Document Detail

Comparing HLA shared epitopes in French Caucasian patients with scleroderma.
MedLine Citation:
PMID:  22615829     Owner:  NLM     Status:  MEDLINE    
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.
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
Related Documents :
9678309 - Brain tumors in the elderly: recent trends in a minnesota cohort study.
21036949 - White matter abnormalities in methcathinone abusers with an extrapyramidal syndrome.
20421059 - Scheduled repeat ct scanning for traumatic brain injury remains important in assessing ...
7355669 - Central nervous system involvement in adult-onset gaucher's disease.
8856789 - Severe stealth virus encephalopathy following chronic-fatigue-syndrome-like illness: cl...
11255629 - Brain hypothermia relieves severe brain swelling following acute major cerebral artery ...
1121229 - The pickwickian syndrome with hypertrophy of tonsils: a re-appraisal.
18076429 - Symptoms experienced by patients with peripheral vestibular disorders: evaluation of th...
11332199 - Severe fenitrothion poisoning complicated by rhabdomyolysis in psychiatric patient.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-05-15
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-05-22     Completed Date:  2013-01-08     Revised Date:  2013-06-24    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e36870     Citation Subset:  IM    
Laboratoire d'Immunogénétique de la Polyarthrite Rhumatoïde, INSERM UMRs1097, Marseille, France.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Epitopes / genetics*,  immunology
European Continental Ancestry Group / genetics*
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
Linkage Disequilibrium
Middle Aged
RNA, Messenger / genetics
Scleroderma, Systemic / genetics*,  immunology*
Reg. No./Substance:
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

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Combined use of serum adiponectin and tumor necrosis factor-alpha receptor 2 levels was comparable t...
Next Document:  Enzymatic analysis of recombinant Japanese encephalitis virus NS2B(H)-NS3pro protease with fluorogen...