title: ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation.
abstract: Organ transplantation from ABO blood group-incompatible (ABOi) donors requires accurate detection, effective removal and subsequent surveillance of antidonor antibodies. Because ABH antigen subtypes are expressed differently in various cells and organs, measurement of antibodies specific for the antigen subtypes in the graft is essential. Erythrocyte agglutination, the century-old assay used clinically, does not discriminate subtype-specific ABO antibodies and provides limited information on antibody isotypes. We designed and created an ABO-glycan microarray and demonstrated the precise assessment of both the presence and, importantly, the absence of donor-specific antibodies in an international study of pediatric heart transplant patients. Specific IgM, IgG, and IgA isotype antibodies to nonself ABH subtypes were detected in control participants and recipients of ABO-compatible transplants. Conversely, in children who received ABOi transplants, antibodies specific for A subtype II and/or B subtype II antigens-the only ABH antigen subtypes expressed in heart tissue-were absent, demonstrating the fine specificity of B cell tolerance to donor/graft blood group antigens. In contrast to the hemagglutination assay, the ABO-glycan microarray allows detailed characterization of donor-specific antibodies necessary for effective transplant management, representing a major step forward in precise ABO antibody detection.
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Jeyakanthan
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: P J
authors.initials: PJ
authors.lastname: Meloncelli
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: L
authors.initials: L
authors.lastname: Zou
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: T L
authors.initials: TL
authors.lastname: Lowary
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Larsen
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Maier
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Tao
authors.affiliation: Pediatrtic Cardiology, Loma Linda University Medical Center, Loma Linda, CA.
authors.forename: J
authors.initials: J
authors.lastname: Rusch
authors.affiliation: Pediatrtic Cardiology, Loma Linda University Medical Center, Loma Linda, CA.
authors.forename: R
authors.initials: R
authors.lastname: Chinnock
authors.affiliation: Pediatric Cardiology, Great Ormond Street Hospital for Sick Children, London, UK.
authors.forename: N
authors.initials: N
authors.lastname: Shaw
authors.affiliation: Pediatric Cardiology, Great Ormond Street Hospital for Sick Children, London, UK.
authors.forename: M
authors.initials: M
authors.lastname: Burch
authors.affiliation: Division of Pediatric Cardiology, Columbia University, New York, NY.
authors.forename: K
authors.initials: K
authors.lastname: Beddows
authors.affiliation: Division of Pediatric Cardiology, Columbia University, New York, NY.
authors.forename: L
authors.initials: L
authors.lastname: Addonizio
authors.affiliation: Division of Pediatric Cardiology, Columbia University, New York, NY.
authors.forename: W
authors.initials: W
authors.lastname: Zuckerman
authors.affiliation: Pediatric Cardiology, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL.
authors.forename: E
authors.initials: E
authors.lastname: Pahl
authors.affiliation: Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Rutledge
authors.affiliation: Department of Surgery, Emory University School of Medicine, Atlanta, GA.
authors.forename: K R
authors.initials: KR
authors.lastname: Kanter
authors.affiliation: Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: C W
authors.initials: CW
authors.lastname: Cairo
authors.affiliation: National Institute for Nanotechnology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: J M
authors.initials: JM
authors.lastname: Buriak
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.|Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Ross
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.|Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: I
authors.initials: I
authors.lastname: Rebeyka
authors.affiliation: Department of Surgery, University of Alberta, Edmonton, Alberta, Canada.|Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.|Alberta Transplant Institute, University of Alberta, Edmonton, Alberta, Canada.|Department of Medical Microbiology & Immunology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: L J
authors.initials: LJ
authors.lastname: West
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D001787:Blood Group Incompatibility / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007223:Infant; D007231:Infant, Newborn; D007518:Isoantibodies / Q000276:immunology*; D008297:Male; D046228:Microarray Analysis; D011134:Polysaccharides / Q000276:immunology*; D011379:Prognosis
chemical_list: D000017:ABO Blood-Group System; D007518:Isoantibodies; D011134:Polysaccharides