title: Deciphering allogeneic antibody response against native and denatured HLA epitopes in organ transplantation.
abstract: Anti-HLA donor-specific antibodies are deleterious for organ transplant survival. Class I HLA donor-specific antibodies are identified by using the Luminex single antigen beads (LSAB) assay, which also detects anti-denatured HLA antibodies (anti-dHLAs). Anti-dHLAs are thought to be unable to recognize native HLA (nHLA) on the cell surface and therefore to be clinically irrelevant. Acid denaturation of nHLA on LSAB allows anti-dHLAs to be discriminated from anti-nHLAs. We previously defined a threshold for the ratio between mean fluorescence intensity against acid-treated (D for denaturation) and nontreated (N) LSAB, D ≥ 1.2 N identifying the anti-dHLAs. However, some anti-dHLAs remained able to bind nHLA on lymphocytes in flow cytometry crossmatches, and some anti-nHLAs conserved significant reactivity toward acid-treated LSAB. After depleting serum anti-nHLA reactivity with HLA-typed cells, we analyzed the residual LSAB reactivity toward nontreated and acid-treated LSABs, and then evaluated the ability of antibodies to recognize nHLA alleles individually. We observed that sera can contain mixtures of anti-nHLAs and anti-dHLAs, or anti-nHLAs recognizing acid-resistant epitopes, all possibly targeting the same allele(s). Therefore, the anti-HLA antibody response can be highly complex and subtle, as is the accurate identification of pathogenic anti-HLA antibodies in human serum.
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.|UMR 5164 CNRS, Université de Bordeaux, Talence, France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Visentin
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.
authors.forename: Gwendaline
authors.initials: G
authors.lastname: Guidicelli
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.|UMR 5164 CNRS, Université de Bordeaux, Talence, France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Moreau
authors.affiliation: One Lambda, Inc, Canoga Park, CA, USA.
authors.forename: Jar-How
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Laboratoire d'Immunologie et Immunogénétique, Hôpital Pellegrin, CHU de Bordeaux, Bordeaux, France.|UMR 5164 CNRS, Université de Bordeaux, Talence, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Taupin
mesh_terms: D064591:Allografts / Q000276:immunology*; D000906:Antibodies / Q000276:immunology; D000939:Epitopes / Q000276:immunology; D005434:Flow Cytometry; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D016377:Organ Transplantation; D014181:Transplantation Immunology / Q000276:immunology*
chemical_list: D000906:Antibodies; D000939:Epitopes; D015395:Histocompatibility Antigens Class I
keywords: Anti-denatured HLA antibodies; HLA antibodies; HLA epitopes; Luminex single antigen bead assay