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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: JCI | PubMed | Google Scholar

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

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

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

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

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

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

Find articles by Tsuji, K. in: JCI | 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
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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.

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