Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis

B. Grigolo, I. Mazzetti, R. M. Borzì, I. D. Hickson, M. Fabbri, L. Fasano, R. Meliconi, A. Facchini

Research output: Contribution to journalArticle

Abstract

Autoantibodies against DNA topoisomerase II α have been identified in the sera of patients with idiopathic pulmonary fibrosis (IPF). To map topoisomerase II autoepitopes, we tested by ELISA and immunoblotting the IPF anti-topoisomerase II-positive sera against a series of recombinant proteins which covered the full length of topoisomerase II α. Specific patterns of reactivity were observed, indicating the existence of multiple epitopes on topoisomerase II, either highly complex or conformational/discontiguous or conformational/contiguous ones. The latter resided in amino acid residues 854-1147 and 1370-1447. A detailed analysis of these regions was undertaken, but we were not able to pinpoint a sequential peptide-sized epitope, or any significant homology with foreign pathogens. Further, we observed a significant correlation between the progression from a contiguous to a quaternary/tertiary structure-dependent autoepitope and the disease duration but not with the disease severity. Therefore, this result supports the hypothesis that anti-topoisomerase II autoreactivity evolves following an antigen-driven process.

Original languageEnglish
Pages (from-to)339-346
Number of pages8
JournalClinical and Experimental Immunology
Volume114
Issue number3
DOIs
Publication statusPublished - 1998

Keywords

  • Autoantibodies
  • Epitope mapping
  • Idiopathic pulmonary fibrosis
  • Topoisomerase II

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Mapping of topoisomerase II α epitopes recognized by autoantibodies in idiopathic pulmonary fibrosis'. Together they form a unique fingerprint.

  • Cite this