Cytokine responses in nonlesional psoriatic skin as clinical predictor to anti-TNF agents.
PASI
Psoriasis
cytokine response
drug response prediction
etanercept
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
04
01
2021
revised:
14
06
2021
accepted:
20
07
2021
pubmed:
4
8
2021
medline:
4
3
2022
entrez:
3
8
2021
Statut:
ppublish
Résumé
A major issue with the current management of psoriasis is our inability to predict treatment response. Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for patients with psoriasis. We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in more than 200 RNA-seq samples. We demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in nonlesional, but not lesional, skin were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with Psoriasis Area and Severity Index (PASI) improvement (P = 9.8 × 10 Our results illustrate feasibility of assessing drug response in psoriasis using nonlesional skin and implicate involvement of IFN regulators in anti-TNF responses.
Sections du résumé
BACKGROUND
A major issue with the current management of psoriasis is our inability to predict treatment response.
OBJECTIVE
Our aim was to evaluate the ability to use baseline molecular expression profiling to assess treatment outcome for patients with psoriasis.
METHODS
We conducted a longitudinal study of 46 patients with chronic plaque psoriasis treated with anti-TNF agent etanercept, and molecular profiles were assessed in more than 200 RNA-seq samples.
RESULTS
We demonstrated correlation between clinical response and molecular changes during the course of the treatment, particularly for genes responding to IL-17A/TNF in keratinocytes. Intriguingly, baseline gene expressions in nonlesional, but not lesional, skin were the best marker of treatment response at week 12. We identified USP18, a known regulator of IFN responses, as positively correlated with Psoriasis Area and Severity Index (PASI) improvement (P = 9.8 × 10
CONCLUSIONS
Our results illustrate feasibility of assessing drug response in psoriasis using nonlesional skin and implicate involvement of IFN regulators in anti-TNF responses.
Identifiants
pubmed: 34343561
pii: S0091-6749(21)01144-1
doi: 10.1016/j.jaci.2021.07.024
pmc: PMC9451046
mid: NIHMS1733498
pii:
doi:
Substances chimiques
Cytokines
0
Tumor Necrosis Factor Inhibitors
0
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
640-649.e5Subventions
Organisme : NIAMS NIH HHS
ID : K08 AR060802
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR056802
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIAMS NIH HHS
ID : L40 AR076139
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR072773
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR069071
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075049
Pays : United States
Organisme : NIAMS NIH HHS
ID : P30 AR075043
Pays : United States
Organisme : NIAMS NIH HHS
ID : K01 AR072129
Pays : United States
Informations de copyright
Copyright © 2021 American Academy of Allergy, Asthma & Immunology. All rights reserved.
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