TY - JOUR
T1 - Characterization of ABH-subtype donor-specific antibodies in ABO-A-incompatible kidney transplantation
AU - Bentall, Andrew
AU - Jeyakanthan, Mylvaganam
AU - Braitch, Manjit
AU - Cairo, Christopher W.
AU - Lowary, Todd L.
AU - Maier, Stephanie
AU - Halpin, Anne
AU - Motyka, Bruce
AU - Zou, Lu
AU - West, Lori J.
AU - Ball, Simon
N1 - Publisher Copyright:
© 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - ABO incompatibility
KW - antibody biology
KW - antigen biology
KW - clinical research/practice
KW - glycomics
KW - histocompatibility
KW - kidney transplantation/nephrology
KW - translational research/science
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U2 - 10.1111/ajt.16712
DO - 10.1111/ajt.16712
M3 - Article
C2 - 34101982
AN - SCOPUS:85109154136
SN - 1600-6135
VL - 21
SP - 3649
EP - 3662
JO - American Journal of Transplantation
JF - American Journal of Transplantation
IS - 11
ER -