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

Autor: Bentall A; Department of Nephrology, University Hospital, Birmingham, UK.; Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, Minnesota, USA., Jeyakanthan M; Department of Cardiothoracic Surgery, James Cook University Hospital, Middlesbrough, UK.; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada., Braitch M; Department of Nephrology, University Hospital, Birmingham, UK., Cairo CW; Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Lowary TL; Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, Canada., Maier S; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, University of Alberta, Edmonton, AB, Canada., Halpin A; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, University of Alberta, Edmonton, AB, Canada.; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada., Motyka B; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, University of Alberta, Edmonton, AB, Canada., Zou L; Alberta Glycomics Centre and Department of Chemistry, University of Alberta, Edmonton, AB, Canada., West LJ; Department of Pediatrics, University of Alberta, Edmonton, AB, Canada.; Alberta Transplant Institute and Canadian Donation and Transplantation Research Program, University of Alberta, Edmonton, AB, Canada.; Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada.; Department of Surgery, University of Alberta, Edmonton, AB, Canada.; Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, AB, Canada., Ball S; Department of Nephrology, University Hospital, Birmingham, UK.; School of Immunity and Infection, University of Birmingham, Birmingham, UK.
Jazyk: angličtina
Zdroj: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons [Am J Transplant] 2021 Nov; Vol. 21 (11), pp. 3649-3662. Date of Electronic Publication: 2021 Jul 05.
DOI: 10.1111/ajt.16712
Abstrakt: 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.
(© 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.)
Databáze: MEDLINE
Externí odkaz: