Volume 187, Issue S1 p. 14
Abstract
Free Access

O07: Carbonylated proteins as markers of oxidative stress and their association with filaggrin genotype in atopic eczema

First published: 05 July 2022

Soha Tawfik,1,2 Krishanu Baruah,1 Aaron Hughes,1,3 Bjorn Thomas,1,3 Ryan O-Shaughnessy1 and Edel O’ Toole1,3

1Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK; 2Department of Dermatology, Venereology and Andrology, Faculty of Medicine, Alexandria University, Alexandria, Egypt; and 3The Royal London Hospital, Barts Health NHS Trust, London, UK

Oxidative stress has a major role in atopic eczema (AE). It results mainly from constant skin exposure to environmental stimulants such as ultraviolet light and pollutants. Carbonylated proteins (CPs) are irreversible aldehyde and ketone groups generated on protein side chains when oxidized. It has been shown that CP levels are higher in dry skin and AE skin lesions. Skin tape stripping (STS) is a relatively fast and simple technique compared with skin biopsy, from which protein can be extracted. The aim of this study was to evaluate CPs, filaggrin (FLG) and cytokeratin 10 (CK10) expression in skin tape strips of Bangladeshi patients with AE and normal controls by Western blotting. A secondary aim was to correlate protein expression with the FLG genotype status of each patient. As part of an East London research study, 33 patients with AE and nine normal controls of Bangladeshi ancestry, aged 0–30 years, were recruited. Buccal swabs were taken for DNA extraction and STS (nine tapes) were harvested from a nonlesional skin site on the volar aspect of the arm for protein extraction. Spearman correlation rho (ρ) was used for bivariate correlation. A two-sided unpaired Wilcoxon test was used for two-group comparisons. Kruskal–Wallis test and post hoc Wilcoxon signed rank pairwise tests were used to compare variables with more than two groups. There was no significant difference in FLG dimer, CK10 and CP expression levels between patients and controls (P = 0.378, P = 0.678 and P = 1.0, respectively). The number of FLG mutations correlated positively and significantly with CP expression level (ρ = 0.44, P = 0.01). For FLG mutation status, there were three groups (wildtype, n = 15; heterozygous, n = 9; compound heterozygous or homozygous, n = 9). There was no significant difference in harvested protein concentration between groups (P = 0.23). There was significantly higher median FLG dimer and CK10 expression in the compound heterozygotes/homozygous group compared with the heterozygous group (P = 0.054 and P = 0.023, respectively). There was a significant difference in CP expression levels between the three groups (P = 0.039), but post hoc testing showed no significance that might be related to the small sample size within each group. CPs, which represent a general oxidative marker in the skin, were significantly correlated with the number of FLG mutations. This suggests that carrying more than one mutation might be associated with more inducible oxidative stress by environmental stimuli in patients with AE. Strikingly, FLG dimer was highly expressed in patients carrying more than one mutation, confirming the complex multifactorial mechanism controlling barrier protein expression in AE.

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