Highly accurate, noninvasive early identification of infants with a filaggrin loss-of-function mutation by in vivo Raman spectroscopy, followed from birth to 12 months

Background: Loss-of-function FLG mutation (FLGmut) carriers are at an increased risk of developing atopic dermatitis (AD), characterized by earlier onset and more severe disease. AD is driven by a complex interplay between skin barrier function, T_H2 and T_H2-dominant immune dysregulation, and dysbiosis. Results from the Short-Term Topical Application for Prevention of Atopic Dermatitis study suggest 2 early initiating AD pathogenetic pathways: an FLGmut-related skin barrier deficiency pathway and an immune function-related inflammatory pathway. The Short-Term Topical Application for Prevention of Atopic Dermatitis study suggested that early preventative intervention with specialized emollients for barrier function augmentation may benefit newborns with FLGmut. This requires early identification of FLGmut carriers, for which noninvasive Raman spectroscopic determination of natural moisturizing factor (NMF) levels in the stratum corneum of the thenar eminence provides a surrogate marker.

Objective: To identify strategies for early identification of infants with FLGmut.

Methods: FLG sequencing was performed on 253 infants, and NMF concentrations were measured in the stratum corneum of the palmar eminence (pSC-NMF) using noninvasive Raman spectroscopy at 6 time points after birth. Furthermore, the pSC-NMF concentrations were obtained from both parents of 150 infants.

Results: Babies are born with little to no NMF. In the first days after birth, NMF levels rapidly increase and 65% of newborns with FLG wild type already reach pSC-NMF concentrations, which excludes them as FLGmut carriers with high specificity. At 2 weeks of age, FLGmut carriers could be distinguished from newborns with FLG wild type with high sensitivity (97%) and specificity (97%). In addition, parent pSC-NMF concentrations offer the possibility to exclude their newborn as FLGmut carriers with high specificity.

Conclusion: Noninvasive Raman spectroscopy enables the accurate early identification of infants with FLGmut.