ArticleThe Journal of allergy and clinical immunology2022
Signaling sphingolipids are biomarkers for atopic dermatitis prone to disseminated viral infections.
Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 15 citations in OpenAlex.
- Stratum Corneum Ceramide Abnormalities in Atopic Dermatitis: Pathophysiology and Implications for Disease Management.The Journal of dermatology · 2026Review
- Uncovering pleiotropic loci linking keratoconus and allergic diseases through integrative genomic analyses.Scientific reports · 2026Article
- Atopic Dermatitis Complicated by Recurrent Eczema Herpeticum Is Characterized by Multiple, Concurrent Epidermal Inflammatory Endotypes.JID innovations : skin science from molecules to population health · 2024Article
- Circadian Rhythms in Skin Barrier Function in Atopic Dermatitis: A Pilot Study.Journal of biological rhythms · 2024Article
- Analytical challenges in omics research on asthma and allergy: A National Institute of Allergy and Infectious Diseases workshop.The Journal of allergy and clinical immunology · 2024Article
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundLife-threatening viral diseases such as eczema herpeticum (EH) and eczema vaccinatum (EV) occur in <5% of individuals with atopic dermatitis (AD). The diagnosis of AD, however, excludes all individuals with AD from smallpox vaccination.
objectivesWe sought to identify circulatory and skin lipid biomarkers associated with EH and EV.
methodsStratum corneum and plasma samples from 15 subjects with AD and a history of EH, 13 age- and gender-matched subjects with AD and without EH history, and 13 healthy nonatopic (NA) controls were analyzed by liquid chromatography tandem mass spectrometry for sphingolipid content. Sphingosine-1-phosphate (S1P) and ceramide levels were validated in plasma samples from the Atopic Dermatitis Vaccinia Network/Atopic Dermatitis Research Network repository (12 NA, 12 AD, 23 EH) and plasma from 7 subjects with EV and 7 matched subjects with AD. S1P lyase was downregulated in human primary keratinocytes to evaluate its effect on herpes simplex virus 1 (HSV-1) replication in vitro.
resultsThe stratum corneum of patients with EH demonstrated significantly higher levels of free sphingoid bases than those in patients who were NA, indicating enhanced sphingolipid turnover in keratinocytes (P < .05). Plasma from 2 independent cohorts of patients with EH had a significantly increased S1P/ceramide ratio in subjects with EH versus those with AD and or who were NA (P < .01). The S1P level in plasma from subjects with EV was twice the level in plasma from subjects with AD (mean = 1,533 vs 732 pmol/mL; P < .001). Downregulation of S1P lyase expression with silencing RNA led to an increased S1P level and doubled HSV-1 titer in keratinocytes.
conclusionsOur data point to long-term abnormalities in the S1P signaling system as a biomarker for previous disseminated viral diseases and a potential treatment target in recurring infections.
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