CD40LG and systemic sclerosis: Soluble CD40L (sCD40L), the circulating form measured in the proteomics assay, is the ligand of CD40, which also binds to other receptors on endothelial cells and promotes vascular pathology.53 Elevated soluble CD40L levels have been found in patients with SSc and are associated with its vascular manifestations.54 Overall, the complex B cell dysregulation mediating genetically determined reduced CD40 expression in SSc warrants further investigation.