Dataset Information

Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis.

ABSTRACT: Atopic dermatitis (AD) is a common chronic illness of childhood.To evaluate the association between thymic stromal lymphopoietin (TSLP) variation and the persistence of skin symptoms of AD.A prospective cohort study was conducted in the general community. Participants included 796 children enrolled in the Pediatric Eczema Elective Registry. EXPOSURE Evaluation of TSLP variation.Self-reported outcome of whether a child's skin had no symptoms of AD and required no medications for 6 months at 6-month intervals.We evaluated 14 variants of TSLP. The variant rs1898671 was significantly associated with the outcome in white children (P =?.01). As measured by overlapping CIs, similar odds ratios (ORs) were noted among whites (OR, 1.72; 95% CI, 1.11-2.66) and African Americans (1.33; 0.52-3.45). Further within the subcohort of individuals with a filaggrin protein (FLG) loss-of-function mutation, those with TSLP variation were more likely to have less-persistent disease (OR, 4.92; 95% CI, 2.04-11.86).The TSLP variation is associated with less persistent AD. Therefore, TSLP may be a potential therapeutic target for the treatment of AD, especially in individuals with diminished barrier function due to FLG mutations. This is an attractive hypothesis that can be tested in clinical trials.

SUBMITTER: Margolis DJ

PROVIDER: S-EPMC4414492 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature

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Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis.

Margolis David J DJ Kim Brian B Apter Andrea J AJ Gupta Jayanta J Hoffstad Ole O Papadopoulos Maryte M Mitra Nandita N

JAMA dermatology 20140301 3

<h4>Importance</h4>Atopic dermatitis (AD) is a common chronic illness of childhood.<h4>Objective</h4>To evaluate the association between thymic stromal lymphopoietin (TSLP) variation and the persistence of skin symptoms of AD.<h4>Design, setting, and participants</h4>A prospective cohort study was conducted in the general community. Participants included 796 children enrolled in the Pediatric Eczema Elective Registry. EXPOSURE Evaluation of TSLP variation.<h4>Main outcomes and measures</h4>Self- ...[more]

PMID: 24401911

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Project description:Importance:Atopic dermatitis (AD) is a common chronic illness that has been associated with variation in the filaggrin gene (FLG). Four variants are most often evaluated. Objectives:To comprehensively describe and compare results from targeted sequencing of FLG loss-of-function (LoF) variants in children of African and European ancestry and the association of these variants with onset and persistence of AD. Design, Setting, and Participants:This prospective US cohort study assessed the genetic subcohort of the Pediatric Eczema Elective Registry (PEER). Children with mild to moderate AD were included in the analysis. Massively parallel sequencing (MPS) was used to focus on FLG LoF variation in white and African American children. Patients were enrolled from June 2005 through July 2017. Data were analyzed from January 25 through May 10, 2019. Main Outcomes and Measures:Associations of FLG LoF variation with white and African American ancestry and with the risk and persistence of AD. Results:A total of 741 children were included in the analysis (394 [53.2%] female and 347 [46.8%] male; mean [SD] age at onset, 1.97 [2.72] years); of these, 394 (53.2%) were white, 326 (44.0%) were African American, and 21 (2.8%) were of other ancestries. Using MPS technology, 23 FLG LoF variants were found in children with AD. The prevalence of FLG LoF variants was 177 participants (23.9%) in the full cohort, 124 white participants (31.5%), and 50 African American participants (15.3%). The odds ratio for carrying any FLG LoF variant in a white child compared with an African American child with AD was 2.44 (95% CI, 1.76-3.39). Some FLG LoF variants are only found in children of a specific ancestry (eg, p.S3316* and p.R826* were not seen in white patients). Children with an FLG LoF were more likely to have persistent AD (odds ratio, 0.67; 95% CI, 0.56-0.80). Conclusions and Relevance:The FLG LoF variants in a US cohort of children with mild to moderate AD differ significantly by race and their association with the persistence of AD. Conventional testing of the 4 frequently evaluated variants is inadequate. Any planned genetic diagnostic test for AD based on FLG LoF variants must be inclusive and not rely on the most frequently studied variants.

Dataset Information

Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis.

Publications

Thymic stromal lymphopoietin variation, filaggrin loss of function, and the persistence of atopic dermatitis.

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