Comparing HLA shared epitopes in French Caucasian patients with scleroderma.
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...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3352938?pdf=render |
| _version_ | 1811275943203831808 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Doua F Azzouz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T23:47:43Z |
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| id | doaj.art-0b64ed02720b4926a6d19776e6caa38a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T23:47:43Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-0b64ed02720b4926a6d19776e6caa38a2022-12-22T03:11:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0175e3687010.1371/journal.pone.0036870Comparing HLA shared epitopes in French Caucasian patients with scleroderma.Doua F AzzouzJustyna M RakIsabelle FajardyYannick AllanoreKiet Phong TievDominique Farge-BancelMarielle MartinSami B KanaanPhilippe P PagniEric HachullaJean Robert HarléRémi DidelotBrigitte GranelJean CabaneJean RoudierNathalie C LambertAlthough 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.http://europepmc.org/articles/PMC3352938?pdf=render |
| spellingShingle | 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 Comparing HLA shared epitopes in French Caucasian patients with scleroderma. PLoS ONE |
| title | Comparing HLA shared epitopes in French Caucasian patients with scleroderma. |
| title_full | Comparing HLA shared epitopes in French Caucasian patients with scleroderma. |
| title_fullStr | Comparing HLA shared epitopes in French Caucasian patients with scleroderma. |
| title_full_unstemmed | Comparing HLA shared epitopes in French Caucasian patients with scleroderma. |
| title_short | Comparing HLA shared epitopes in French Caucasian patients with scleroderma. |
| title_sort | comparing hla shared epitopes in french caucasian patients with scleroderma |
| url | http://europepmc.org/articles/PMC3352938?pdf=render |
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