Dataset Information

Skin Surface Protein Detection by Transdermal Analysis Patches in Pediatric Psoriasis.

ABSTRACT:

Introduction

Transdermal analysis patches (TAPs) noninvasively measure soluble proteins in the stratum corneum. Ultimately, such local protein profiles could benefit the search for biomarkers to improve personalized treatment in psoriasis. This study aimed to explore the patient friendliness and protein detection by TAP in pediatric psoriasis in daily clinical practice.

Methods

In this observational study, TAPs measuring CXC chemokine ligand (CXCL)-1/2, CC chemokine ligand (CCL)-27, interleukin (IL)-1RA, IL-23, IL-1α, IL-8, IL-4, IL-22, IL-17A, vascular endothelial growth factor (VEGF), human beta-defensin (hBD)-2, hBD-1, and kallikrein-related peptidase (KLK)-5 were applied on lesional, peri-lesional, and non-lesional skin sites of psoriasis patients aged >5 to <18 years. Discomfort during TAP removal as an indicator for patient friendliness was assessed by visual analogue scale (VAS; range 0-10).

Results

Thirty-two patients (median age 14.0 years) were included, of which 19 were treated with solely topical agents and 13 with systemic treatment. The median VAS of discomfort during TAP removal was 1.0 (interquartile range 1.0). Significantly higher levels in lesional versus non-lesional skin were found for IL-1RA, VEGF, CXCL-1/2, hBD-2, and IL-8, whereas lower levels were found for IL-1α. Skin surface proteins were measured in both treatment groups, with significant higher lesional levels of KLK-5, IL-1RA, hBD-2, IL-1α, IL-23, and CCL-27 in the systemic treatment group.

Conclusion

The TAP platform holds the potential for patient-friendly and noninvasive monitoring of skin-derived proteins in pediatric psoriasis patients in daily clinical practice.

SUBMITTER: Schaap MJ

PROVIDER: S-EPMC8491489 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Adhesive transdermal delivery devices (patches) are the latest advancement in the delivery of micronutrients. A common challenge in this mode of delivery includes surpassing the physical barrier of the skin, while the use of microneedle (MN) arrays, or pretreatment of the skin with MNs can be used for a more successful outcome. Limited evidence from human non-randomized trials point to a sub-optimal delivery of iron through skin patches, although no MNs were used in those trials. Moreover, the use of patches proved inefficient in reducing the prevalence of micronutrient deficiencies in post-bariatric surgery patients. The delivery of minerals was tested in animals using reservoir-type patches, gel/foam patches, MNs and iontophoresis. Results from these studies indicate a possible interplay between the dietary manipulation of mineral intake and the trandermal delivery through patches, as reduced, or regular dietary intake seems to increase absorption of the delivered mineral. Moreover, intervention duration could be an additional factor affecting absorption. Possible adverse events from animal studies include redness or decolorization of skin. In vitro and ex vivo studies revealed an increase in vitamin K, vitamin D and iron delivery, however a variety of methodological discrepancies are apparent in these studies, including the models used, the length of the MNs, the duration of application, temperature control and total micronutrient load in the patches. Data indicate that pre-treating the skin with MNs might enhance delivery; however, a source of variability in the observed effectiveness might include the different molecular weights of the nutrients used, skin factors, the ideal tip radius and MN wall thickness. Non-human studies indicate a potential benefit in combining MN with iontophoresis. Presently, the transdermal delivery seems promising with regard to nutritional supplementation, however limited evidence exists for its efficacy in humans. Future research should aim to control for both intervention duration, possible deficiency status and for the dietary intake of participants.

Project description:Herein we demonstrate the efficacy of an unbiased proteomics screening approach for studying protein expression changes in the KC-Tie2 psoriasis mouse model, identifying multiple protein expression changes in the mouse and validating these changes in human psoriasis. KC-Tie2 mouse skin samples (n=3) were compared with littermate controls (n=3) using gel-based fractionation followed by label-free protein expression analysis. 5482 peptides mapping to 1281 proteins were identified and quantitated: 105 proteins exhibited fold-changes ≥2.0 including: stefin A1 (average fold change of 342.4 and an average P = 0.0082; cystatin A, human orthologue); slc25a5 (average fold change of 46.2 and an average P = 0.0318); serpinb3b (average fold change of 35.6 and an average P = 0.0345; serpinB1, human orthologue); and kallikrein related peptidase 6 (average fold change of 4.7 and an average P = 0.2474; KLK6). We independently confirmed mouse gene expression-based increases of selected genes including serpinb3b (17.4-fold, P < 0.0001), KLK6 (9.0-fold, P = 0.002), stefin A1 (7.3-fold; P < 0.001) and slc25A5 (1.5-fold; P = 0.05) using qRT-PCR on a second cohort of animals (n=8). Parallel LC/MS/MS analyses on these same samples verified protein-level increases of 1.3-fold (slc25a5; P < 0.05), 29,000-fold (stefinA1; P < 0.01), 322-fold (KLK6; P < 0.0001) between KC-Tie2 and control mice. To underscore the utility and translatability of our combined approach, we analyzed gene and protein expression levels in psoriasis patient skin and primary keratinocytes vs. healthy controls. Increases in gene expression for slc25a5 (1.8-fold), cystatin A (3.0-fold), KLK6 (5.8-fold) and serpinB1 (76-fold; all P < 0.05) were observed between healthy controls and involved lesional psoriasis skin and primary psoriasis keratinocytes. Moreover slc25a5, cystatin A, KLK6 and serpinB1 protein were all increased in lesional psoriasis skin compared to normal skin. These results highlight the usefulness of preclinical disease models using readily-available mouse skin and demonstrate the utility of proteomic approaches for identifying novel peptides/proteins that are differentially regulated in psoriasis that could serve as sources of auto-antigens or provide novel therapeutic targets for the development of new anti-psoriatic treatments.