TOPLINE:

A pilot study evaluating minimally invasive tape-strip RNA sequencing found shared upregulation of Th17/Th22 immune markers and increased cornified envelope/epidermal differentiation complex (EDC) gene expression across all orphan ichthyosis subtypes, including Netherton syndrome, congenital ichthyosiform erythroderma, lamellar ichthyosis, and epidermolytic ichthyosis.

METHODOLOGY:

• To characterize the molecular profiles of four orphan ichthyosis subtypes, researchers collected tape strip RNA sequencing data from 27 patients with ichthyosis and 18 demographically matched healthy control individuals at Mount Sinai (New York City) and Northwestern University (Chicago) medical centers.
• Overall, nine patients had Netherton syndrome, six had congenital ichthyosiform erythroderma, seven had lamellar ichthyosis, and five had epidermolytic ichthyosis (the four subtypes: mean age, 17-26 years; 67%-80% women; 71%-89% White, 0%-20% Black, 0%-14% Asian individuals, and 0%-17% from other races; control individuals: mean age, 24.7 years; 78% women; 39% White; 22% Black, and 22% Asian individuals).
• RNA was extracted from 20 consecutive tape-strip samples per individual and analyzed using RNA-seq with Ion AmpliSeq Transcriptome Human Gene Expression Kits screening for more than 20,000 genes.
• Differential gene expression was defined as fold change > 2 and false discovery rate < 0.05. Spearman correlation analyses assessed relationships between normalized gene expression and Ichthyosis Area and Severity Index (IASI) scores, as well as between tape-strip and previously published biopsy transcriptomes.

TAKEAWAY:

• All ichthyosis subtypes demonstrated significant upregulation of Th17-associated markers (such as CCL20, IL36G, IL6) and Th22-associated markers (such as S100A7/8/9, PI3, SERPINB4) with fold changes ranging from 11 to 228 (P < .05). Netherton syndrome showed unique upregulation of IL17A/F, IL23A, and IL22.
• Netherton syndrome exhibited particularly strong Th2 dysregulation including IL13, CCL22/24, CCR4, and TNFSF4/OX40L, while IL4R and IL10 were also significantly increased in lamellar and epidermolytic ichthyosis (fold change, 9-25; P < .05).
• Disease severity measured by IASI scores correlated positively with ceramide synthase 3 (CERS3; correlation coefficient [R], 0.43, P = .013), several Th17 markers, and late cornified envelope genes, such as LCE1B/1C/1D/1F/2A/2C/2D (R, 0.49-0.61; P < .05).
• Correlations between tape-strip and biopsy transcriptomes for immune genes were strongest in Netherton syndrome (R, 0.47, P < .001) and congenital ichthyosiform erythroderma (R, 0.72; P < .001), while correlations for epidermal differentiation complex markers were significant across all subtypes (R, 0.38-0.61; P < .001).

IN PRACTICE:

This study highlighted “the feasibility of tape strips in measuring the immune and barrier abnormalities” in Netherton syndrome, congenital ichthyosiform erythroderma, lamellar ichthyosis, and epidermolytic ichthyosis, with “significant dysregulation that correlated with disease severity metrics and were overall concordant with changes measured in biopsy studies,” the authors wrote. Considering the “minimally invasive nature of this sampling modality,” tape strips, they added “may be a valuable means of studying these ichthyoses, given the pediatric predominance of these cohorts, the heterogeneity in treatment responses in each subtype, and the potential to evaluate changes longitudinally with treatment in future clinical trials.”

SOURCE:

The study was led by Madeline Kim, MD, MS, Icahn School of Medicine at Mount Sinai, New York City, and was published online on April 9 in the Journal of Investigative Dermatology.

LIMITATIONS:

The study limitations included small sample sizes and ichthyosis cohorts that had predominantly females and Whites, which limited generalizability.

DISCLOSURES:

This work was supported by awards from the National Center for Advancing Translational Sciences, National Institutes of Health (NIH), and the NIH/National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors declared serving as investigators or consultants for and having other ties with various sources including AbbVie, Regeneron, Janssen, Amgen, Allergan, Biomendics, Dermavant, Eli Lilly, and others. The other authors declared having no conflicts of interest. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.