title: Denatured class I human leukocyte antigen antibodies in sensitized kidney recipients: prevalence, relevance, and impact on organ allocation.
abstract: BACKGROUND
  Single antigen flow beads assays may overestimate sensitization because of the detection of supposedly irrelevant antibodies recognizing denatured class I human leukocyte antigens (HLAs).
  
  
  METHODS
  Sera of 323 HLA-sensitized kidney transplant candidates positive with a class I HLA single antigen flow beads assay were retested after acid treatment of the beads. Denatured HLA antibodies were identified according to ratio between the measured fluorescence intensity for treated and nontreated beads. T-lymphocyte flow cytometry crossmatches were performed to characterize the ability of these antibodies to recognize HLA on normal cells as a surrogate of their potential clinical relevance. Their impact on organ allocation was evaluated through a calculated panel reactive antibody. The utility of single antigen flow beads largely devoid of denatured HLA (iBeads) was also evaluated.
  
  
  RESULTS
  Denatured HLA antibodies were detected in 39% of the patients. They provided much less positive flow cytometry crossmatches than anti-native HLA antibodies (16% vs. 83%, P<0.0001). Removing the HLA-A and HLA-B antigens targeted by denatured HLA antibodies from unacceptable antigens lowered the calculated panel reactive antibody for 90 patients, sometimes dramatically. The iBeads assay demonstrated nearly the same ability to predict crossmatch results than the acid treatment assay.
  
  
  CONCLUSIONS
  Denatured class I HLA antibodies are common, but the antigens they target should not be considered as unacceptable in most cases, because they negatively impact access to a transplant while predominantly providing negative sensitive crossmatches. The iBeads assay seems to be a valuable alternative to better define unacceptable antigens.
authors.affiliation: 1 Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France. 2 UMR CNRS 5164, Université de Bordeaux, Bordeaux, France. 3 Agence de la Biomédecine, Saint-Denis La Plaine, France. 4 One Lambda, Inc., Canoga Park, CA. 5 Laboratoire d'histocompatibilité, Etablissement Français du Sang, Lyon, France. 6 Service de Néphrologie, Transplantation, Dialyse, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France. 7 Address correspondence to: Jean-Luc Taupin, Pharm.D., Ph.D., Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Place Amélie Raba Léon, 33076 Bordeaux Cedex, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Visentin
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Guidicelli
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelet
authors.forename: Christian
authors.initials: C
authors.lastname: Jacquelinet
authors.forename: Benoît
authors.initials: B
authors.lastname: Audry
authors.forename: Thoa
authors.initials: T
authors.lastname: Nong
authors.forename: Valérie
authors.initials: V
authors.lastname: Dubois
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.forename: Jar-How
authors.initials: JH
authors.lastname: Lee
authors.forename: Lionel
authors.initials: L
authors.lastname: Couzi
authors.forename: Pierre
authors.initials: P
authors.lastname: Merville
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood / Q000276:immunology / Q000601:surgery*; D000483:Alleles; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000737:chemistry; D005260:Female; D005434:Flow Cytometry; D005453:Fluorescence; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000097:blood; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D015995:Prevalence; D012189:Retrospective Studies; D009927:Tissue and Organ Procurement / Q000379:methods
chemical_list: D000906:Antibodies; D000941:Antigens; D015395:Histocompatibility Antigens Class I; D007518:Isoantibodies