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Journal of Allergy and Clinical Immunology

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Skin TARC/CCL17 increase precedes the development of childhood atopic dermatitis - 05/06/23

Doi : 10.1016/j.jaci.2022.11.023 
Anne-Sofie Halling, MD a, b, Maria Rasmussen Rinnov, MD b, c, Iben Frier Ruge, MD a, b, Trine Gerner, MD, PhD b, Nina Haarup Ravn, MD b, Mette Hjorslev Knudgaard, MD b, Simon Trautner, MD, PhD c, Nikolai Loft, MD, PhD b, Lone Skov, MD, PhD, DmSci b, Simon F. Thomsen, MD, PhD, DmSci a, Alexander Egeberg, MD, PhD, DmSci a, Emma Guttman-Yassky, MD, PhD d, Aske L.L. Rosted, BSc e, Troels Petersen, PhD e, Ivone Jakasa, PhD f, Sanja Kezic, PhD g, Jacob P. Thyssen, MD, PhD, DmSci a, ⁎
a Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark 
c Department of Neonatology, Rigshospitalet, University of Copenhagen, Denmark 
e Niels Bohr Institute, University of Copenhagen, Denmark 
b Department of Dermatology and Allergy, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark 
d Department of Dermatology and the Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 
f Laboratory for Analytical Chemistry, Department of Chemistry and Biochemistry, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia 
g Amsterdam University Medical Center, University of Amsterdam, Coronel Institute of Occupational Health, Amsterdam Public Health Research Institute, Amsterdam, The Netherlands 

∗Corresponding author: Jacob P. Thyssen, MD, PhD, DmSci, Department of Dermatology and Venereology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, Building 4, DK-2400 Copenhagen N, Denmark.Department of Dermatology and VenereologyBispebjerg HospitalUniversity of CopenhagenBispebjerg Bakke 23Building 4DK-2400Copenhagen NDenmark

Abstract

Background

It is unknown whether skin biomarkers collected in infancy can predict the onset of atopic dermatitis (AD) and be used in future prevention trials to identify children at risk.

Objectives

This study sought to examine whether skin biomarkers can predict AD during the first 2 years of life.

Methods

This study enrolled 300 term and 150 preterm children at birth and followed for AD until the age of 2 years. Skin tape strips were collected at 0 to 3 days and 2 months of age and analyzed for selected immune and barrier biomarkers. Hazard ratio (HR) with 95% confidence interval (CI) using Cox regression was calculated for the risk of AD.

Results

The 2-year prevalence of AD was 34.6% (99 of 286) and 21.2% (25 of 118) among term and preterm children, respectively. Skin biomarkers collected at birth did not predict AD. Elevated thymus- and activation-regulated chemokine/C-C motif chemokine ligand 17 -levels collected at 2 months of age increased the overall risk of AD (HR: 2.11; 95% CI: 1.36-3.26; P = .0008) and moderate-to-severe AD (HR: 4.97; 95% CI: 2.09-11.80; P = .0003). IL-8 and IL-18 predicted moderate-to-severe AD. Low filaggrin degradation product levels increased the risk of AD (HR: 2.04; 95% CI: 1.32-3.15; P = .001). Elevated biomarker levels at 2 months predicted AD at other skin sites and many months after collection.

Conclusions

This study showed that noninvasively collected skin biomarkers of barrier and immune pathways can precede the onset of AD.

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Key words : Atopic dermatitis, birth cohort, immune biomarkers, predictive biomarkers, skin barrier biomarkers

Abbreviations used : AD, aHR, CI, CTACK, EASI, HR, IQR, SC, TARC/CCL17, TEWL, UCA


