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Unraveling heterogeneity in pediatric atopic dermatitis: Identification of serum biomarker based patient clusters - 05/01/22

Doi : 10.1016/j.jaci.2021.06.029 
Daphne S. Bakker, MD a, b, Marlies de Graaf, MD, PhD a, Stefan Nierkens, PhD b, Eveline M. Delemarre, MD, PhD b, Edward Knol, PhD b, Femke van Wijk, PhD b, Marjolein S. de Bruin-Weller, MD, PhD a, Julia Drylewicz, PhD b, , Judith L. Thijs, MD, PhD a,
a National Expertise Center for Atopic Dermatitis, Department of Dermatology and Allergology, University Medical Center Utrecht, Utrecht, The Netherlands 
b Center for Translational Immunology, University Medical Center Utrecht, Utrecht, The Netherlands 

Corresponding author: Judith Thijs, MD, University Medical Centre Utrecht, Department of Dermatology, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.University Medical Centre UtrechtDepartment of DermatologyHeidelberglaan 100UtrechtThe Netherlands3584 CX

Abstract

Background

Increasing evidence shows that pediatric atopic dermatitis (AD) differs from adult AD on a biologic level. Broad biomarker profiling across a wide range of ages of pediatric patients with AD is lacking.

Objective

Our aim was to identify serum biomarker profiles in children with AD aged 0 to 17 years and compare these profiles with those previously found in adults with AD.

Methods

Luminex multiplex immunoassays were used to measure 145 biomarkers in serum from 240 children with AD (aged 0-17 years). Principal components analysis followed by unsupervised k-means clustering were performed to identify patient clusters. Patients were stratified into age groups (0-4 years, 5-11 years, and 12-17 years) to assess association between age and cluster membership.

Results

Children aged 0 to 4 years had the highest levels of TH1 cell–skewing markers and lowest levels of TH17 cell–related markers. TH2 cell–related markers did not differ significantly between age groups. Similar to the pattern in adults, cluster analysis identified 4 distinct pediatric patient clusters (TH2 cell/retinol–dominant, skin-homing–dominant, TH1 cell/TH2 cell/TH17 cell/IL-1–dominant, and TH1 cell/IL-1/eosinophil–inferior clusters). Only the TH1 cell/TH2 cell/TH17 cell/IL-1–dominant cluster resembled 1 of the previously identified adult clusters. Although no association with age or age of onset seemed to be found, disease severity was significantly associated with the skin-homing–dominant cluster.

Conclusion

Four distinct patient clusters based on serum biomarker profiles could be identified in a large cohort of pediatric patients with AD, of which 1 was similar to previously identified adult clusters. The identification of endotypes driven by distinct underlying immunopathologic pathways might be useful to define pediatric patients with AD who are at risk of persistent disease and may necessitate different targeted treatment approaches.

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Key words : Atopic dermatitis, pediatric, biomarkers, endotypes, personalized medicine, principal components analysis, cluster analysis

Abbreviations used : AD, CCL, CTACK, CXCL, EASI, MCP-1, MDC, MMP, PARC, RBP4, TARC, TWEAK


Plan


 Supported by Regeneron and Sanofi Genzyme Pharmaceuticals, Inc.
 Disclosure of potential conflict of interest: D. Bakker, E. Knol, and J. Thijs have been speakers for Sanofi Genzyme. M. de Graaf has been the principal investigator and an advisory board member for Sanofi Genzyme and Regeneron Pharmaceuticals, Inc, and an advisory board member for Eli Lilly. M. De Bruin-Weller has been a consultant, advisory board member, and/or speaker for AbbVie, Almirall, Eli Lilly, Galderma, Janssen, Leo Pharma, Pfizer, Regeneron, Sanofi-Genzyme, and UCB. The rest of the authors declare that they have no relevant conflicts of interest.


© 2021  The Authors. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 149 - N° 1

P. 125-134 - janvier 2022 Retour au numéro
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