Anti—topoisomerase i antibodies in silica‐associated systemic sclerosis. A model for autoimmunity

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Abstract
Objective. To determine the frequency and type of autoantibodies present in patients with systemic sclerosis (SSc) associated with an established environmental toxin. Methods. Clinical data and sera were available from 14 men with silica‐associated SSc who had developed SSc after at least 2 years of exposure to silica at work. Controls included 27 men with silicosis without SSc. Autoantibodies were measured by immunodiffusion, immunoblotting, and functional inhibition of topoisomerase I (topo I). Results. Nine of the 14 patients with silica‐associated SSc had anti—topo I antibodies. All anti—topo I antibodies in the patients with silica‐associated SSc and in 14 anti—topo I—positive patients with idiopathic SSc were directed at an active site of topo I, or at least sterically inhibited its function. One patient with silica‐associated SSc had anticentromere antibodies. Unexpectedly, 2 patients with silicosis who had no symptoms of a connective tissue disease had autoantibodies to Ro/SS‐A and La/SS‐B autoantigens. Conclusion. Anti—topo I antibodies are the predominant autoantibodies present in silica‐associated SSc. The generation of anti—topo I antibodies in genetically susceptible individuals may depend partly on the patient's sex and on the site of organ involvement, and may be triggered by silica particles acting as an immune adjuvant.