Abstract
Periodontal Ehlers-Danlos syndrome (pEDS) is a rare hereditary disorder characterized by severe early-onset periodontitis with premature tooth loss, pretibial hyperpigmentation, and skin fragility. It is caused by mutant variants in the C1R and C1S genes that result in C4 cleavage and local complement cascade activation, as well as other possible consequences. However, the exact functional consequences of this activation remain unclear. To shed light on molecular mechanisms underlying pEDS and to identify novel molecular targets that may expand treatment strategies, we performed transcriptome profiling by RNA sequencing of monocytes and gingival fibroblasts from two patients with pEDS. Compared to normal controls, differential expression of genes was found only in monocytes but not gingival fibroblasts. Most of the significant genes were enriched in biological processes such as neutrophil-mediated immunity, response to bacterium, TNF-α and IL-17 pathway which are related to inflammation response and immune response. In disease ontology enrichment analysis, genes related to periodontal host defense, inflammatory response, skin disease, and vascular development, including MMP9, VEGFA, IL10, IL1A, IL1B, IL2RA, and IL6, were significantly enriched and also validated by qPCR and ELISA. Overall, the present study provides the transcriptomic data of pEDS for the first time and the distinct molecular features in monocytes of pEDS might serve as a tool to better understand the disease.