The vascular perspective of systemic sclerosis: Of chickens, mice and men

Systemic sclerosis (SSc), or scleroderma, is an autoimmune connective tissu e disease characterized by structural and functional vascular abnormalities , perivascular mononuclear cell infiltration, and increased deposition of e xtracellular matrix in skin and internal organs. The initial stages of SSc are generally not accessible for analysis in man, therefore, the availabili ty of appropriate animal models is of great importance for the elucidation of the pathogenesis of this disease. UCD-200 chickens show the entire clini cal, histopathological and serological spectrum of SSc, whereas tight skin (Tsk)1/+ and Tsk2/+ mice, other animal models of scleroderma, lack the vasc ular injury. A parallel comparative study of skin biopsies of UCD-200 chick ens and human SSc patients revealed that endothelial cell apoptosis, induce d by anti-endothelial cell antibody (AECA)-dependent cellular cytotoxicity, is a primary event in the pathogenesis of SSc. This review focuses on rece ntly established data on endothelial cell injury in animals with spontaneou s disease and humans, AECA, adhesion molecules and cytokine profiles that s upport a vascular pathogenesis in scleroderma. Copyright (C) 1999 S. Karger AG. Basel.