Inflammation and Immunity in Systemic Sclerosis

Systemic sclerosis (SSc) pathogenetic events originate from altered homeostasis favored by genetic predisposition, environmental cues, and a variety of endogenous and exogenous triggers. Within this framework, the breaking of immune tolerance leading to adaptive immune responses play fundamental roles. SSc shares with other systemic autoimmune disorders (SADs) genetic components and biological abnormalities. These include gene variants involving effectors of the adaptive immune system as well as the production of autoantibodies. It should be noted that no established animal model is able to fully reproduce the heterogeneous clinical phenotypes of SSc upon immunization or passive transfer of immune cells or antibodies. This fact underlies our incomplete knowledge of the contribution of autoimmunity in the development of SSc. This notwithstanding, the enormous body of work that has been generated over the last several decades to investigate SSc pathobiology indicates that the adaptive immune system presents abnormalities significantly associated with distinct SSc phenotypes and thus possibly linked to disease development and progression. T cells may recognize autoantigens, some of which may result from cross-reactivity with neo-epitopes generated during cancer development. Conventional and SSc-specific T-cell subsets modulate both fibroblasts as well as endothelial cell dysfunction. Besides autoantibodies directed against ubiquitous antigens important for enhanced clinical classification, antigen-specific agonistic autoantibodies may have a pathogenic role. This chapter will provide an integrated view of the immune-inflammatory abnormalities observed in SSc and will focus on soluble mediators and cells belonging to the adaptive immune system. A general introduction is provided in the previous chapter dedicated to innate immunity.