Enhanced NF-κB signaling in type-2 dendritic cells at baseline predicts non-response to adalimumab in psoriasis.

Adalimumab / therapeutic use B7-H1 Antigen Biological Therapy Biomarkers / blood Dendritic Cells / drug effects Humans Interleukin-17 Lipopolysaccharides / adverse effects Lymphocytes NF-kappa B / metabolism Phosphorylation Psoriasis / immunology Sensitivity and Specificity Signal Transduction Tumor Necrosis Factor Inhibitors Tumor Necrosis Factor-alpha

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
06 08 2021
Historique:
received: 19 10 2020
accepted: 24 06 2021
entrez: 7 8 2021
pubmed: 8 8 2021
medline: 24 8 2021
Statut: epublish

Résumé

Biologic therapies have transformed the management of psoriasis, but clinical outcome is variable leaving an unmet clinical need for predictive biomarkers of response. Here we perform in-depth immunomonitoring of blood immune cells of 67 patients with psoriasis, before and during therapy with the anti-TNF drug adalimumab, to identify immune mediators of clinical response and evaluate their predictive value. Enhanced NF-κBp65 phosphorylation, induced by TNF and LPS in type-2 dendritic cells (DC) before therapy, significantly correlates with lack of clinical response after 12 weeks of treatment. The heightened NF-κB activation is linked to increased DC maturation in vitro and frequency of IL-17

Identifiants

DOI: 10.1038/s41467-021-25066-9 PMID: 34362923 PMC: PMC8346545
pubmed: 34362923
doi: 10.1038/s41467-021-25066-9
pii: 10.1038/s41467-021-25066-9
pmc: PMC8346545
doi:

Substances chimiques

B7-H1 Antigen 0
Biomarkers 0
IL17A protein, human 0
Interleukin-17 0
Lipopolysaccharides 0
NF-kappa B 0
Tumor Necrosis Factor Inhibitors 0
Tumor Necrosis Factor-alpha 0
Adalimumab FYS6T7F842

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

4741

Subventions

Organisme : Medical Research Council
ID : MR/L011808/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S003126/1
Pays : United Kingdom

Investigateurs

Paola Di Meglio (P)
Richard Emsley (R)
Andrea Evans (A)
Katherine Payne (K)
Deborah Stocken (D)

Commentaires et corrections

Type : ErratumIn

Informations de copyright

© 2021. The Author(s).

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Auteurs

Rosa Andres-Ejarque (R)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
ORCID: 0000-0003-0012-1155

Hira Bahadur Ale (HB)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.

Katarzyna Grys (K)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Isabella Tosi (I)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Shane Solanky (S)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.

Chrysanthi Ainali (C)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
DIGNOSIS Limited, London, UK.

Zeynep Catak (Z)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Hemawtee Sreeneebus (H)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Jake Saklatvala (J)

Department of Medical and Molecular Genetics, Kings College London, London, UK.
ORCID: 0000-0003-0836-4928

Nick Dand (N)

Department of Medical and Molecular Genetics, Kings College London, London, UK.
ORCID: 0000-0002-1805-6278

Emanuele de Rinaldis (E)

NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.
Sanofi, Cambridge, MA, USA.

Anna Chapman (A)

Dermatology Department, Queen Elizabeth Hospital, Lewisham and Greenwich NHS Trust, London, UK.

Frank O Nestle (FO)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.
Sanofi, Cambridge, MA, USA.

Michael R Barnes (MR)

Centre for Translational Bioinformatics, William Harvey Research Institute, Queen Mary University of London, Charterhouse Square, London, UK.
ORCID: 0000-0001-9097-7381

Richard B Warren (RB)

Dermatology Centre, Salford Royal Hospital, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Nick J Reynolds (NJ)

Institute of Translational and Clinical Medicine, Newcastle University Medical School and Department of Dermatology, Royal Victoria Infirmary, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.

Christopher E M Griffiths (CEM)

Dermatology Centre, Salford Royal Hospital, The University of Manchester, Manchester Academic Health Science Centre, Manchester, UK.

Jonathan N Barker (JN)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Catherine H Smith (CH)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK.

Paola Di Meglio (P)

St. Johns Institute of Dermatology, Kings College London, London, United Kingdom. paola.dimeglio@kcl.ac.uk.
NIHR Biomedical Research Centre, Guys & St Thomas NHS Foundation Trust & King's College London, London, UK. paola.dimeglio@kcl.ac.uk.
ORCID: 0000-0002-2066-7780

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Classifications MeSH

questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Anticorps monoclonaux humanisés › Adalimumab › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Antigènes B7 › Antigène CD274 › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Thérapeutique › Biothérapie › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Système phagocytaire mononucléé › Cellules dendritiques › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Interleukines › Interleukine-17 › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Facteurs biologiques › Toxines biologiques › Toxines bactériennes › Endotoxines › Lipopolysaccharides › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Facteur de transcription NF-kappa B › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Métabolisme › Phosphorylation › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Dermatoses papulosquameuses › Psoriasis › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Sensibilité et spécificité › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Anti-inflammatoires › Inhibiteurs du facteur de nécrose tumorale › Enhanced NF-κB signaling in type-2 dendritic...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Cytokines › Facteurs de nécrose tumorale › Facteur de nécrose tumorale alpha › Enhanced NF-κB signaling in type-2 dendritic...