Dataset Information

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

ABSTRACT: BACKGROUND:Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies. OBJECTIVE:To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects. METHODS:Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines and T-cell infiltrates in the interstitial skin fluid. Potential biomarkers were first defined and later validated in separate study groups. RESULTS:In screening and validation, CD8+ T-cell number and C-X-C motif chemokine ligand (CXCL) 9 protein concentration were significantly elevated in active lesional compared to nonlesional skin. CXCL9 protein concentration achieved greater sensitivity and specificity by receiver operating characteristic analysis. Suction blistering also allowed for phenotyping of the T-cell infiltrate, which overwhelmingly expresses C-X-C motif chemokine receptor 3. LIMITATIONS:A small number of patients were enrolled for the study, and only a single patient was used to define the treatment response. CONCLUSION:Measuring CXCL9 directly in the skin might be effective in clinical trials as an early marker of treatment response. Additionally, use of the modified suction-blister technique supports investigation of inflammatory skin diseases using powerful tools like flow cytometry and protein quantification.

SUBMITTER: Strassner JP

PROVIDER: S-EPMC5392432 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

Strassner James P JP Rashighi Mehdi M Ahmed Refat Maggi M Richmond Jillian M JM Harris John E JE

Journal of the American Academy of Dermatology 20170301 5

<h4>Background</h4>Vitiligo is an autoimmune disease of the skin with limited treatment options; there is an urgent need to identify and validate biomarkers of disease activity to support vitiligo clinical studies.<h4>Objective</h4>To investigate potential biomarkers of disease activity directly in the skin of vitiligo subjects and healthy subjects.<h4>Methods</h4>Patient skin was sampled via a modified suction-blister technique, allowing for minimally invasive, objective assessment of cytokines ...[more]

PMID: 28259440

Similar Datasets

Project description:Vitiligo is an acquired depigmentation skin disease caused by immune-mediated death of melanocytes. The most common treatment for vitiligo is narrow band ultraviolet B phototherapy, which often is combined with topical therapies such as tacrolimus. However, patients' responses to these treatments show large variations. To date, the mechanism for this heterogeneity is unknown, and there are no molecular indicators that can predict an individual patient's response to therapy. The goal of this study is to identify clinical parameters and gene expression biomarkers associated with vitiligo response to therapy. Six patients with segmental vitiligo and 30 patients with non-segmental vitiligo underwent transcriptome sequencing of lesional and nonlesional skin at baseline before receiving combined UBUVB and tacrolimus therapy for 6 month, and were separated into good response and bad response groups based on target lesion achieving > 10% repigmentation or not. Our study revealed that treatment-responsive vitiligo lesions had significantly shorter disease duration compared with non-responsive vitiligo lesions (2.5 years vs 11.5 years, p=0.046, t-Test), while showing no significant differences in the age, gender, ethnicity, vitiligo subtype, or disease severity. Transcriptomic analyses identified a panel of 68 genes separating the good response from bad response lesions including upregulation of immune active genes, such as CXCL10, FCRL3, and TCR, Further, compared with vitiligo lesions with long disease duration, the lesions with short duration also have much higher level of expression of immune-active genes, including some (such as FCRL3 and TCR genes) that are associated with favorable therapeutic response. In conclusion, our study has identified clinical parameters such as short disease duration and a panel of immune active and other gene expression biomarkers that are associated with favorable response to immune suppressive NBUVB + tacrolimus therapy. These markers may be useful clinically for individualized therapeutic management of vitiligo patients in the future.

Project description:ObjectiveSkin inflammation heralds systemic disease in juvenile myositis, yet we lack an understanding of pathogenic mechanisms driving skin inflammation in this disease. We undertook this study to define cutaneous gene expression signatures in juvenile myositis and identify key genes and pathways that differentiate skin disease in juvenile myositis from childhood-onset systemic lupus erythematosus (SLE).MethodsWe used formalin-fixed paraffin-embedded skin biopsy samples from 15 patients with juvenile myositis (9 lesional, 6 nonlesional), 5 patients with childhood-onset SLE, and 8 controls to perform transcriptomic analysis and identify significantly differentially expressed genes (DEGs; q ≤ 5%) between patient groups. We used Ingenuity Pathway Analysis (IPA) to highlight enriched biologic pathways and validated DEGs by immunohistochemistry and quantitative real-time polymerase chain reaction.ResultsComparison of lesional juvenile myositis to control samples revealed 221 DEGs, with the majority of up-regulated genes representing interferon (IFN)-stimulated genes. CXCL10, CXCL9, and IFI44L represented the top 3 DEGs (fold change 23.2, 13.3, and 13.0, respectively; q < 0.0001). IPA revealed IFN signaling as the top canonical pathway. When compared to childhood-onset SLE, lesional juvenile myositis skin shared a similar gene expression pattern, with only 28 unique DEGs, including FBLN2, CHKA, and SLURP1. Notably, patients with juvenile myositis who were positive for nuclear matrix protein 2 (NXP-2) autoantibodies exhibited the strongest IFN signature and also demonstrated the most extensive Mx-1 immunostaining, both in keratinocytes and perivascular regions.ConclusionLesional juvenile myositis skin demonstrates a striking IFN signature similar to that previously reported in juvenile myositis muscle and peripheral blood. Further investigation into the association of a higher IFN score with NXP-2 autoantibodies may provide insight into disease endotypes and pathogenesis.

Dataset Information

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

Publications

Suction blistering the lesional skin of vitiligo patients reveals useful biomarkers of disease activity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets