303 Single-cell RNA sequencing of erythrodermic CTCL compared to atopic dermatitis and unspecific chronic erythroderma defines disease-specific markers

Sézary Syndrome (SS) and erythrodermic mycosis fungoides (MF) are advanced-stage disease variants of primary cutaneous T-cell lymphomas (CTCL). Erythroderma clonal blood involvement established markers an unfavorable outcome in CTCL, but these can also appear benign chronic inflammatory dermatoses. Of note, mechanisms guiding CTCL pathogenesis still only insufficiently understood, the differentiation from cases non-malignant erythroderma be a diagnostic challenge. By using single-cell RNA sequencing skin patients with erythroderma, we detected consistent presence CD4+ malignant clones CCR7+ SELL+ central memory phenotype SS MF patients. In individuals suffering unspecific by contrast, found pattern low-level expansion CD8A+ clones, that were identical both samples. Importantly, lacked type 2 immune skewing typically atopic dermatitis, i.e., strong increases IL13-associated pathways. patients, cytotoxic mediators such as GNLY upregulated skin, strongly increased expression pro-inflammatory cytokine IL22 especially lesions. Overall, disease-specific pathogenic signatures different those dermatitis individuals. These data might help to improve diagnostics contribute development better targeted treatment strategies for