AUTOANTIBODIES - DIAGNOSTIC FINGERPRINTS AND ETIOLOGIC PERPLEXITIES

Autoantibodies are a hallmark of systemic rheumatic diseases, organ-sp ecific autoimmune diseases and paraneoplastic syndromes. Cell biologis ts have used autoantibodies as probes to define the structure and func tion of novel macromolecules and to determine the chromosomal location of their respective genes. The observation that many autoantibodies a ppear before the clinical expression of disease suggests that they are not epiphenomena. Some autoantibodies are disease-specific markers an d are an aid to establishing a diagnosis. Although it has been difficu lt to link autoantibodies to pathogenesis, they can be used to predict disease progression and outcome. For example, autoantibodies directed against topoisomerase I are associated with progression of scleroderm a to diffuse skin involvement and severe systemic disease, whereas ant ibodies to centromere proteins predict a more slowly progressive disea se and development of a limited variant of scleroderma. Certain models of autoantibody production hold promise of a clearer understanding of the mechanisms that underlie autoimmunity. Drugs such as procainamide and hydralazine induce the production of chromatin autoantibodies. Ex posure to heavy metals (e.g., mercury) is also linked to the developme nt of autoantibodies. The data provide evidence that the autoimmune re sponse is driven by autoantigens, which are multimolecular complexes i nvolved in essential cellular functions.