title: Early acute antibody-mediated rejection of a negative flow crossmatch 3rd kidney transplant with exclusive disparity at HLA-DP.
abstract: Donor-specific alloantibodies (DSA) to HLA-DP may cause antibody-mediated rejection (AMR), especially in re-transplants. We describe the immunization history of a patient who received 3 kidney transplants; the 3rd kidney was completely matched except at DPA1 and DPB1. Prior to the 3rd transplant, single antigen bead analysis (SAB) showed DSA reactivity against DPA1 shared by the 1st and 3rd donors, but B and T flow crossmatch (FXM) results were negative. Within 11 days the 3rd transplant underwent acute C4d+ AMR which coincided with the presence of complement (C1q)-binding IgG1 DSA against donor DPA1 and DPB1. Using HLAMatchmaker and SAB, we provide evidence that eplet (epitope) spreading on DPA1 and eplet sharing on differing DPB1 alleles of the 1st and 3rd transplants was associated with AMR. Since weak DSA to DPA1/DPB1 may induce acute AMR with negative FXM, donor DPA1/DPB1 high resolution typing should be considered in sensitized patients with DP-directed DSA.
authors.affiliation: Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Beata
authors.initials: B
authors.lastname: Mierzejewska
authors.affiliation: Department of Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Schroder
authors.affiliation: Department of Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Caitlin E
authors.initials: CE
authors.lastname: Baum
authors.affiliation: Department of Pathology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Annette
authors.initials: A
authors.lastname: Blair
authors.affiliation: Department of Pathology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Connie
authors.initials: C
authors.lastname: Smith
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Rene J
authors.initials: RJ
authors.lastname: Duquesnoy
authors.affiliation: Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, PA 15213, USA.
authors.forename: Marilyn
authors.initials: M
authors.lastname: Marrari
authors.affiliation: Department of Pathology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Amira
authors.initials: A
authors.lastname: Gohara
authors.affiliation: Department of Internal Medicine, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Deepak
authors.initials: D
authors.lastname: Malhotra
authors.affiliation: Department of Internal Medicine, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Dinkar
authors.initials: D
authors.lastname: Kaw
authors.affiliation: HLA Typing Laboratory, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Liwski
authors.affiliation: Department of Urology, University of Toledo College of Medicine, Toledo, OH 43614, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rees
authors.affiliation: Department of Microbiology and Immunology, University of Toledo College of Medicine, Toledo, OH 43614, USA. Electronic address: stanislaw.stepkowski@utoledo.edu.
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Stepkowski
mesh_terms: D015922:Complement C1q / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D006682:HLA-DP Antigens / Q000276:immunology*; D059867:HLA-DP alpha-Chains / Q000276:immunology*; D059868:HLA-DP beta-Chains / Q000276:immunology; D059826:HLA-DRB3 Chains / Q000276:immunology; D006650:Histocompatibility Testing; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis*; D007668:Kidney / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D016030:Kidney Transplantation; D010446:Peptide Fragments / Q000378:metabolism; D061349:Unrelated Donors; D055815:Young Adult
chemical_list: D006682:HLA-DP Antigens; D059867:HLA-DP alpha-Chains; D059868:HLA-DP beta-Chains; C071172:HLA-DPA1 antigen; C071170:HLA-DPB1 antigen; D059826:HLA-DRB3 Chains; D007518:Isoantibodies; D010446:Peptide Fragments; D015922:Complement C1q; D015935:Complement C4b; C032261:complement C4d
keywords: Antibody-mediated rejection; Donor-specific antibodies; Epitopes; Flow cytometry crossmatch; Kidney transplantation
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