Increased Th22 cell numbers in a general pediatric population with filaggrin haploinsufficiency: The Generation R Study

• Published in: Pediatric allergy and immunology Vol. 32; no. 6; pp. 1360 - 1368
• Main Authors: Looman, Kirsten I. M., Mierlo, Minke M. F., Zelm, Menno C., Hu, Chen, Duijts, Liesbeth, Jongste, Johan C., Nijsten, Tamar, Pardo, Luba M., Kiefte‐de Jong, Jessica C., Moll, Henriëtte A., Pasmans, Suzanne G. M. A., Riggioni, Carmen
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.08.2021; John Wiley and Sons Inc
• Subjects: Adaptive immunity; Atopic dermatitis; CD27 antigen; Children; Eczema; Filaggrin; Flow cytometry; Haploinsufficiency; Helper cells; IgE memory B cell; Immunological memory; Lymphocytes B; Lymphocytes T; Memory cells; Mutation; Original; Pediatrics; Peripheral blood; Population; Population studies; T helper cell; T regulatory cell; atopic dermatitis; T regulatory cell; IgE memory B cell; Filaggrin; T helper cell
• ISSN: 0905-6157; 1399-3038
• DOI: 10.1111/pai.13502

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.