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Published on: November 8, 2015
Early Proteomic Alterations in Non-segmental Vitiligo Skin Following Treatment with Topical Tacrolimus
Morten B Haulrig1,2,3, Sonja Kabatnik3,4, Lone Skov1,2
1Department of Dermatology and Allergy, Copenhagen University Hospital - Herlev and Gentofte Hospital, Hellerup, Denmark.
Introduction:
Vitiligo is a chronic depigmenting skin disease that can severely affect quality of life. First-line treatments include topical calcineurin inhibitors such as tacrolimus, but their molecular mechanisms of action in vitiligo remain incompletely understood. In this study, we investigated the early proteomic changes in patients with non-segmental vitiligo treated with topical tacrolimus.
Methods:
We included eight patients and collected 2-mm punch biopsies from untreated lesional skin (LS) and nonlesional skin (NLS), as well as from LS skin after 2 and 8 weeks of treatment. Samples were analyzed with mass spectrometry-based proteomics. We used a pairwise comparison between untreated LS and NLS, and linear mixed models to compare untreated LS and tacrolimus-treated LS.
Results:
In total, 4416 proteins were identified. Comparison between untreated LS and NLS revealed 32 differentially expressed proteins (DEPs; false discovery rate < 0.05), primarily associated with muscle contraction and melanocyte function. After 2 weeks of treatment, LS showed enrichment of 31 DEPs related to acute inflammatory responses and melanocyte adhesion, while LS treated for 8 weeks showed enrichment of 14 DEPs involved in melanogenesis, interferon-induced inflammation, and heat shock responses.
Conclusion:
This study characterizes the early proteomic response of the skin to tacrolimus treatment and offers insights into disease-associated proteins in vitiligo.
Insights
Topical tacrolimus treatment for vitiligo rapidly alters skin proteins involved in inflammation and melanocyte function. This study reveals early molecular changes, offering insights into vitiligo pathogenesis and treatment mechanisms.
Area of Science:
- Dermatology
- Proteomics
- Molecular Biology
Background:
- Vitiligo is a chronic skin depigmentation impacting quality of life.
- Topical calcineurin inhibitors like tacrolimus are first-line treatments, but their mechanisms are unclear.
- This study explores early proteomic changes in vitiligo patients treated with topical tacrolimus.
Purpose of the Study:
- To investigate the early molecular mechanisms of topical tacrolimus in non-segmental vitiligo.
- To identify proteomic alterations in lesional skin after tacrolimus treatment.
- To understand the protein changes associated with vitiligo and its treatment response.
Main Methods:
- Collected skin biopsies from vitiligo patients at baseline, 2 weeks, and 8 weeks of treatment.
- Utilized mass spectrometry-based proteomics to analyze protein expression.
- Compared protein profiles between lesional and nonlesional skin, and across treatment time points.
Main Results:
- Identified 4416 proteins, with 32 differentially expressed proteins (DEPs) between untreated lesional and nonlesional skin, linked to muscle contraction and melanocyte function.
- After 2 weeks of tacrolimus treatment, 31 DEPs related to inflammation and melanocyte adhesion were enriched.
- At 8 weeks, 14 DEPs involved in melanogenesis, interferon response, and heat shock were identified.
Conclusions:
- Characterized the early proteomic response to topical tacrolimus in vitiligo.
- Provided insights into disease-associated proteins and potential therapeutic targets.
- Highlighted the dynamic molecular changes occurring during vitiligo treatment.
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