Characterization of ABH-subtype donor-specific antibodies in ABO-A-incompatible kidney transplantation

Andrew Bentall, Mylvaganam Jeyakanthan, Manjit Braitch, Christopher W. Cairo, Todd L. Lowary, Stephanie Maier, Anne Halpin, Bruce Motyka, Lu Zou, Lori J. West, Simon Ball

Research output: Contribution to journalArticlepeer-review


ABO-incompatible (ABOi) transplantation requires preemptive antibody reduction; however, the relationship between antibody-mediated rejection (AMR) and ABO-antibodies, quantified by hemagglutination (HA), is inconsistent, possibly reflecting variable graft resistance to AMR or HA assay limitations. Using an ABH-glycan microarray, we quantified ABO-A antigen-subtype (A-subtype)-specific IgM and IgG in 53 ABO-O recipients of ABO-A kidneys, before and after antibody removal (therapeutic plasma exchange [TPE] or ABO-A-trisaccharide immunoadsorption [IA]) and 1-year posttransplant. IgM binding to all A-subtypes correlated highly (R2 ≥.90) and A-subtype antibody specificities was reduced equally by IA versus TPE. IgG binding to the A-subtypes (II–IV) expressed in kidney correlated poorly (.27 ≤ R2 ≤.69). Reduction of IgG specific to A-subtype-II was equivalent for IA and TPE, whereas IgG specific to A-subtypes-III/IV was not as greatly reduced by IA (p <.005). One-year posttransplant, IgG specific to A-II remained the most reduced antibody. Immunostaining revealed only A-II on vascular endothelium but A-subtypes II-III/IV on tubular epithelium. These results show that ABO-A-trisaccharide is sufficient for IgM binding to all A-subtypes; this is true for IgG binding to A-II, but not subtypes-III/IV, which exhibits varying degrees of specificity. We identify A-II as the major, but importantly not the sole, antigen relevant to treatment and immune modulation in adult ABO-A-incompatible kidney transplantation.

Original languageEnglish (US)
Pages (from-to)3649-3662
Number of pages14
JournalAmerican Journal of Transplantation
Issue number11
StatePublished - Nov 2021


  • ABO incompatibility
  • antibody biology
  • antigen biology
  • clinical research/practice
  • glycomics
  • histocompatibility
  • kidney transplantation/nephrology
  • translational research/science

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


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