Autoantigenic epitopes on dna topoisomerase i

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Abstract
Objective. To elucidate the clinical and immunogenetic associations with reactivity to autoantigenic epitopes on DNA topoisomerase I (topo I) recognized by sera from patients with systemic sclerosis (SSc). Methods. Autoantigenic epitopes on topo I were identified by screening an epitope library constructed from topo I complementary DNA restriction fragments using autoimmune anti–topo I–positive sera as a probe. Epitope reactivities of sera from 43 anti–topo I–positive SSc patients were surveyed by immunoblotting, and associations with clinical symptoms and HLA–DR types were examined. Results. Four different epitope regions were identified on the topo I molecule. Immunoreactivity to the region encompassing amino acid residues 658–700, termed ER4, was found to be associated with diffuse cutaneous SSc, progressive pulmonary interstitial fibrosis, and poor prognosis for 15-year survival. SSc patients with ER4 reactivity frequently displayed the DR2/DRw52 phenotype. Conclusion. Molecular analysis of precise antigenic epitopes on topo I is helpful in classifying clinical subsets of SSc.