title: Lung intragraft donor-specific antibodies as a risk factor for graft loss.
abstract: The effect of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSAs) on graft survival is recognized in lung transplantation, but not all serum DSAs appear to be harmful. We wondered whether in situ DSA detection from graft biopsy specimens could help in identifying lung transplant recipients (LTRs) at higher risk for graft loss.
  
  
  
  Class I and II HLA antibody single-antigen flow bead assays were performed in 53 LTRs to identify immunoglobulin G DSA in biopsy specimen eluates and in sera and to evaluate C1q binding ability of DSA in sera. Intragraft DSAs (gDSAs) were correlated with serum DSAs (sDSAs), clinical and histologic data, and graft survival.
  
  
  
  Twenty-eight (52.8%) LTRs had sDSAs, 12 (22.6%) had C1q-positive sDSAs, and 11 (20.8%) had gDSAs. Fifty sDSAs were found, among which 15 (30%) were C1q-positive and 14 (28%) were found in biopsy specimen eluates. One DSA was detected in the biopsy specimen only. Serum mean fluorescence intensity and biopsy fragment size were higher for sDSAs detected in biopsy specimens (p = 0.003 and p = 0.02, respectively). One-year post-biopsy graft survival was lower for LTRs with gDSAs (p = 0.008 by log-rank test). Presence of gDSA at the time of biopsy constituted a risk factor for graft loss in univariate (odds ratio, 6.67; 95% confidence interval [CI] 1.51-29.47; p = 0.008; hazard risk, 3.44; 95% CI, 1.47-8.01, p = 0.005) and multivariate (odds ratio, 5.85; 95% CI, 1.23-27.68; p = 0.03; hazard risk, 4.51; 95% CI, 1.83-11.13; p = 0001) analyses using logistic regression and a Cox proportional hazard model, respectively.
  
  
  
  In lung transplantation, gDSA appears to be a valuable biomarker to identify pathogenic DSA and LTRs with a higher risk for graft loss.
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Visentin
authors.affiliation: Service des Maladies Respiratoires, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
authors.forename: Albane
authors.initials: A
authors.lastname: Chartier
authors.affiliation: Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France.
authors.forename: Layal
authors.initials: L
authors.lastname: Massara
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Linares
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Guidicelli
authors.affiliation: Service des Maladies Respiratoires, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Blanchard
authors.affiliation: Laboratoire de Biologie et Pathologie des Tumeurs, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France; Département de Pathologie, A2406, Université de Bordeaux, Bordeaux, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Parrens
authors.affiliation: Laboratoire de Biologie et Pathologie des Tumeurs, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
authors.forename: Hugues
authors.initials: H
authors.lastname: Begueret
authors.affiliation: Service des Maladies Respiratoires, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Pessac, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Dromer
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France; Unité Mixte de Recherche 5164, Centre National de la Recherche Scientifique, Université de Bordeaux, Talence, France. Electronic address: jean-luc.taupin@aphp.fr.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
mesh_terms: D000906:Antibodies; D006084:Graft Rejection; D006085:Graft Survival; D006680:HLA Antigens; D006801:Humans; D007518:Isoantibodies; D016030:Kidney Transplantation; D016040:Lung Transplantation; D012307:Risk Factors; D014019:Tissue Donors
chemical_list: D000906:Antibodies; D006680:HLA Antigens; D007518:Isoantibodies
keywords: HLA antibodies; antibody-mediated rejection; biopsy; lung transplant; single-antigen flow beads