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Published on: May 7, 2019
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Antibody-mediated rejection in ABO-incompatible kidney transplantation
Kai Castrezana Lopez1,2, Lukas Weidmann1, Dusan Harmacek1
1Division of Nephrology, University Hospital Zurich, Zurich, Switzerland.
Summary
ABO-incompatible kidney transplants show lower rates of antibody-mediated rejection (AMR) and de novo donor-specific antibodies (DSA). Banff 2022 criteria may overestimate AMR, highlighting the need for molecular diagnostics to differentiate alloimmune injury.
Area of Science:
- Nephrology
- Transplantation Immunology
- Immunopathology
Background:
- C4d deposition in ABO-incompatible (ABOi) kidney transplants suggests accommodation, not rejection.
- Donor-specific antibodies (DSA) targeting blood group antigens A/B are key in ABOi AMR diagnosis.
- Microvascular inflammation (MVI) is a primary diagnostic marker for antibody-mediated rejection (AMR).
Purpose of the Study:
- To evaluate de novo anti-HLA DSA development in ABOi versus ABO-compatible (ABOc) kidney transplant recipients (KTRs).
- To compare Banff 2022 classification with molecular diagnostics (MMDx) for AMR in ABOi KTRs.
- To investigate the role of C4d deposition in driving molecular AMR activity.
Main Methods:
- Analysis of 66 ABOi and 251 ABOc KTRs for anti-HLA DSA.
- Classification of 46 ABOi protocol biopsies using Banff 2022 criteria.
- Assessment of 25 ABOi protocol biopsies with MMDx and comparison to ABOc biopsies across different AMR categories.
Main Results:
- ABOi KTRs exhibited lower rates of de novo anti-HLA DSA and clinical AMR compared to ABOc KTRs.
- MMDx confirmed molecular AMR in only 14% of ABOi biopsies meeting Banff AMR criteria (56%).
- C4d deposition was found to drive molecular AMR activity in ABOc biopsies, even without histological AMR diagnosis.
Conclusions:
- ABOi kidney transplantation is associated with a reduced risk of de novo anti-HLA DSA development.
- Current Banff 2022 criteria may lead to overdiagnosis of AMR in ABOi kidney transplants.
- Molecular diagnostics are crucial for distinguishing alloimmune injury from C4d deposition and assessing AMR accurately.
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