Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis

Lam C. Tsoi, Elke Rodriguez, Frauke Degenhardt, Hansjörg Baurecht, Ulrike Wehkamp, Natalie Volks, Silke Szymczak, William R. Swindell, Mrinal K. Sarkar, Kalpana Raja, Shuai Shao, Matthew Patrick, Yilin Gao, Ranjitha Uppala, Bethany Elena Perez-White, Spiro Getsios, Paul W. Harms, Emanual Maverakis, James T. Elder, Andre Franke & 2 others Johann E. Gudjonsson*, Stephan Weidinger

*Corresponding author for this work

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.

Original languageEnglish (US)
Pages (from-to)1480-1489
Number of pages10
JournalJournal of Investigative Dermatology
Volume139
Issue number7
DOIs
StatePublished - Jul 1 2019

Fingerprint

Atopic Dermatitis
Psoriasis
Skin
RNA Sequence Analysis
RNA
Transcriptome
Genes
Long Noncoding RNA
Interleukin-13
Skin Diseases
Interleukin-4
Cytokines
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Tsoi, L. C., Rodriguez, E., Degenhardt, F., Baurecht, H., Wehkamp, U., Volks, N., ... Weidinger, S. (2019). Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. Journal of Investigative Dermatology, 139(7), 1480-1489. https://doi.org/10.1016/j.jid.2018.12.018
Tsoi, Lam C. ; Rodriguez, Elke ; Degenhardt, Frauke ; Baurecht, Hansjörg ; Wehkamp, Ulrike ; Volks, Natalie ; Szymczak, Silke ; Swindell, William R. ; Sarkar, Mrinal K. ; Raja, Kalpana ; Shao, Shuai ; Patrick, Matthew ; Gao, Yilin ; Uppala, Ranjitha ; Perez-White, Bethany Elena ; Getsios, Spiro ; Harms, Paul W. ; Maverakis, Emanual ; Elder, James T. ; Franke, Andre ; Gudjonsson, Johann E. ; Weidinger, Stephan. / Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. In: Journal of Investigative Dermatology. 2019 ; Vol. 139, No. 7. pp. 1480-1489.
@article{2a32f3eb830940449aa6c37ebd730594,
title = "Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis",
abstract = "Atopic dermatitis (AD) affects up to 20{\%} of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81{\%} of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.",
author = "Tsoi, {Lam C.} and Elke Rodriguez and Frauke Degenhardt and Hansj{\"o}rg Baurecht and Ulrike Wehkamp and Natalie Volks and Silke Szymczak and Swindell, {William R.} and Sarkar, {Mrinal K.} and Kalpana Raja and Shuai Shao and Matthew Patrick and Yilin Gao and Ranjitha Uppala and Perez-White, {Bethany Elena} and Spiro Getsios and Harms, {Paul W.} and Emanual Maverakis and Elder, {James T.} and Andre Franke and Gudjonsson, {Johann E.} and Stephan Weidinger",
year = "2019",
month = "7",
day = "1",
doi = "10.1016/j.jid.2018.12.018",
language = "English (US)",
volume = "139",
pages = "1480--1489",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "7",

}

Tsoi, LC, Rodriguez, E, Degenhardt, F, Baurecht, H, Wehkamp, U, Volks, N, Szymczak, S, Swindell, WR, Sarkar, MK, Raja, K, Shao, S, Patrick, M, Gao, Y, Uppala, R, Perez-White, BE, Getsios, S, Harms, PW, Maverakis, E, Elder, JT, Franke, A, Gudjonsson, JE & Weidinger, S 2019, 'Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis', Journal of Investigative Dermatology, vol. 139, no. 7, pp. 1480-1489. https://doi.org/10.1016/j.jid.2018.12.018

Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis. / Tsoi, Lam C.; Rodriguez, Elke; Degenhardt, Frauke; Baurecht, Hansjörg; Wehkamp, Ulrike; Volks, Natalie; Szymczak, Silke; Swindell, William R.; Sarkar, Mrinal K.; Raja, Kalpana; Shao, Shuai; Patrick, Matthew; Gao, Yilin; Uppala, Ranjitha; Perez-White, Bethany Elena; Getsios, Spiro; Harms, Paul W.; Maverakis, Emanual; Elder, James T.; Franke, Andre; Gudjonsson, Johann E.; Weidinger, Stephan.

In: Journal of Investigative Dermatology, Vol. 139, No. 7, 01.07.2019, p. 1480-1489.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Atopic Dermatitis Is an IL-13–Dominant Disease with Greater Molecular Heterogeneity Compared to Psoriasis

AU - Tsoi, Lam C.

AU - Rodriguez, Elke

AU - Degenhardt, Frauke

AU - Baurecht, Hansjörg

AU - Wehkamp, Ulrike

AU - Volks, Natalie

AU - Szymczak, Silke

AU - Swindell, William R.

AU - Sarkar, Mrinal K.

AU - Raja, Kalpana

AU - Shao, Shuai

AU - Patrick, Matthew

AU - Gao, Yilin

AU - Uppala, Ranjitha

AU - Perez-White, Bethany Elena

AU - Getsios, Spiro

AU - Harms, Paul W.

AU - Maverakis, Emanual

AU - Elder, James T.

AU - Franke, Andre

AU - Gudjonsson, Johann E.

AU - Weidinger, Stephan

PY - 2019/7/1

Y1 - 2019/7/1

N2 - Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.

AB - Atopic dermatitis (AD) affects up to 20% of children and adults worldwide. To gain a deeper understanding of the pathophysiology of AD, we conducted a large-scale transcriptomic study of AD with deeply sequenced RNA-sequencing samples using long (126-bp) paired-end reads. In addition to the comparisons against previous transcriptomic studies, we conducted in-depth analysis to obtain a high-resolution view of the global architecture of the AD transcriptome and contrasted it with that of psoriasis from the same cohort. By using 147 RNA samples in total, we found striking correlation between dysregulated genes in lesional psoriasis and lesional AD skin with 81% of AD dysregulated genes being shared with psoriasis. However, we described disease-specific molecular and cellular features, with AD skin showing dominance of IL-13 pathways, but with near undetectable IL-4 expression. We also demonstrated greater disease heterogeneity and larger proportion of dysregulated long noncoding RNAs in AD, and illustrated the translational impact, including skin-type classification and drug-target prediction. This study is by far the largest study comparing the AD and psoriasis transcriptomes using RNA sequencing and demonstrating the shared inflammatory components, as well as specific discordant cytokine signatures of these two skin diseases.

UR - http://www.scopus.com/inward/record.url?scp=85062674924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85062674924&partnerID=8YFLogxK

U2 - 10.1016/j.jid.2018.12.018

DO - 10.1016/j.jid.2018.12.018

M3 - Article

VL - 139

SP - 1480

EP - 1489

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 7

ER -