Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI116703

The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma).

M Kuwana, J Kaburaki, Y Okano, H Inoko, and K Tsuji

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Find articles by Kuwana, M. in: PubMed | Google Scholar

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Find articles by Kaburaki, J. in: PubMed | Google Scholar

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Find articles by Okano, Y. in: PubMed | Google Scholar

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Find articles by Inoko, H. in: PubMed | Google Scholar

Department of Medicine, Keio University School of Medicine, Tokyo, Japan.

Find articles by Tsuji, K. in: PubMed | Google Scholar

Published September 1, 1993 - More info

Published in Volume 92, Issue 3 on September 1, 1993
J Clin Invest. 1993;92(3):1296–1301. https://doi.org/10.1172/JCI116703.
© 1993 The American Society for Clinical Investigation
Published September 1, 1993 - Version history
View PDF
Abstract

HLA class II alleles were determined using the PCR-RFLP method in Japanese systemic sclerosis (scleroderma) patients with (n = 28) or without (n = 34) anti-topoisomerase I antibodies (anti-topo I). Either the DQB1*0601 or *0301 allele was recognized in all anti-topo I positive patients, compared with 44% of anti-topo I negative patients (P < 0.00001, relative risk [RR] > 41) or 58% of Japanese healthy control subjects (P < 0.00001, RR > 24). Tyrosine at position 26 in the second hypervariable region in the beta 1 domain of the DQB1 gene is common to these two alleles and is not present in any other known DQB1 alleles. We also examined immunoreactivities of anti-topo I positive sera to four different autoantigenic B cell epitopes of topo I molecule that were expressed as recombinant fusion proteins. One major B cell epitope, located within the region corresponding to amino acid residues 74-248, was perfectly associated with the amino acid sequence FLEDR at positions 67-71 in the beta 1 domain of the DRB gene. Two other epitopes, corresponding to 316-441 or 658-700, were associated with the serologically defined HLA-DR52 antigen. Patients with both FLEDR and DR52 demonstrated higher anti-topo I antibody titers. These results suggest that the HLA-DR and DQ genes together control the autoimmune response to topo I in systemic sclerosis.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 1296
page 1296
icon of scanned page 1297
page 1297
icon of scanned page 1298
page 1298
icon of scanned page 1299
page 1299
icon of scanned page 1300
page 1300
icon of scanned page 1301
page 1301
Version history
  • Version 1 (September 1, 1993): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts