Patients treated with procainamide for cardiac arrhythmias commonly develop anti-histone antibodies and often frank symptoms of systemic lupus erythematosus. The mechanism by which this etiologic agent elicits autoantibodies and lupus symptoms is unknown and is the long term objective of this investigation. Insights will be sought by a systematic evaluation of the clinical and laboratory changes which take place in a group of patients prospectively studied during development of signs and symptoms. Preliminary results suggest that highly restricted autoantibody responses occur in some patients.
We aim to examine this phenomenon by delineating the precise specificity of anti-histone antibodies and enumerating the antibody populations within a serum. This will be done by solid phase adsorption on individual histones and by examination of the histone binding specificities of antibodies affinity purified on a panel of individual histones. Mouse monoclonal antibodies having a variety of histone-binding specificities will be used to compete with human antibodies for binding to the same antigen. Determination of the number and kinds of drug-elicited autoantibodies will provide the framework for possible models for antibody genesis at the B-cell level. The role of anti-histone antibodies in the pathogenesis of drug-induced lupus will be studied in context of the complement system. The capacity of different types of anti-histone antibodies and different forms of histones to participate in complement activation will be investigated, and evidence for complement activation in vivo will be sought. Relationships among these parameters will be of predictive value in managing drug-treated patients and provide insights into the pathogenic mechanisms which underly this type of systemic autoimmune disease.
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