From the Guidelines
Rebound in ABO-incompatible solid organ transplantation is primarily managed through intensified plasmapheresis or immunoadsorption, alongside optimized immunosuppression, to prevent graft loss due to antibody-mediated rejection. The mechanism of rebound involves the rapid rise of antibody titers after initial reduction, typically occurring 1-2 weeks post-transplant when immunosuppression is reduced, as antibody production temporarily outpaces removal strategies 1. This phenomenon threatens graft survival and necessitates close monitoring of anti-blood group antibody titers and prompt intervention upon detection of rising titers.
Key aspects of management include:
- Intensified plasmapheresis or immunoadsorption to physically remove antibodies, performed daily until titers decrease to safe levels (usually below 1:8 or 1:16) 1.
- Additional immunosuppression with agents like rituximab, intravenous immunoglobulin (IVIG), or bortezomib to suppress antibody production.
- Optimization of maintenance immunosuppression, often involving higher tacrolimus trough levels, mycophenolate mofetil, and corticosteroids.
The biological basis for rebound highlights the importance of both antibody removal and suppression of new antibody production, involving memory B cells and plasma cells that continue producing antibodies despite initial depletion therapies 1. Recent guidelines, such as those from the European Association for the Study of the Liver (EASL), emphasize the importance of tailored immunosuppressive regimens and lifestyle modifications to improve outcomes in solid organ transplant recipients, although these are more broadly applicable and not specifically focused on ABO-incompatible transplantation 1.
From the Research
Mechanism of Rebound in ABO-Incompatible Solid Organ Transplantation
The mechanism of rebound in ABO-incompatible solid organ transplantation refers to the rapid increase in isoagglutinin titers after immunosuppressive treatment or immunoadsorption 2. This rebound effect can lead to humoral rejection, which is a significant concern in ABO-incompatible transplantation.
Factors Contributing to Rebound
Several factors contribute to the rebound effect, including:
- The strength of the immune response against the ABO antigens 3
- The effectiveness of the immunosuppressive regimen 4
- The use of antigen-specific immunoadsorption 2
Management of Rebound
To manage the rebound effect, various strategies are employed, including:
- Desensitization protocols to remove antibodies and prevent their rebound after transplantation 3
- The use of rituximab to deplete B cells and reduce antibody production [(4,2)]
- Tailored desensitization approaches to avoid excessive immunosuppression 3
- The use of intravenous immunoglobulin (IVIG) to reduce the risk of infections 4
Outcomes of ABO-Incompatible Transplantation
Despite the challenges posed by the rebound effect, ABO-incompatible transplantation has been shown to have outcomes similar to those of standard transplantation [(3,5)]. The use of ABO-incompatible grafts can help alleviate the shortage of organs and decrease waitlist times and associated morbidity 5.