| Major histocompatility complex haplotypic associations in Felty's syndrome and large granular lymphocyte syndrome are secondary to allelic association with HLA-DRB1 *0401. | |
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MedLine Citation:
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PMID: 10817772 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To investigate the role of HLA class I in susceptibility to Felty's syndrome (FS) and large granular lymphocyte (LGL) syndrome. METHODS: Fifty caucasoid FS patients, and 55 patients with LGL syndrome, of whom 26 had arthritis and 29 did not, were studied. Complete HLA class I and HLA-DR typing including, where relevant, DRB1*04 subtyping was carried out by molecular methods. Comparison was made with 78 unselected healthy caucasoid controls and a further 29 DRB1*0401+ individuals. RESULTS: A significant association was found between HLA-A*02 and FS [odds ratio (OR) 3.9, 95% confidence interval (95% CI) 1.8-8.4, P = 0.0004]. At the B locus, there was an association between B*44 and LGL with arthritis [OR 3.5 (1.3-9.2), P = 0.01]. For HLA-Cw*0501, there was an association with FS [OR 4 (1. 7-9.2) P = 0.0008]. For both FS and LGL with arthritis, the extended haplotype HLA-A*02;B*44;Cw*0501;DRB1*0401 was significantly associated [OR 9.5 (2.6-35), P = 0.0001; OR 4.6 (1-22.4), P = 0.05, respectively]. There was no association between HLA class I or II and LGL without arthritis. All the allelic and haplotypic associations were lost on comparison with HLA-DRB1*0401+ controls. The strongest HLA association was with HLA-DRB1*0401 for FS [OR 27.9 (10.3-75.5), P = 10(-13)], and LGL with arthritis [OR 35.4 (9.6-131. 3), P = 10(-10)]. CONCLUSIONS: The major histocompatibility locus (MHC) associations with FS reported here are due to linkage disequilibrium with HLA-DRB1*0401. LGL syndrome with arthritis shows identical class II associations with FS, although there may be subtle immunogenetic differences between the two in the class I region. One of the extended haplotypes reported in a number of studies for FS and rheumatoid arthritis (summarized as HLA-A*02;Cw*0501; B*44;TNFb5;TNFa6;TNFd4;C4A*3;C4BQ*0;DRB1*0 401;DQB1*0301) is likely to be attributable to strong primary association with HLA-DRB1*0401, rather than to epistatic interaction between these loci. |
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Authors:
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G Coakley; D Brooks; M Iqbal; E Kondeatis; R Vaughan; T P Loughran; G S Panayi; J S Lanchbury |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Rheumatology (Oxford, England) Volume: 39 ISSN: 1462-0324 ISO Abbreviation: Rheumatology (Oxford) Publication Date: 2000 Apr |
Date Detail:
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Created Date: 2000-06-28 Completed Date: 2000-06-28 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100883501 Medline TA: Rheumatology (Oxford) Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 393-8 Citation Subset: AIM; IM |
Affiliation:
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Department of Rheumatology, 5th Floor, Thomas Guy House, Guy's, King's and St Thomas' School of Medicine, Guy's Hospital, London SE1 9RT, UK. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Alleles Arthritis, Rheumatoid / complications*, genetics Felty's Syndrome / genetics*, immunology* Female Genetic Predisposition to Disease HLA-DR Antigens / genetics* Haplotypes Humans Leukemia, Lymphoid / genetics Linkage Disequilibrium Major Histocompatibility Complex / genetics*, immunology Male Middle Aged Syndrome |
| Chemical | |
Reg. No./Substance:
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0/HLA-DR Antigens; 128338-86-3/HLA-DRB1 antigen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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