This research project focuses on the effects of Systemic Sclerosis (SSc) patient sera on the endothelial glycocalyx (eGC). Among the large variety of autoantibodies (Abs) present in the sera of patients suffering from SSc, functionally active Abs against angiotensin II type 1 receptor (ATR1) are found in approximately 85% of SSc patients, where the high concentrations of these Abs are associated with more aggressive disease and poor prognosis. A study showed that IgG isolated from SSc patients containing Abs targeting AT1R induces endothelial cell (EC) activation in vitro. AT1R, a member of the G protein-coupled receptor (GPCR) family, plays a central role in regulating vascular tone, extracellular matrix generation, fibrosis, and inflammation. This receptor is expressed on the surface of various immune cells such as endothelial cells and monocytes. The binding of these autoantibodies to AT1R on cells leads to inflammatory responses and increased expression of adhesion molecules and cytokines.

This project aims to 1) Evaluate the effect of patient sera on eGC condition of Human pulmonary microvascular endothelial cells (HPMECs) and Human umbilical vein endothelial cells (HUVECs) using Atomic force microscopy (AFM); 2) Validate In-vivo the effects of AT1R Abs on the eGC that were seen in-vitro using sublingual videomicroscopy coupled with GlycoCheck™ software; 3) Assess changes in the expression of cytokines using an Olink proteomics assay; and 4) Evaluate the effect of patient sera on monocyte adhesion to endothelial cells using AFM CellHesion technique.

These findings will advance the understanding of how AT1R antibodies contribute to SSc pathogenesis and could inform new therapeutic approaches targeting these pathways.