ABH-Glycan Microarray Characterizes ABO Subtype Antibodies: Fine Specificity of Immune Tolerance After ABO-Incompatible Transplantation

Abstract

Organ transplantation from ABO blood groupincompatible (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.

Clinical outcomes with ABO antibody titer variability in a multicenter study of ABO‐incompatible kidney transplantation in the United Kingdom

“…This also may be compounded by greater expression of A antigen compared with B antigen on the vascular endothelium due to greater efficiency of the A transferases, resulting in greater numbers of targets for anti‐A versus anti‐B. Recent work has demonstrated a different type of chain binding in ABOi cardiac transplantation that differentiates between vascular endothelium and red cell type chain expression . These data support the requirement for appropriately assessing anti‐A/anti‐B with respect to the type of chain‐specific binding for managing patients effectively and reducing the risk in unnecessary therapies.…”

ABO-incompatible heart transplantation

“…Reliance on inaccurate agglutination assays may result in unnecessary exclusion of consideration of patients for ABOi transplantation or in performance of antibody removal procedures that may not be needed. A recently developed ABH-glycan microarray assay that fully characterizes and quantifies serum ABO antibodies towards the ABH antigens actually expressed on the graft will generate more precise information for effective clinical management 40 . The ABH-microarray and additional glycomics-based tools will also allow further investigation of the immunobiology of the ABO system and its impact in organ transplantation, including mechanisms of immunity, tolerance and accommodation 41 .…”

Current state of transfusion practices for ABO‐incompatible pediatric heart transplant patients in the United States and Canada

“…Other current studies would suggest RBCs may not be an optimal target when assessing anti‐A and anti‐B levels in potential transplant recipients due to differences in the subtypes of A and B antigen structures expressed on RBCs versus transplanted organs . As a result, glycan microarray platforms populated with the specific A and B determinants more likely expressed on transplanted organs may be more accurate to define the level of clinically relevant ABO IH in the transplant setting . However, caution will need to be used in interpreting results from solid‐phase assays, as the presentation and types of antigens on these surfaces do not always equate with the specificity, affinity, and avidity that would be observed on natural tissues .…”