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Transfer RNA-derived fragment tRF-28-QSZ34KRQ590K in plasma exosomes may be a potential biomarker for atopic dermatitis in pediatric patients.

ABSTRACT: Atopic dermatitis (AD) is a common chronic relapsing inflammatory disease. There is substantial evidence suggesting that noncoding RNAs have indispensable roles in the pathogenesis of AD. Exosomal transfer RNA-derived fragments (tRFs) have been identified as potential biomarkers for various disorders. However, the role of tRFs in AD has remained to be elucidated, which was thus the aim of the present study. Plasma samples from 23 pediatric patients with AD and 23 healthy controls were collected. Exosomes were successfully isolated from plasma according to the manufacturer's protocol. Small RNA sequencing was performed in 3 patients with AD and 3 controls, and 135 significantly differentially expressed plasma exosomal tRFs were identified, including 36 upregulated and 99 downregulated tRFs. Using the miRanda and RNAhybrid databases, 58,227 target genes of these 135 differentially expressed tRFs were predicted. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses suggested that these target genes of tRFs are involved in multiple functions and pathways associated with AD. Downregulation of tRF-28-QSZ34KRQ590K and tRF-33-Q99P9P9NH57SD3 were validated in 20 patients with AD and 20 controls by reverse transcription-quantitative PCR and tRF-28-QSZ34KRQ590K exhibited significance in the receiver operating characteristic curve analysis. The present study was the first to provide a tRF profile in AD and implied that plasma exosomal tRF-28-QSZ34KRQ590K may be a potential biomarker for pediatric patients with AD. The present study enhanced the understanding of the pathogenesis of AD and provided a novel marker for the diagnosis and targeted treatment of AD.

SUBMITTER: Meng L

PROVIDER: S-EPMC8005743 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThere is a paucity of data addressing the risk of cataract development in pediatric patients with atopic dermatitis (AD).ObjectiveTo investigate the association of AD with subsequent cataract development and cataract surgery in a Korean pediatric population.Design, setting, and participantsThis population-based retrospective longitudinal cohort study used nationally representative data from the Korean National Health Insurance Service database from 2002 to 2013. Incident AD cases, consisting of patients younger than 20 years with AD and severe AD and were matched to 4 controls each using propensity score derived from age, sex, residential area, and household income.Main outcomes and measuresIncidence probabilities of cataract development and cataract surgery between the AD group and controls were compared using Kaplan-Meier methods and log-rank tests. Cox proportional hazard models were fitted for cataract and cataract surgery to determine the risk factors in the matched cohort.ResultsOf 34 375 patients with incident AD (16 159 girls [47%]; mean [SD] age, 3.47 [4.96] years), there were 3734 severe AD cases (10.9%) with 137 500 matched controls. Development of cataracts was not different between the AD and control groups, (0.216% vs 0.227%; 95% CI, -0.041% to 0.063%; P = .32) or between the severe AD cohort and their controls (0.520% vs 0.276%; 95% CI, -0.073% to 0.561%; P = .06). Cataract surgery was performed more frequently in the AD cohort than in the control group (0.075% vs 0.041%; 95% CI, 0.017%-0.050%; P = .02) and in the severe AD cohort compared with their controls (0.221% vs 0.070%; 95% CI, 0.021%-0.279%; P = .03). Severe AD was associated with both development of cataract (adjusted hazard ratio, 1.94; 95% CI, 1.06-3.58, P = .03) and requirement for cataract surgery (adjusted hazard ratio, 5.48; 95% CI, 1.90-15.79, P = .002).Conclusions and relevanceAbsolute risk of cataract was rare, with or without AD, even after 10 years of observation. However, our results suggest that pediatric patients with AD have an increased risk for cataracts requiring surgery and that disease severity may increase the risk for cataract development and cataract surgery.

Project description:Bi-allelic mutations in the dedicator of cytokinesis 8 (DOCK8) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient (n = 10) and AD (n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls (n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenyalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.

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Transfer RNA-derived fragment tRF-28-QSZ34KRQ590K in plasma exosomes may be a potential biomarker for atopic dermatitis in pediatric patients.

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