Plan


 The study received financial support from The Leo Foundation, The Lundbeck Foundation, The Novo Nordisk Foundation, Aage Bangs fond, Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, and Herlev and Gentofte Hospital Research Foundation. The study was conducted independent of these, and they had no influence on study design or data analysis.
 Disclosure of potential conflict of interest: A.-S. Halling reports grants from Herlev and Gentofte Hospital Research Foundation, Kgl Hofbundtmager Aage Bangs Foundation, and CAG-Allergy during the conduct of the study. Outside the submitted work, A.-S. Halling has been a speaker for LEO Pharma and consultant for Coloplast. Outside the submitted work, S.F. Thomsen has been a speaker for or served on advisory boards for Sanofi, AbbVie, LEO Pharma, Pfizer, Eli Lilly, Novartis, UCB Pharma, Almirall, and Janssen Pharmaceuticals; has received research support from Sanofi, AbbVie, LEO Pharma, Novartis, UCB Pharma, and Janssen Pharmaceuticals. Outside the submitted work, N. Loft has been a speaker for Eli Lilly and Janssen Cilag. J.P. Thyssen reports grants from the Leo Foundation, the Novo Nordisk Foundation, the Lundbeck Foundation; and grants from Savværksejer Jeppe Juhl og hustru Ovita Juhls Mindelegat, during the conduct of the study. Outside of this study, J.P. Thyssen has served as an advisor for AbbVie, Almirall, Arena Pharmaceuticals, Coloplast, OM Pharma, Aslan Pharmaceuticals, Union Therapeutics, Eli Lilly and Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and served as a speaker for AbbVie, Almirall, Eli Lilly and Co, LEO Pharma, Pfizer, Regeneron, and Sanofi-Genzyme; and received research grants from Pfizer, Regeneron, and Sanofi-Genzyme. Outside of the submitted work, A. Egeberg has received research funding from Pfizer, Eli Lilly, Novartis, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, the Danish National Psoriasis Foundation, the Simon Spies Foundation, and the Kgl Hofbundtmager Aage Bang Foundation; and honoraria as consultant and/or speaker from AbbVie, Almirall, LEO Pharma, Zuellig Pharma Ltd, Galápagos NV, Sun Pharmaceuticals, Samsung Bioepis Co, Ltd, Pfizer, Eli Lilly and Co, Novartis, Union Therapeutics, Galderma, Dermavant, UCB, Mylan, Bristol-Myers Squibb, and Janssen Pharmaceuticals. T. Gerner reports grants from Herlev and Gentofte Hospital Research Foundation and Kgl Hofbundtmager Aage Bangs Foundation during the conduct of the study. M.R. Rinnov reports grants from Herlev and Gentofte Hospital Research Foundation and Kgl Hoftbundsmager Aage Bangs Foundation during the conduct of the study. L. Skov has served as an advisor for AbbVie, Novartis, Almirall, LEO Pharma, Pfizer, Bristol-Myers Squibb, Boehringer Ingelheim, UCB, Eli Lilly, and Sanofi-Genzyme; and served as a speaker for AbbVie, LEO Pharma, Pfizer, Novartis, AbbVie, and Sanofi-Genzyme; and received research grants from Leo Pharma, Janssen-Cilag, Bristol-Myers Squibb, UCB, and Sanofi-Genzyme. N.H. Ravn and M.H. Knudgaard report grants from Herlev and Gentofte Hospital Research Foundation, during the conduct of the study. E. Guttman-Yassky is an employee of Mount Sinai and outside the submitted work she has received research funding from Amgen, AnaptysBio, Asana Biosciences, AstraZeneca, Boehringer-Ingelheim, Cara Therapeutics, Celgene, Eli Lilly, Innovaderm, Kyowa Kirin, Leo Pharma, Novartis, Pfizer, and Regeneron Pharmaceuticals; and honoraria as consultant from AbbVie, Almirall, Amgen, Arena, Asana Biosciences, Aslan Pharmaceuticals, AstraZeneca, Boehringer-Ingelheim, Bristol-Meyers Squibb, Cara Therapeutics, Celgene, Connect Pharma, Eli Lilly, EMD Serono, Evidera, Galderma, Ichnos Sciences, Incyte, Janssen Biotech, Kyowa Kirin, Leo Pharma, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc, Sanofi, SATO Pharmaceutical, Siolta Therapeutics, Target Pharma Solutions, UCB, and Ventyx Biosciences. The rest of the authors declare that they have no relevant conflicts of interest.


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Vol 151 - N° 6

P. 1550 - juin 2023 Retour au numéro
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