1583 Degos disease is characterized by cytotoxic transcriptome centering on CD8 T cells

Degos disease is an extremely rare disease, manifesting in the skin as necrotic papules. It may be skin-limited but prognosis poor for systemic involvement. primarily considered a microthrombopathy, pathophysiology remains elusive and lacks effective treatments. We found prominent lymphocytic infiltration targeting epidermis vasculature lesional of patients, suggesting immune-mediated pathophysiology. Single-cell RNA sequencing (scRNA-seq) analysis from both acute scarring lesions patients revealed inflammatory milieu with increased proportion lymphoid cluster that was enriched type I II IFN signaling pathways. A subset CD8 T cells highly expressed IFNG cytotoxic genes including GZMB, consistent responses observed epidermis. Immunohistochemistry confirmed Granzyme B phosphorylated STAT1 expression, indicating JAK-STAT pathway activation. scRNA-seq peripheral blood exuberant IFN-g signatures along elevated were greater vs. limited reflecting magnitude inflammation former, their involvement multiple organs. cerebrospinal fluid patient gene profiles well monocytes. These results suggest involving across The upregulation IFN-responsive highlight cytokine receptor pathways, such JAK- STAT pathway, attractive therapeutic targets disease.