INTRODUCTION
Atopic dermatitis (AD) is a common inflammatory skin disease affecting
up to 10% of adults and 20% of children
worldwide.1,2 Our knowledge of AD pathomechanisms is
largely derived from molecular studies in skin biopsies that demonstrate
primarily Th2/Th22 inflammation with variable Th1/Th17 skewing, as well
as epidermal barrier dysregulation, including epidermal hyperplasia and
abnormalities in terminal differentiation, tight junctions, and lipid
biosynthesis/metabolism.3-12 While skin biopsies were
instrumental to deciphering disease characteristics, they are associated
with pain, scarring, and infection risk, restricting their use in
large-scale clinical trials and longitudinal studies, which are critical
for adults and even more in children.13-15 Tape-strips
are a minimally invasive, nonscarring approach to collect skin samples
to the level of the upper stratum granulosum.16 Recent
studies have demonstrated significant utility of tape-strips in
profiling AD skin in both adults and children,6,16-30and in monitoring disease activity in response to
treatment.31-34
Comprehensive molecular intra-patient comparison of tape-strips to
full-thickness biopsies is currently lacking. Moreover, there is no
detailed comparison of immune, barrier, and itch-related markers between
the two techniques. 16,35,36 Several studies described
differences between tape-strips and biopsies using a limited panel of
markers. Andersson et al. analyzed only 17 immune markers in AD skin and
noted that CCL17 and markers of innate immunity were significantly
up-regulated and correlated with disease activity in tape-strips but not
in same-cohort biopsies.36 Simonsen et al. assessed 10
cytokines in AD lesions and noted greater up-regulation in the innate
immunity marker IL-1B in tape-strips, while dysregulation of Th2 markers
and IFN-γ were only detected in biopsies.35 Of note,
this study measured mRNA expression in biopsies while proteomics was
performed in tape-strips. Kim et al. measured mRNA of 5 epidermal
differentiation markers in tape-strips, reporting positive correlations
with protein levels in biopsies.16 Utilizing RNAseq,
Sølberg et al. reported that structural genes like keratins were higher
in biopsies while immune markers IL-8 and IL-36A were higher in
tape-strips.18 Dyjack et al. analyzed tape-strips from
non-lesional AD skin, noting better representation of cornification
genes in tape-strips compared to biopsies.37 These
studies enzymatically separated the epidermis and dermis in biopsies,
potentially overlooking important pathogenic features within the entire
AD skin transcriptome.
Herein, we present a global RNA-seq intra-patient profiling of
tape-strips and whole-skin biopsies in moderate-to-severe AD as compared
to healthy subjects. Our data highlight features that are better
captured by tape-strips, including Th2 polarization, itch pathway
activation, and terminal differentiation impairment, whereas Th22
changes and epidermal hyperplasia are more pronounced in biopsies. These
findings suggest that tape-strips and biopsies each preferentially
detect unique disease characteristics, which should be considered when
selecting skin sampling approaches in clinical trials or longitudinal
studies.