Molecular phenotyping of keloid skin samples suggests polar immune dysregulation
Jonathan Bar2, Camille Rothenberg-Lausell2, J. Roscoe Wasserburg*1, Digpal Gour2, Ying Liu2, Yeriel Estrada2, Amira Chowdhury2, Peter Taub3, Emma Guttman-Yassky2
1SUNY Downstate College of Medicine, Brooklyn, NY; 2Department of Dermatology, Icahn School of Medicine at Mount Sinai, New York, NY; 3Department of Plastic and Reconstructive Surgery, Icahn School of Medicine at Mount Sinai, New York, NY
Keloids are a common wound healing pathology that impact both function and aesthetic objectives. Keloid scaring is reported as high as 16 percent among African and Hispanic patients, and highly prevalent among Asian populations as well. However current genetic analysis has not elucidated a consistent pattern. Current therapeutic modalities lack efficacy in reversing the systemic phenotype of this disease. Standard of care for poorly controlled disease includes local corticosteroid injections and may include surgery, cryotherapy, chemotherapy and radiation. This study focuses on investigating the immune-basis hypothesis for keloid formation and propagation to provide insight into their formation and pathogenesis.
Twenty-seven patients with keloids and twenty-three patients without keloids were enrolled in this study, with African Americans being the predominant racial/ethnic group represented. Skin biopsies from keloid and control patients were analyzed with RNA-seq and Olink proteomics.
There was significant dysregulation in wound healing and epidermal barrier genes. In addition, significant upregulation occurred in key Th1, Th2, and several Th17 immune pathway genes. Many of these genes are potential biomarkers used as therapeutic targets including OX40L, OX40, IL4R, JAK3; FDR<0.05. Significant correlations between clinical characteristics and RNA-seq data, such as number of keloids per patient, correlates with IL-19 and IL-2 levels (r>0.5, p<0.05). This trend was similarly demonstrated with the Olink proteomic analysis which correlated highly with the RNA-seq data showing upregulation of OX40 and IL-4R (FDR<0.05).
These findings suggest a possible link between keloids and immune skewing, particularly in patients with a higher number of keloids. Furthermore, these findings indicate that patients with keloids may benefit from a systemic immune-based treatment.
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