Proteome profiling for hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders to unravel pathogenetic mechanisms and identify potential biomarkers supporting clinical diagnosis – concluso

Hypermobile Ehlers-Danlos syndrome/hypermobility spectrum disorders (hEDS/HSD) is the most common form of EDS, which is dominated by an extremely variable phenotype and a high rate of chronic disability. The etiology of hEDS/HSD is unknown, and patients are still without a definitive molecular diagnosis. Our previous studies demonstrated that hEDS/HSD fibroblasts exhibit a widespread extracellular matrix (ECM) disarray and significant expression changes of several genes involved in connective tissue architecture, and related to inflammatory, pain, and immune responses. These cells also show a proinflammatory matrix-degrading phenotype with a range of phenotypic features that are typical of myofibroblasts. Taking advantage from our cell model, in this project we plan to profile the proteome of hEDS/HSD patients’ dermal fibroblasts to identify specific proteomic signatures and perturbed biological processes that contribute to the pathophysiology of hEDS/HSD.