| Comparing HLA shared epitopes in French Caucasian patients with scleroderma. | |
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MedLine Citation:
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PMID: 22615829 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although many studies have analyzed HLA allele frequencies in several ethnic groups in patients with scleroderma (SSc), none has been done in French Caucasian patients and none has evaluated which one of the common amino acid sequences, (67)FLEDR(71), shared by HLA-DRB susceptibility alleles, or (71)TRAELDT(77), shared by HLA-DQB1 susceptibility alleles in SSc, was the most important to develop the disease. HLA-DRB and DQB typing was performed for a total of 468 healthy controls and 282 patients with SSc allowing FLEDR and TRAELDT analyses. Results were stratified according to patient's clinical subtypes and autoantibody status. Moreover, standardized HLA-DRß1 and DRß5 reverse transcriptase Taqman PCR assays were developed to quantify ß1 and ß5 mRNA in 20 subjects with HLA-DRB1*15 and/or DRB1*11 haplotypes. FLEDR motif is highly associated with diffuse SSc (χ(2) = 28.4, p<10-6) and with anti-topoisomerase antibody (ATA) production (χ(2) = 43.9, p<10-9) whereas TRAELDT association is weaker in both subgroups (χ(2) = 7.2, p = 0.027 and χ(2) = 14.6, p = 0.0007 respectively). Moreover, FLEDR motif- association among patients with diffuse SSc remains significant only in ATA subgroup. The risk to develop ATA positive SSc is higher with double dose FLEDR than single dose with respectively, adjusted standardised residuals of 5.1 and 2.6. The increase in FLEDR motif is mostly due to the higher frequency of HLA-DRB1*11 and DRB1*15 haplotypes. Furthermore, FLEDR is always carried by the most abundantly expressed ß chain: ß1 in HLA DRB1*11 haplotypes and ß5 in HLA-DRB1*15 haplotypes.In French Caucasian patients with SSc, FLEDR is the main presenting motif influencing ATA production in dcSSc. These results open a new field of potential therapeutic applications to interact with the FLEDR peptide binding groove and prevent ATA production, a hallmark of severity in SSc. |
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Authors:
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Doua F Azzouz; Justyna M Rak; Isabelle Fajardy; Yannick Allanore; Kiet Phong Tiev; Dominique Farge-Bancel; Marielle Martin; Sami B Kanaan; Philippe P Pagni; Eric Hachulla; Jean Robert Harlé; Rémi Didelot; Brigitte Granel; Jean Cabane; Jean Roudier; Nathalie C Lambert |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2012-05-15 |
Journal Detail:
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Title: PloS one Volume: 7 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2012 |
Date Detail:
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Created Date: 2012-05-22 Completed Date: 2013-01-08 Revised Date: 2013-02-26 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e36870 Citation Subset: IM |
Affiliation:
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Laboratoire d'Immunogénétique de la Polyarthrite Rhumatoïde, INSERM UMRs1097, Marseille, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Alleles Epitopes / genetics*, immunology European Continental Ancestry Group / genetics* Female Gene Frequency Genetic Predisposition to Disease HLA Antigens / genetics*, immunology* HLA-DQ beta-Chains / genetics, immunology HLA-DRB1 Chains / genetics, immunology HLA-DRB5 Chains / genetics, immunology Haplotypes Humans Linkage Disequilibrium Male Middle Aged RNA, Messenger / genetics Scleroderma, Systemic / genetics*, immunology* |
| Chemical | |
Reg. No./Substance:
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0/Epitopes; 0/HLA Antigens; 0/HLA-DQ beta-Chains; 0/HLA-DQB1 antigen; 0/HLA-DRB1 Chains; 0/HLA-DRB5 Chains; 0/RNA, Messenger |
| Comments/Corrections | |
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