Proinflammatory and profibrotic transcript profiles are overexpressed in central centrifugal cicatricial alopecia

Summary: Abstract Body: Central centrifugal cicatricial alopecia (CCCA) is the most common primary lymphocytic cicatricial alopecia typically affecting women of African descent. While gene expression profiling of CCCA-affected tissue has identified upregulation of profibrotic transcripts, the inflammatory/immune cell landscape of CCCA remains unclear. Further, current clinical practice employs non-specific, broad anti-inflammatory drugs including corticosteroids and oral antibiotics, with minimal targeted therapeutic options. To identify potential therapeutic targets, we used spatial transcriptomics to determine gene expression differences between affected and unaffected follicles in patients with clinically and biopsy confirmed CCCA. Spatial transcriptomics, using the NanoString GeoMx platform, was performed on six biopsies from African American female CCCA patients. A total of 88 follicles, were analyzed of which 61 were affected by CCCA and 27 were unaffected. Gene expression, gene ontology, and gene set enrichment analysis of affected vs unaffected follicles revealed significant upregulation of over 400 genes with multiple genes related to extracellular matrix reorganization (including MMP2, MMP14, VIM, and PDGFRA, adjusted p<0.01) and inflammation (including IL32, C1S, and TNFAIP2, adjusted p<0.01), and significant downregulation of lipid and fatty acid metabolism (including PLIN4 and APOC1, adjusted p<0.01). Additionally, PTGDS, the gene encoding prostaglandin D2 synthase was significantly upregulated (adjusted p<0.01). The upregulation of PTGDS suggests involvement of prostaglandin signaling in CCCA, possibly identifying a novel point of therapeutic intervention. These findings highlight a critical shift in the molecular landscape of CCCA-affected follicles, where upregulation of targetable profibrotic and inflammatory genes suggests a pathogenic mechanism which could inform future treatments. Noelle Desir¹, Iain Noel Encarnacion¹, Jordan C. Harris¹, Matthew L. Hedberg¹, Susan C. Taylor¹, John T. Seykora¹ 1. Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States. Minoritized Populations and Health Disparities Research