| Severe systemic sclerosis with anti-topoisomerase I antibodies is associated with an HLA-DRw11 allele. | |
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MedLine Citation:
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PMID: 7928439 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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SSc is an autoimmune connective tissue disease in which strong HLA associations have not been described. Anti-topo I antibodies are recognized, in general, in SSc patients with diffuse cutaneous involvement, whereas anti-ACAs are found in individuals with limited cutaneous involvement. We studied 95 Caucasian SSc patients, 44 with anti-topo I antibodies and 51 with neither anti-topo I nor ACA, for HLA-DR associations by using DNA typing techniques. We analyzed 181 normal Caucasian individuals in the same fashion. A significant association was observed in the anti-topo-I-positive patients with DRw11 (p = 1.7 x 10(-6), RR 4.2). The distribution of DRw11 alleles in these patients was significantly different from that observed in controls and could be accounted for by an increase in the frequency of the DRB1*1104 allele (p = 1.2 x 10(-9), RR 9.5). The DRw11 alleles were also associated with SSc with more tendon friction rubs (p = 0.006), which is a marker of more severe disease. In addition, a strong association was observed with anti-topo I antibodies and a particular sequence (aa 71-77) of the DQB1 chain (p = 0.02, RR 2.2). HLA associations in the case of SSc patients with anti-topo I antibodies are complex and involve at least two genes: HLA-DRw11, which appears to play a major role in determining the severity of the disease, and a DQ sequence, which associates with the development of the anti-topo I antibodies. |
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Authors:
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P A Morel; H J Chang; J W Wilson; C Conte; S L Saidman; J D Bray; D J Tweardy; T A Medsger |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Human immunology Volume: 40 ISSN: 0198-8859 ISO Abbreviation: Hum. Immunol. Publication Date: 1994 Jun |
Date Detail:
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Created Date: 1994-11-14 Completed Date: 1994-11-14 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 8010936 Medline TA: Hum Immunol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 101-10 Citation Subset: IM |
Affiliation:
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Division of Rheumatology and Clinical Immunology, University of Pittsburgh School of Medicine, PA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alleles Autoantibodies / immunology* DNA Topoisomerases, Type I / immunology* Female Gene Frequency HLA-DQ Antigens / genetics* HLA-DR Antigens / genetics* Humans Male Middle Aged Scleroderma, Systemic / genetics*, immunology* |
| Grant Support | |
ID/Acronym/Agency:
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2P30 CA47904/CA/NCI NIH HHS; AM21393/AM/NIADDK NIH HHS; N01 AI 15115/AI/NIAID NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Autoantibodies; 0/HLA-DQ Antigens; 0/HLA-DR Antigens; EC 5.99.1.2/DNA Topoisomerases, Type I |
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