In vivo quantitative analysis of advanced glycation end products in atopic dermatitis—Possible culprit for the comorbidities?

Abstract

Advanced glycation end products (AGEs) interact with the membrane‐bound receptor for AGEs (RAGE), consequently amplifying the inflammatory response. Soluble receptor for AGE (sRAGE) and endogenous secretory RAGE (esRAGE) act as decoys for AGE and competitively sequester RAGE ligands, thereby serving a cytoprotective role. Our objective was to investigate AGE expression and their receptors in the serum and skin of patients with atopic dermatitis (AD). In this case‐control study, the levels of AGE, sRAGE and esRAGE were measured in the blood samples and corneocytes of 29 adult patients with AD and 12 healthy controls by ELISA. Corneocyte AGE levels increased in the AD group (P = .002). Higher corneocyte AGE levels were observed in the severe AD than in the milder form of AD. No significant difference in serum AGE level was observed in patients with AD and healthy controls. Serum sRAGE markedly decreased in patients with AD (P = .007) and serum esRAGE followed a similar trend. In conclusion, dermal accumulation of AGE in AD may have a role in fuelling skin inflammation. The potential after‐effects of reduced neutralizer on systemic risk need further evaluation.

Post-Translational Modifications in Atopic Dermatitis: Current Research and Clinical Relevance

“…A previous study found that urinary pentosidine, an AGE formed by sequential glycation and oxidation, tends to be higher in AD patients with acute exacerbation ( Tsukahara et al, 2003 ). Correspondingly, the level of AGEs in corneocytes from AD patients is increasing along with lesion severity ( Hong et al, 2020 ). Additionally, an increasing expression of receptor for AGEs (RAGE) is observed in AD-like mouse models, which results in the release of pro-inflammatory cytokines ( Dumitriu et al, 2005 ; Karuppagounder et al, 2015 ; Wang et al, 2018 ).…”

“…We emphasized that aberrant PTMs could trigger complex cascades of multi-cellular and multi-factorial pathways in AD pathophysiology, and the diagnostic and prognostic significance of PTMs should however be mentioned. Currently, dermal AGEs and urinary pentosidine have been used as biomarkers for early detection and prognosis estimation in AD ( Tsukahara et al, 2003 ; Hong et al, 2020 ). With the introduction of skin autofluorescence in AGEs measurement, it raises the possibility of non-invasive tools in assessing both the disease severity and the comorbidity risks in the future ( Ying et al, 2021 ).…”

Recent progress at the psoriasis and atopic dermatitis research front: An experimental dermatology perspective

“…AGE level is greatly elevated during ageing and in poorly controlled diabetes, cardiovascular diseases and atherosclerosis 40,42 . Recent studies, including one published in EXD, have found that AGE levels are also increased in the skin and blood of patients with PSO or AD 41,43 . AGEs may activate membrane receptors of epithelial cells and immune cells, promoting the production of proinflammatory cytokines and reactive oxygen species and the activation of metalloproteases 41 .…”

Glyoxalase System in the Progression of Skin Aging and Skin Malignancies

“…However, RNA expression profiling of uninvolved and lesion skin from psoriasis patients showed decreased expression of Glo1 [60]. Hong et al reported that the skin of patients with atopic dermatitis (AD) has a higher expression of AGEs in corneocytes than in normal healthy controls, and the accumulation of dermal AGEs in AD increases oxidative stress, causing skin inflammation [61]. AD is a chronic inflammation of the skin characterized by pruritus and eczema.…”