Abstract
Background: Mutations in the filaggrin gene (FLG) affect epidermal barrier function and increase the risk of atopic dermatitis (AD). We hypothesized that FLG mutations affect immune cell composition in a general pediatric population. Therefore, we investigated whether school-aged children with and without FLG mutations have differences in T- and B-cell subsets. Methods: This study was embedded in a population-based prospective cohort study, the Generation R Study, and included 523 children of European genetic ancestry aged 10 years. The most common FLG mutations in the European population (R501X, S1085CfsX36, R2447X, and S3247X) were genotyped. Additionally, 11-color flow cytometry was performed on peripheral blood samples to determine helper T (Th), regulatory T (Treg), and CD27+ and CD27- memory B cells. Subset analysis was performed in 358 non-AD and 102 AD cases, assessed by parental questionnaires. Results: FLG mutations were observed in 8.4% of the total population and in 15.7% of the AD cases. Children with any FLG mutation had higher Th22 cell numbers compared to FLG wild-type children in the general and non-AD population. Children with and without FLG mutations had no difference in Th1, Th2, Th17, Treg, or memory B-cell numbers. Furthermore, in children with AD, FLG mutation carriership was not associated with differences in T- and B-cell subsets. Conclusions: School-aged children of a general population with FLG mutations have higher Th22 cell numbers, which reflects the immunological response to the skin barrier dysfunction. FLG mutations did not otherwise affect the composition of the adaptive immunity in this general pediatric population.
| Original language | English |
|---|---|
| Pages (from-to) | 1360-1368 |
| Number of pages | 9 |
| Journal | Pediatric Allergy and Immunology |
| Volume | 32 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 14 Mar 2021 |
Bibliographical note
Funding Information:This article was funded by LIFECYCLE, grant agreement No 733206, 2016; EUCAN-Connect grant agreement No 824989; ATHLETE, grant agreement No 874583; Australian National Health and Medical Research Council, Grant/Award Number: 1117687; European Union's Horizon 2020 research and innovation programme, Grant/Award Number: 733206; European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Grant/Award Number: 696295. The Department of Dermatology of the Erasmus MC University Medical Center Rotterdam received an unrestricted grant from Micreos Human Health, The Netherlands. We gratefully acknowledge the contribution of children and parents, general practitioners, hospitals and midwives, and pharmacies in pharmacies in Rotterdam. We thank the following organizations for financially supporting our work: LIFECYCLE, grant agreement no 733206, 2016; EUCAN-Connect grant agreement no 824989; ATHLETE, grant agreement no 874583; Australian National Health and Medical Research Council, Grant/Award Number: 1117687; European Union's Horizon 2020 research and innovation program, Grant/Award Number: 733206; European Union's Horizon 2020 co-funded program ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL), Grant/Award Number: 696295. The Department of Dermatology of the Erasmus MC University Medical Center Rotterdam received an unrestricted grant from Micreos Human Health, the Netherlands. The funders had no role in the design or conduct of the study; the collection of the data and analyses; the interpretation of data; the preparation and review or approval of the manuscript; or the decision to submit the manuscript.
Publisher Copyright:
© 2021 The Authors. Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.