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.

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Families with more than one case of scleroderma are unusual. Four families each with two members (in one case monozygotic twins) with scleroderma (systemic sclerosis, SSc) were identified. Clinical, immunogenetic and autoantibody studies were carried out. Multicase SSc families cited in the literature were reviewed. Each family pair shared cutaneous subset of disease severity, and SSc-associated autoantibody. HLA typing showed two pairs shared an HLA-DR allele associated with scleroderma (DR3 or DR5), while one also had alleles reported in association with their SSc-specific autoantibody. Review of dates and ages of onset suggested that the timing of onset of scleroderma is more likely to have an environmental trigger than to be encoded genetically.

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