AUTOANTIGENIC EPITOPES ON DNA TOPOISOMERASE-I - CLINICAL AND IMMUNOGENETIC ASSOCIATIONS IN SYSTEMIC-SCLEROSIS

作者:KUWANA M; KABURAKI J; MIMORI T; TOJO T; HOMMA M
来源:Arthritis and Rheumatism, 1993, 36(10): 1406-1413.
DOI:10.1002/art.1780361013

摘要

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.

  • 出版日期1993-10

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