Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis

Abstract

Background Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. Objective To characterize the plasma inflammatory signature of CHE. Methods Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, clinical- and self-reported variables were performed. Results Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper cell (Th)2, Th1, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe, but not mild AD, displayed systemic inflammation. Th2 markers chemokine (C-C motif) ligand (CCL)17 and CCL13 were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. Conclusion Systemic Th2-driven inflammation is shared between very severe, CHE without AD and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Inflammatory plasma signature of chronic hand eczema: Associations with aetiological and clinical subtypes

“…The study was conducted within a large study investigating biomarkers of dermatitis (local ethics committee approval No. H‐16050507) 11,13,14 . A subsample of 51, adult, Danish, fair skinned patients with CHE, without concomitant AD, as well as 40 age and sex matched healthy controls were included in this study.…”

“…This information was confirmed by a second physician at inclusion where clinical severity and clinical CHE subtypes were also assessed. Inclusion and exclusion criteria have been previously described 11 …”

“…Plasma was retrieved, stored at −80°C and analysed by use of Olink Proseek® Multiplex Assay (Olink Bioscience) as previously described 11 . The panels inflammation, CVD II and CVD III, each measuring 92 proteins, were used.…”

“…Genotypes for mutations in filaggrin gene R501X, 2282del4, R2447X and S3247 were determined from genomic DNA extracted from whole blood as previously described 11 …”

“…Plasma collection is minimally invasive and can provide important information on systemic biomarkers, when coupled with broad proteomic approaches. We have recently shown that CHE leaves systemic traces, and that inflammatory plasma biomarkers are associated, and correlate, with the clinical disease severity of non‐AD CHE 11,12 . Whether different aetiological and clinical CHE subtypes leave specific systemic footprints remains unknown.…”