title: HLA-G*01:04∼UTR3 Recipient Correlates With Lower Survival and Higher Frequency of Chronic Rejection After Lung Transplantation.
abstract: Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. Soluble HLA-G (sHLA-G) has been associated with increased graft survival and decreased rejection episodes in solid organ transplantation. HLA-G haplotypes named UTRs, defined by SNPs from both the 5'URR and 3'UTR, have been reported to reliably predict sHLA-G level. The aim of this retrospective study was to determine the impact of HLA-G alleles and UTR polymorphism from LTx recipients on anti-HLA allo-immunization risk, overall survival and chronic rejection (CLAD). HLA-G SNPs were genotyped in 124 recipients who underwent LTx from 1996 to 2010 in Marseille, 123 healthy individuals and 26 cystic fibrosis patients not requiring LTx. sHLA-G levels were measured for 38 LTx patients at D0, M3 and M12 and for 123 healthy donors. HLA-G*01:06∼UTR2 was associated with a worse evolution of cystic fibrosis (p = 0.005) but not of long-term survival post-LTx. HLA-G*01:04∼UTR3 haplotype was associated with lower levels of sHLA-G at D0 and M3 (p = 0.03), impaired long-term survival (p = 0.001), increased CLAD occurrence (p = 0.03) and the production of de novo donor-specific antibodies (DSA) at M3 (p = 0.01). This study is the first to show the deleterious association of different HLA-G alleles and UTRs in LTx.
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Di Cristofaro
authors.affiliation: Service de Pneumologie et Transplantation Pulmonaire, CHU Nord Faculté de Médecine, URMITE - CNRS-UMR 6236, Aix Marseille Université, Marseille, France.
authors.forename: M
authors.initials: M
authors.lastname: Reynaud-Gaubert
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.
authors.forename: F
authors.initials: F
authors.lastname: Carlini
authors.affiliation: Inserm U491, Génétique Médicale et Développement, Aix-Marseille Université, Faculté de Médecine, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Roubertoux
authors.affiliation: Department of Public Health -EA 3279 Research Unit, University Hospital Marseille, Aix-Marseille University, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Loundou
authors.affiliation: Immunogenetics laboratory, EFS-Alpes Méditerranée, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Basire
authors.affiliation: Immunogenetics laboratory, EFS-Alpes Méditerranée, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Frassati
authors.affiliation: Service de Chirurgie Thoracique, Hôpital Nord, Marseille, France.
authors.forename: P
authors.initials: P
authors.lastname: Thomas
authors.affiliation: Service de Pneumologie et Transplantation Pulmonaire, CHU Nord Faculté de Médecine, URMITE - CNRS-UMR 6236, Aix Marseille Université, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Gomez
authors.affiliation: Aix-Marseille Université, CNRS, EFS, ADES UMR 7268, Marseille, France.|Immunogenetics laboratory, EFS-Alpes Méditerranée, Marseille, France.
authors.forename: C
authors.initials: C
authors.lastname: Picard
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics*; D000328:Adult; D002908:Chronic Disease; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000453:epidemiology*; D006085:Graft Survival / Q000502:physiology*; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008171:Lung Diseases / Q000401:mortality / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
chemical_list: D020413:3' Untranslated Regions; D059951:HLA-G Antigens
keywords: Bronchiolitis obliterans (BOS); function/dysfunction; genetics; immune regulation; lung (allograft); rejection: antibody-mediated (ABMR)