IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors
| العنوان: | IL-23 skin and joint profiling in psoriatic arthritis: novel perspectives in understanding clinical responses to IL-23 inhibitors |
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| المؤلفون: | Nirupam Purkayastha, Myles Lewis, Katriona Goldmann, W.S. Tan, Alessandra Nerviani, Stephen Kelly, Marie-Astrid Boutet, Tamás Lajtos, Costantino Pitzalis, Rebecca Hands |
| المصدر: | Annals of the Rheumatic Diseases |
| بيانات النشر: | BMJ, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, 0301 basic medicine, Pathology, medicine.medical_specialty, Psoriatic Arthritis, Immunology, Arthritis, Interleukin-23, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Psoriatic arthritis, 0302 clinical medicine, Rheumatology, Synovitis, Ustekinumab, medicine, Interleukin 23, Humans, Immunology and Allergy, Skin, 030203 arthritis & rheumatology, Principal Component Analysis, Molecular pathology, business.industry, Gene Expression Profiling, Arthritis, Psoriatic, Interleukin-17, Synovial Membrane, Interleukin, Middle Aged, medicine.disease, Treatment Outcome, 030104 developmental biology, arthritis, biological therapy, Antirheumatic Agents, Immunohistochemistry, Female, Tumor Necrosis Factor Inhibitors, psoriatic, business, medicine.drug |
| الوصف: | ObjectivesTo determine the relationship between synovial versus skin transcriptional/histological profiles in patients with active psoriatic arthritis (PsA) and explore mechanistic links between diseased tissue pathology and clinical outcomes.MethodsTwenty-seven active PsA patients were enrolled in an observational/open-label study and underwent biopsies of synovium and paired lesional/non-lesional skin before starting anti-tumour necrosis factor (TNF) (if biologic-naïve) or ustekinumab (if anti-TNF inadequate responders). Molecular analysis of 80-inflammation-related genes and protein levels for interleukin (IL)-23p40/IL-23p19/IL-23R were assessed by real-time-PCR and immunohistochemistry, respectively.ResultsAt baseline, all patients had persistent active disease as per inclusion criteria. At primary end-point (16-weeks post-treatment), skin responses favoured ustekinumab, while joint responses favoured anti-TNF therapies. Principal component analysis revealed distinct clustering of synovial tissue gene expression away from the matched skin. While IL12B, IL23A and IL23R were homogeneously expressed in lesional skin, their expression was extremely heterogeneous in paired synovial tissues. Here, IL-23 transcriptomic/protein expression was strongly linked to patients with high-grade synovitis who, however, were not distinguishable by conventional clinimetric measures.ConclusionsPsA synovial tissue shows a heterogeneous IL-23 axis profile when compared with matched skin. Synovial molecular pathology may help to identify among clinically indistinguishable patients those with a greater probability of responding to IL-23 inhibitors. |
| تدمد: | 1468-2060 0003-4967 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b6a9eb1d14d750c870bd378942d36860Test https://doi.org/10.1136/annrheumdis-2020-218186Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b6a9eb1d14d750c870bd378942d36860 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14682060 00034967 |
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