Autoantibodies in 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. While vascular damage is almost universal in scleroderma, disease expression is heterogeneous in terms of phenotypic characteristics and disease course. Nevertheless, clear clinical subtypes can be discerned. The limited cutaneous form of scleroderma (lcSSc) is characterized by skin thickening on the distal limbs, face and neck, and an increased prevalence of isolated pulmonary hypertension and ischemic digital loss. In contrast, the diffuse form of the disease also involves more proximal skin, and affects visceral organs, including the lung, heart, gastrointestinal tract, skeletal muscle and kidneys, with attendant negative effects on mortality. There are striking associations between specific autoantibodies and the distinct phenotypic subsets of scleroderma. These associations are clinically useful, suggesting, at a minimum, that the different autoantibodies are reporting on specific circumstances which underlie disease propagation in different tissues. It is also possible that specific autoantibodies play a direct pathogenic role in the propagation and amplification of autoimmune reactions and pathology in SSc. This chapter reviews some of the interesting insights which autoantibodies and their specificity provide into scleroderma pathogenesis.