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

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Andres-Ejarque, Rosa  ORCID logo
Ale, Hira Bahadur 
Grys, Katarzyna 
Tosi, Isabella 
Solanky, Shane 


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+ T cells in the blood of non-responders before therapy. Moreover, lesional skin of non-responders contains higher numbers of dermal DC expressing the maturation marker CD83 and producing IL-23, and increased numbers of IL-17+ T cells. Finally, we identify and clinically validate LPS-induced NF-κBp65 phosphorylation before therapy as a predictive biomarker of non-response to adalimumab, with 100% sensitivity and 90.1% specificity in an independent cohort. Our study uncovers important molecular and cellular mediators underpinning adalimumab mechanisms of action in psoriasis and we propose a blood biomarker for predicting clinical outcome.


Funder: Department of Health


Adalimumab, B7-H1 Antigen, Biological Therapy, Biomarkers, Dendritic Cells, Humans, Interleukin-17, Lipopolysaccharides, Lymphocytes, NF-kappa B, Phosphorylation, Psoriasis, Sensitivity and Specificity, Signal Transduction, Tumor Necrosis Factor Inhibitors, Tumor Necrosis Factor-alpha

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Nat Commun

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Springer Science and Business Media LLC
Medical Research Council (MR/L011808/1, MR/S003126/1)