title: Donor-specific antibody to trans-encoded donor HLA-DQ heterodimer.
abstract: The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans-encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans-heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6±3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2.5 (DQB1*02, DQA1*05), DQ2.3 (DQB1*02, DQA1*03), and DQ4.3 (DQB1*04, DQA1*03). Two of them eventually lost grafts (2 and 5years later) with allograft nephropathy. In conclusion, post-transplant patients may develop DSA to donor DQ trans-heterodimers. Further studies are warranted to determine the clinical significance of such DSAs.
authors.affiliation: HLA Laboratory, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Dennis F
authors.initials: DF
authors.lastname: Habig
authors.affiliation: HLA Laboratory, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Justine L
authors.initials: JL
authors.lastname: Gaspari
authors.affiliation: HLA Laboratory, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Parvez M
authors.initials: PM
authors.lastname: Lokhandwala
authors.affiliation: HLA Laboratory, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Domen
authors.affiliation: Anatomic Pathology, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Abendroth
authors.affiliation: Division of Transplantation, Department of Surgery, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Zakiyah
authors.initials: Z
authors.lastname: Kadry
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Nasrollah
authors.initials: N
authors.lastname: Ghahramani
authors.affiliation: Division of Transplantation, Department of Surgery, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Riaz Ali
authors.initials: RA
authors.lastname: Shah
authors.affiliation: Division of Transplantation, Department of Surgery, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States.
authors.forename: Ashokkumar
authors.initials: A
authors.lastname: Jain
authors.affiliation: HLA Laboratory, Department of Pathology, Penn State University College of Medicine, Penn State Milton S. Hershey Medical Center, 500 University Drive, Hershey, PA 17033, United States. Electronic address: hshike@hmc.psu.edu.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Shike
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D000918:Antibody Specificity / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D006680:HLA Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000276:immunology*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D055503:Protein Multimerization; D012189:Retrospective Studies; D014019:Tissue Donors; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D006683:HLA-DQ Antigens; D007518:Isoantibodies
keywords: Antibody-mediated rejection; C1q assay; Kidney transplantation; Solid phase assay