Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: Implications for atopic dermatitis

Maeve A. McAleer, Ivone Jaska, Nidhin Raj, Colm P. F. O'Donnell, Majella E. Lane, Anthony V. Rawlings, Rainer Voegeli, William McLean, Sanja Kezic, Alan D. Irvine

Research output: Contribution to journalArticle

18 Citations (Scopus)
93 Downloads (Pure)

Abstract

Background: Filaggrin is central to the pathogenesis of atopic dermatitis (AD). The cheeks are a common initiation site of infantile AD. Regional and temporal expression of levels of filaggrin degradation products [natural moisturizing factors (NMFs)], activities of filaggrin-processing enzymes [bleomycin hydrolase (BH) and calpain-1 (C-1)] and plasmin, and corneocyte envelope (CE) maturity in early life are largely unknown. Objectives: We conducted a cross-sectional, observational study investigating regional and age-dependent variations in NMF levels, activity of proteases and CE maturity in stratum corneum (SC) from infants to determine whether these factors could explain the observed predilection sites for AD in early life. Methods: We measured NMF using a tape-stripping method at seven sites in the SC of 129 children (aged < 12 months to 72 months) and in three sites in 56 neonates and infants (< 48 h to 3 months). In 37 of these neonates and infants, corneocyte size, maturity, BH, C-1 and plasmin activities were determined. Results: NMF levels are low at birth and increase with age. Cheek SC, compared with elbow flexure and nasal tip, has the lowest NMF in the first year of life and is the slowest to reach stable levels. Cheek corneocytes remain immature. Plasmin, BH and C-1 activities are all elevated by 1 month of age in exposed cheek skin, but not in elbow skin. Conclusions: Regional and temporal differences in NMF levels, CE maturity and protease activities may explain the predilection for AD to affect the cheeks initially and are supportive of this site as key for allergen priming in early childhood. These observations will help design early intervention and treatment strategies for AD.

Original languageEnglish
Pages (from-to)431-441
Number of pages11
JournalBritish Journal of Dermatology
Volume179
Issue number2
Early online date25 Apr 2018
DOIs
Publication statusPublished - Aug 2018

Keywords

  • Stratum corneum
  • atopic dermatitis
  • epidermal barrier
  • allergen sensitization
  • cheeks
  • transepidermal water loss
  • natural moistu

Fingerprint Dive into the research topics of 'Early-life regional and temporal variation in filaggrin-derived natural moisturizing factor, filaggrin-processing enzyme activity, corneocyte phenotypes and plasmin activity: Implications for atopic dermatitis'. Together they form a unique fingerprint.

  • Cite this