Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence

Carolyn Lou, Nandita Mitra, Bradley Wubbenhorst, Kurt D'Andrea, Ole Hoffstad, Brian S. Kim, Albert Yan, Andrea L. Zaenglein, Zelma Chiesa Fuxench, Katherine L. Nathanson, David J. Margolis

Research output: Contribution to journalArticle

Abstract

Background: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. Objective: To fine map TSLP and evaluate associations with the onset and persistence of AD. Methods: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. Results: The minor variant frequency for rs1898671 was 23.5% (95% CI, 21.4%-25.8%). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95% CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95% CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95% CI, 1.34-2.75) than homozygotes (OR, 1.28; 95% CI, 0.61-2.70). Conclusion: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.

Original languageEnglish (US)
Pages (from-to)595-601.e1
JournalAnnals of Allergy, Asthma and Immunology
Volume123
Issue number6
DOIs
StatePublished - Dec 2019

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Atopic Dermatitis
Odds Ratio
Linkage Disequilibrium
thymic stromal lymphopoietin
High-Throughput Nucleotide Sequencing
Homozygote
Heterozygote
Skin Diseases
Genome
Databases
Skin

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pulmonary and Respiratory Medicine

Cite this

Lou, C., Mitra, N., Wubbenhorst, B., D'Andrea, K., Hoffstad, O., Kim, B. S., ... Margolis, D. J. (2019). Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence. Annals of Allergy, Asthma and Immunology, 123(6), 595-601.e1. https://doi.org/10.1016/j.anai.2019.08.018
Lou, Carolyn ; Mitra, Nandita ; Wubbenhorst, Bradley ; D'Andrea, Kurt ; Hoffstad, Ole ; Kim, Brian S. ; Yan, Albert ; Zaenglein, Andrea L. ; Fuxench, Zelma Chiesa ; Nathanson, Katherine L. ; Margolis, David J. / Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence. In: Annals of Allergy, Asthma and Immunology. 2019 ; Vol. 123, No. 6. pp. 595-601.e1.
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abstract = "Background: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. Objective: To fine map TSLP and evaluate associations with the onset and persistence of AD. Methods: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. Results: The minor variant frequency for rs1898671 was 23.5{\%} (95{\%} CI, 21.4{\%}-25.8{\%}). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95{\%} CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95{\%} CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95{\%} CI, 1.34-2.75) than homozygotes (OR, 1.28; 95{\%} CI, 0.61-2.70). Conclusion: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.",
author = "Carolyn Lou and Nandita Mitra and Bradley Wubbenhorst and Kurt D'Andrea and Ole Hoffstad and Kim, {Brian S.} and Albert Yan and Zaenglein, {Andrea L.} and Fuxench, {Zelma Chiesa} and Nathanson, {Katherine L.} and Margolis, {David J.}",
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Lou, C, Mitra, N, Wubbenhorst, B, D'Andrea, K, Hoffstad, O, Kim, BS, Yan, A, Zaenglein, AL, Fuxench, ZC, Nathanson, KL & Margolis, DJ 2019, 'Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence', Annals of Allergy, Asthma and Immunology, vol. 123, no. 6, pp. 595-601.e1. https://doi.org/10.1016/j.anai.2019.08.018

Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence. / Lou, Carolyn; Mitra, Nandita; Wubbenhorst, Bradley; D'Andrea, Kurt; Hoffstad, Ole; Kim, Brian S.; Yan, Albert; Zaenglein, Andrea L.; Fuxench, Zelma Chiesa; Nathanson, Katherine L.; Margolis, David J.

In: Annals of Allergy, Asthma and Immunology, Vol. 123, No. 6, 12.2019, p. 595-601.e1.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Association between fine mapping thymic stromal lymphopoietin and atopic dermatitis onset and persistence

AU - Lou, Carolyn

AU - Mitra, Nandita

AU - Wubbenhorst, Bradley

AU - D'Andrea, Kurt

AU - Hoffstad, Ole

AU - Kim, Brian S.

AU - Yan, Albert

AU - Zaenglein, Andrea L.

AU - Fuxench, Zelma Chiesa

AU - Nathanson, Katherine L.

AU - Margolis, David J.

PY - 2019/12

Y1 - 2019/12

N2 - Background: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. Objective: To fine map TSLP and evaluate associations with the onset and persistence of AD. Methods: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. Results: The minor variant frequency for rs1898671 was 23.5% (95% CI, 21.4%-25.8%). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95% CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95% CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95% CI, 1.34-2.75) than homozygotes (OR, 1.28; 95% CI, 0.61-2.70). Conclusion: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.

AB - Background: Atopic dermatitis (AD) is a common chronic relapsing skin disease. Genetic variants have been associated with skin barrier function and immune regulation. Thymic stromal lymphopoietin (TSLP), an immune regulator, has been previously associated with AD. Objective: To fine map TSLP and evaluate associations with the onset and persistence of AD. Methods: TSLP variation was determined using targeted massively parallel sequencing in a longitudinal cohort of children with AD. Evaluations included linkage disequilibrium and the persistence of AD for as many as 10 years of follow-up. The association between the presence of AD and rs1898671 variation was evaluated in a second independent cohort. Results: The minor variant frequency for rs1898671 was 23.5% (95% CI, 21.4%-25.8%). This variant was not in linkage disequilibrium with other TSLP variants in the longitudinal cohort (n = 741). White children with AD were less likely to have rs1898671 variant (odds ratio [OR], 1.41; 95% CI, 1.20-1.66) than Genome Aggregation Database controls. Children with AD and the rs1898671 variant during follow-up were more likely to have remission than children who were wild type for rs1898671 (OR, 1.56; 95% CI, 1.26-1.91). In the second cohort (n = 585), the rs1898671 variant was less prevalent in those with AD than those without. The protective effect was greater in rs1898671 heterozygotes (OR, 1.91; 95% CI, 1.34-2.75) than homozygotes (OR, 1.28; 95% CI, 0.61-2.70). Conclusion: TSLP and specifically rs1898671 are important in the pathogenesis of AD and could represent a potential clinical target for the development of therapies to treat individuals with AD.

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