Autoimmunity in Systemic Sclerosis: Overview

Abstract

Systemic sclerosis (SSc) is characterized by autoimmunity and tissue fibrosis of several organs. Although the pathogenic relationship between systemic autoimmunity and the clinical manifestations of SSc remains unknown, SSc patients display a variety of abnormal immune activation including the production of disease-specific autoantibodies. Previous studies have demonstrated that immune cells, mainly including T and B cells, play a critical role in systemic autoimmunity and disease expression, though the role of autoimmunity in generating the clinical and pathologic phenotype in SSc remains uncertain. Activation and polarization of T cells can contribute to a profibrotic environment. Oligoclonal T cells, preferentially producing type 2 cytokines, exist in affected tissues and peripheral blood early in the disease course and seem to be participating in the establishment of fibrosis. Similarly, SSc patients have B cell abnormalities characterized by chronic hyper-reactivity of memory B cells, possibly due to CD19 overexpression. CD19 is a crucial regulator of B cell activation. Recent studies demonstrated B cells from SSc patients show an upregulated CD19 signaling pathway that induces SSc-specific autoantibody production in SSc mouse models. Although distinct subsets of autoantibodies do not have a proven pathogenic role, they are selectively associated with unique disease manifestations. Collectively, autoimmunity in SSc is most likely participating in SSc-specific tissue damage. If revealed the mechanisms of autoimmunity in SSc, these knowledge could lead to new disease-modifying therapeutic strategies directed at SSc-specific immune effector pathways.