Biomarkers in systemic sclerosis

Abstract

Systemic sclerosis is an autoimmune inflammatory disorder of unknown etiologycharacterized b y pronounced fibroproliferative alterations in the microvasculature, and frequent cellular and humoral immunity abnormalities, culminating in a severe and often progressive fibrotic process. Numerous biomarkers reflecting the three main pathogenetic mechanisms in systemic sclerosis have been described; however, aside from several disease-specific autoantibodies, other biomarkers have not been thoroughly validated and require further study. Thus, there is an unmet need for validated biomarkers for diagnosis, disease classification, and evaluation of organ involvement and therapeutic response in systemic sclerosis.

Figure 1. General overview of the pathogenesis of systemic sclerosis

Illustrations on the bottom row show examples of (A) the fibrotic process (biopsy of skin), (B) microvascular alterations in pulmonary arterioles, (C) autoantibodies detected by immunofluorescence and (D) mononuclear inflammatory cell infiltrates in affected skin. Adapted with permission from [3].

Figure 2. Postulated sequence of events in the pathogenesis of systemic sclerosis

Sequence of pathogenic processes leading to tissue fibrosis and autoantibody production. The process is initiated by microvascular endothelial injury, which induces chronic inflammation with participation of macrophages and T lymphocytes, as well as B-lymphocyte activation, leading to autoantibody production. The secreted products from the inflammatory cells result in fibroblast activation and phenotypic conversion into myofibroblasts; key events in the development of fibrosis. ANA: Antinuclear antibody; ECM: Extracellular matrix; Scl-70: Scleroderma-70 antibody (anti-DNA topoisomerase 1).