Histone modifications associated with biological drug response in moderate-to-severe psoriasis
- PMID: 30260532
- DOI: 10.1111/exd.13790
Histone modifications associated with biological drug response in moderate-to-severe psoriasis
Abstract
Introduction: Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate-to-severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies.
Objective: To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab).
Materials and methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM-SPSS v.23.
Results and conclusions: Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non-significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non-responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non-responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients' response to biological drugs in psoriasis.
Keywords: biological drugs; biomarkers; epigenetics; pharmacoepigenetics; psoriatic arthritis.
© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Similar articles
-
Abnormal histone modifications in PBMCs from patients with psoriasis vulgaris.Eur J Dermatol. 2011 Jul-Aug;21(4):552-7. doi: 10.1684/ejd.2011.1383. Eur J Dermatol. 2011. PMID: 21715244
-
Treatment of psoriasis and psoriatic arthritis.BioDrugs. 2013 Jan;27 Suppl 1:3-12. doi: 10.1007/BF03325637. BioDrugs. 2013. PMID: 23990277 Review.
-
Ixekizumab for treatment of adults with moderate-to-severe plaque psoriasis and psoriatic arthritis.Expert Rev Clin Pharmacol. 2016 Nov;9(11):1423-1433. doi: 10.1080/17512433.2016.1242409. Epub 2016 Oct 11. Expert Rev Clin Pharmacol. 2016. PMID: 27690669 Review.
-
Therapeutic strategies in psoriasis patients with psoriatic arthritis: focus on new agents.BioDrugs. 2013 Aug;27(4):359-73. doi: 10.1007/s40259-013-0025-6. BioDrugs. 2013. PMID: 23580094 Review.
-
Pharmacogenetics and Pharmacogenomics in Moderate-to-Severe Psoriasis.Am J Clin Dermatol. 2018 Apr;19(2):209-222. doi: 10.1007/s40257-017-0322-9. Am J Clin Dermatol. 2018. PMID: 28921458 Review.
Cited by
-
Dietary compounds as potential modulators of microRNA expression in psoriasis.Ther Adv Chronic Dis. 2019 Aug 7;10:2040622319864805. doi: 10.1177/2040622319864805. eCollection 2019. Ther Adv Chronic Dis. 2019. PMID: 31431821 Free PMC article. Review.
-
Chronic Inflammation as the Underlying Mechanism of the Development of Lung Diseases in Psoriasis: A Systematic Review.Int J Mol Sci. 2022 Feb 4;23(3):1767. doi: 10.3390/ijms23031767. Int J Mol Sci. 2022. PMID: 35163689 Free PMC article.
-
Histone demethylase KDM5B licenses macrophage-mediated inflammatory responses by repressing Nfkbia transcription.Cell Death Differ. 2023 May;30(5):1279-1292. doi: 10.1038/s41418-023-01136-x. Epub 2023 Mar 13. Cell Death Differ. 2023. PMID: 36914768 Free PMC article.
-
Psoriasis and Seasonality: Exploring the Genetic and Epigenetic Interactions.Int J Mol Sci. 2024 Oct 30;25(21):11670. doi: 10.3390/ijms252111670. Int J Mol Sci. 2024. PMID: 39519223 Free PMC article. Review.
-
The Molecular Pathophysiology of Psoriatic Arthritis-The Complex Interplay Between Genetic Predisposition, Epigenetics Factors, and the Microbiome.Front Mol Biosci. 2021 Apr 1;8:662047. doi: 10.3389/fmolb.2021.662047. eCollection 2021. Front Mol Biosci. 2021. PMID: 33869291 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous