Autoantibodies as markers and possible mediators of scleroderma pathogenesis

Scleroderma or systemic sclerosis (SSc) is a systemic autoimmune disease characterized by a distinct, proliferative vasculopathy associated with skin thickening and fibrosis within internal organs and is associated with a unique autoimmune response. Within scleroderma, specific immune responses are strikingly associated with distinct clinical features. These autoantibody-defined clinical subgroups have distinct phenotypic and biological behavior, suggesting that the selection of specific immune targets has pathogenic consequences. This chapter focuses on the specificity and dynamics of these immune responses and the insights that they provide into disease mechanism, including as markers of key pathogenic events that initiate specific immune responses (e.g., mutation of scleroderma autoantigens in cancers), as well as potential roles as active mediators of damage of specific tissues. An understanding of the mechanisms underlying this extraordinary specificity may provide novel therapeutic targets or disease monitoring and management strategies.