Systemic sclerosis (SSc) is characterized by tissue fibrosis, obliterative microangiopathy, and immune abnormalities. The role of autoimmunity in generating the clinical and pathologic phenotype in SSc remains uncertain. Distinct subsets of antinuclear antibodies are selectively associated with unique disease manifestations but do not have a proven pathogenic role. A new class of autoantibodies recognizing cellular or extracellular matrix antigens has been recognized in SSc patients. They seem to directly activate pathways that may contribute to SSc-specific tissue and vascular damage. Data confirms that activation and polarization of T cells can contribute to a profibrotic environment. Also, activated immune effector cells can promote vascular obliterative damage through direct cytotoxic pathways targeting the endothelium or by inducing proinflammatory molecules. Technologies are emerging to accurately measure the autoantigen-specific T-cell response in SSc patients. Perturbed B-cell homeostasis has been reported in SSc. If confirmed in-vivo, these advances could lead to new disease-modifying therapeutic strategies directed at SSc-specific immune effector pathways.
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