Characterization of skin Th17 transcriptional profiles in psoriatic patients under adalimumab biotherapy.

Abstract

In psoriasis, a specific cytokine network has been described to play a central role in the pathophysiology of the disease. Anti-cytokine therapeutic approaches have been largely developed and TNFα constitutes the main target. Adalimumab is a human anti-TNFα monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation. We aimed to analyse changes in the skin inflammatory transcriptomic profile in psoriatic patients during adalimumab therapy. In addition, the circulating cytokine profile was analysed to define systemic inflammation. Eighteen patients with chronic plaque psoriasis were treated with adalimumab. After four and 16 weeks, clinical efficacy was assessed using PASI and DLQI, and skin mRNA profiles were determined and circulating cytokines quantified. We identified a rapid effect of adalimumab therapy on a large array of Th17 cytokines of the skin, which may account for the modification of keratinocyte expression profile and clinical response. In contrast, analysis of serum cytokine concentrations was uninformative, confirming the need for characterization of local cytokines in skin lesions. Finally, in non-responders, local cytokine expression was shown to be unchanged. We show that TNFα inhibition in psoriasis patients treated with adalimumab has a broad effect on the expression profile of cytokines and keratinocyte markers of skin inflammation, which may account for its clinical efficacy.

• Authors: Amandine Buffiere-Morgado, Elodie Couderc, Adriana Delwail, Laure Favot, Jean-François Jegou, Elisabeth Solau, Gérard Guillet, Jean-Claude Lecron, Frank Morel
• Journal: European journal of dermatology : EJD (Eur J Dermatol) Vol. 27 Issue 6 Pg. 579-589 (Dec 01 2017) ISSN: 1952-4013 [Electronic] France
• PMID: 29171393 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents
• Antibodies, Monoclonal
• Cytokines
• LINC00273 lncRNA, human
• Membrane Glycoproteins
• RNA, Long Noncoding
• RNA, Messenger
• Adalimumab

Topics

• Adalimumab (therapeutic use)
• Anti-Inflammatory Agents (therapeutic use)
• Antibodies, Monoclonal
• Biological Therapy
• Cytokines (metabolism)
• Gene Expression Profiling
• Humans
• Membrane Glycoproteins (metabolism)
• Psoriasis (drug therapy, immunology, metabolism)
• RNA, Long Noncoding
• RNA, Messenger (metabolism)
• Severity of Illness Index
• Skin (immunology, metabolism)
• Statistics, Nonparametric
• Th17 Cells
• Treatment Outcome