Autoantibodies directed against a variety of nuclear, cytoplasmic and extracellular autoantigens are a serological hallmark of systemic sclerosis. This review provides an overview of the history and clinical association of many of the autoantibodies identified in SSc sera to date. Some of these autoantibodies predate the clinical diagnosis of SSc, some are pathogenic while others have no apparent role in pathogenesis. It was once thought that the autoantibody spectrum of individual SSc sera were less complex than other systemic autoimmune rheumatic diseases with respect to heterogeneous B cell responses reflected in circulating autoantibodies. However, with the advent of array technologies, there is now an unprecedented capability to detect multiple autoantibodies in an individual serum and this long held tenet of clinical diagnostic immunology is being reexamined.
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