Transcriptomic profiling of lesional and healthy skin in pemphigus patients reveals IL-17–driven immune response

Pemphigus is a rare autoimmune blistering skin disease characterized by autoantibodies against desmoglein 1 and/or 3. To better understand the immunopathology of pemphigus, we performed RNA sequencing of lesional skin biopsies from pemphigus patients (n=6) and compared them to skin biopsies from healthy controls (n=6). Our data reveal an IL-17/IL-21–dominated transcriptional signature, with upregulation of inflammatory cytokines, chemokines, and tissue remodeling genes. These findings support the hypothesis that pemphigus pathogenesis is driven by a TH17/TFH17-type immune response and offer insights into potential therapeutic targets. Skin punch biopsies were obtained from six patients with clinically active pemphigus (lesional skin) and six age- and sex-matched healthy individuals (control skin). Total RNA was isolated and quality-controlled using Nanodrop, Qubit, and Bioanalyzer. RNA-seq libraries were prepared and sequenced using the Illumina NextSeq 500 platform (single-end, 75 bp). Raw reads were aligned to the GRCh37 reference genome using STAR, and gene-level expression quantification was performed with Subread.