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

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 (R (2) ≥ .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 ≤ R (2) ≤ .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.