Direct binding of anti-DNA topoisomerase I autoantibodies to the cell surface of fibroblasts in patients with systemic sclerosis.

摘要: Objective Fibroblasts play a crucial role in the development of systemic sclerosis (SSc), and antifibroblast antibodies (AFAs) capable inducing proinflammatory phenotype fibroblasts have been detected sera SSc patients. This study examined prevalence AFAs other diseases possible correlation between known antinuclear antibody specificities patients. Methods Sera from 99 patients with SSc, 123 autoimmune nonautoimmune diseases, 30 age- sex-matched healthy controls were examined. AFA was assessed by flow cytometry further characterized indirect immunofluorescence, enzyme-linked immunosorbent assay (ELISA), immunoblotting. Anti–topoisomerase I (anti–topo I) purified affinity chromatography on topo I. Results AFAs more common (26.3%) than any disease groups studied. The presence significantly associated pulmonary involvement death. AFA-positive bound to all human rodent tested, but not primary endothelial cells or smooth muscle cells. All strongly reacted ELISA binding intensity correlated reactivity against immunoblots fibroblast extracts immunofluorescence pattern typical anti–topo permeabilized Total IgG affinity-purified found react surface unpermeabilized as well confocal microscopy. Conclusion This is first report establishing that are and, furthermore, themselves display activity reacting determinants at surface.