Unveiling the inflammatory and cardiovascular signatures in keloid pathogenesis through multiomic analysis

Summary: Abstract Body: Keloids are disfiguring scars resulting from an abnormal wound-healing response, with a higher prevalence among Asian and Black populations. Despite their impact, no targeted treatments exist, likely due to a limited understanding of their pathogenesis. This study aimed to identify disease-specific molecular mechanisms through multiomic profiling of keloid serum and skin samples. Serum and lesional skin from 34 individuals with keloids and 18 healthy controls were analyzed using the Olink Proteomics assay (552 markers). Skin samples were further assessed by RNA sequencing and PCR and correlated with clinical severity metrics. Results revealed significantly (fold-change>1.3; p<0.05) elevated proinflammatory serum proteins, including TNF, Urokinase receptor, and LPL, immune-regulatory markers such as IL10, extracellular matrix development as MATN2, and TGF-β signaling related proteins such as BMP6. Skin biomarkers showed polar immune dysregulation with increased expression of innate (IL6), Th1 (CXCL10, CXCL11), Th2 (CCL17), and Th17 (CCL20) proteins. Additional findings included heightened Wnt activation (RSPO3 upregulated, WIF1 downregulated) and profibrotic markers (MMP2, SPARC, SERPINE1). RNASeq and PCR analysis corroborated proteomic results, and skin proteomics strongly correlated with RNA transcriptomics (ρ=0.58, p<0.01). Moreover, protein expression in skin and/or serum showed significant correlations with clinical severity metrics (e.g., keloid size was correlated with CCL20; ρ=0.4, p<0.05). This study highlights inflammatory and cardiovascular signatures in keloid skin and serum, revealing novel molecular mechanisms that could potentially inform therapeutic development. Jonathan Bar^{1, 5}, Ester Del Duca^{1, 2}, Curtis Tam¹, Dev Patel¹, Megan Lau^{1, 3}, Eden David¹, J Roscoe Wasserburg⁴, Peter Taub⁴, Emma Guttman-Yassky¹ 1. Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 2. Dermatology, Universita degli Studi di Roma La Sapienza, Rome, Lazio, Italy. 3. New York University, New York, NY, United States. 4. Plastic and Maxillofacial Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, United States. 5. Tel Aviv University, Tel Aviv, Tel Aviv, Israel. Translational Studies: Cell and Molecular Biology