title: HLA-E(⁎)01:03 Allele in Lung Transplant Recipients Correlates with Higher Chronic Lung Allograft Dysfunction Occurrence.
abstract: Lung transplantation (LTx) is a valid therapeutic option for selected patients with end-stage lung disease. HLA-E seems to play a major role in the immune response to different viral infections and to affect transplantation outcome, in Hematopoietic Stem Cell Transplantation, for example. Two nonsynonymous alleles, HLA-E(⁎)01:01 and HLA-E(⁎)01:03, have functional differences, involving relative peptide affinity, cell surface expression, and potential lytic activity of NK cells. The aim of this retrospective study was to determine the impact of these two alleles for LTx recipients on anti-HLA alloimmunization risk, overall survival, and chronic rejection (CLAD). HLA-E was genotyped in 119 recipients who underwent LTx from 1998 to 2010 in a single transplantation center. In univariate analysis, both HLA-E homozygous states were associated with impaired overall survival compared to heterozygous HLA-E alleles (p = 0.01). In multivariate analysis, HLA-E(⁎)01:03 allele showed increased CLAD occurrence when compared to homozygous HLA-E(⁎)01:01 status (HR: 3.563 (CI 95%, 1.016-12), p = 0.047). HLA-E allele did not affect pathogen infection or the production of de novo DSA. This retrospective study shows an uninvestigated, deleterious association of HLA-E alleles with LTx and requires verification using a larger cohort.
authors: CNRS, EFS, ADES UMR 7268, Aix-Marseille Université, 13916 Marseille, France.
authors: Julie
authors: J
authors: Di Cristofaro
authors: Immunogenetics Laboratory, EFS-Alpes Méditerranée, 13005 Marseille, France.
authors: Mathieu
authors: 0000-0002-1318-3956
authors: M
authors: Pelardy
authors: Department of Public Health, EA 3279 Research Unit, Marseille University Hospital, Aix-Marseille University, Marseille, France.
authors: Anderson
authors: 0000-0003-4301-9476
authors: A
authors: Loundou
authors: Immunogenetics Laboratory, EFS-Alpes Méditerranée, 13005 Marseille, France.
authors: Agnès
authors: A
authors: Basire
authors: Service de Pneumologie, Hôpital Nord, 13015 Marseille, France.
authors: Carine
authors: C
authors: Gomez
authors: CNRS, EFS, ADES UMR 7268, Aix-Marseille Université, 13916 Marseille, France.
authors: Jacques
authors: J
authors: Chiaroni
authors: Service de Chirurgie Thoracique, Hôpital Nord, 13015 Marseille, France.
authors: Pascal
authors: P
authors: Thomas
authors: Service de Pneumologie, Hôpital Nord, 13015 Marseille, France.
authors: Martine
authors: M
authors: Reynaud-Gaubert
authors: CNRS, EFS, ADES UMR 7268, Aix-Marseille Université, 13916 Marseille, France; Immunogenetics Laboratory, EFS-Alpes Méditerranée, 13005 Marseille, France.
authors: Christophe
authors: 0000-0001-9118-5239
authors: C
authors: Picard
mesh_terms: D000328:Adult; D000483:Alleles; D064591:Allografts / Q000276:immunology* / Q000378:metabolism*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006084:Graft Rejection; D006085:Graft Survival; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D066027:Transplant Recipients; D055815:Young Adult; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens