Immunological basis of systemic sclerosis

Systemic sclerosis (SSc) is a disease of unknown aetiology characterized by excessive and often progressive fibrosis in skin and multiple internal organs, an aberrant immune activation marked by multiple humoral and cellular immunological abnormalities and pronounced alterations in the microvasculature. The pathogenesis of SSc is complex and, although progress in the understanding of the multiple processes underlying SSc has been made in recent years, no single unifying hypothesis explaining all aspects of this disease exists. Recent studies have suggested that the activation of the immune system is a key stimulus to vascular abnormalities and fibrosis. Once T-cells are activated, they infiltrate the skin lesions early, and produce the profibrotic cytokine IL-4. They are also required for autoantibody production. B-cells may contribute to fibrosis, as deficiency of CD19, a B-cell signal transduction molecule, results in decreased fibrosis in animal models. In recent years, clinical advances have occurred in parallel with a better understanding of the underlying disease mechanisms. In this article, the immunological aspects and multiple altered immunological processes found in SSc are discussed.