What is the target anti-A antibody titre (IgM) level to minimize the risk of antibody-mediated rejection in ABO-incompatible liver transplant patients?

Anti-A Antibody Titre IgM Level Cut-offs for ABO-Incompatible Liver Transplantation

For ABO-incompatible liver transplantation, anti-A antibody IgM titers should be maintained at ≤1:8 to minimize the risk of antibody-mediated rejection. 1

Background and Importance

ABO-incompatible liver transplantation has become an important strategy to expand the donor pool, potentially increasing available donors by 25-35% 1. However, without proper management of antibody titers, these transplants carry significant risk of antibody-mediated rejection (AMR) that can lead to graft loss.

Target Antibody Titer Levels

• Pre-transplant anti-A antibody titers should be reduced to ≤1:16 for IgG and ≤1:8 for IgM to minimize the risk of antibody-mediated rejection 1
• Post-transplant monitoring should aim to maintain these levels, especially during the first two weeks after transplantation when the risk of AMR is highest 2
• Patients with high pre-transplant titers (even as high as 1:4096) can still achieve good outcomes with appropriate desensitization protocols 3

Desensitization Protocol Components

Pre-transplant Desensitization

• Rituximab (anti-CD20 monoclonal antibody) administration:
  • Typically given 2-4 weeks before transplantation at 375 mg/m² 1, 4
  • Some protocols use a second dose (300 mg) one day before transplantation for patients with very high titers 3
• Plasmapheresis:
  • Double-filtration plasmapheresis (4-7 sessions) to achieve target antibody titers 1
  • Antigen-specific immunoadsorption may be used as an alternative or adjunct to conventional plasmapheresis 2
• Mycophenolate mofetil:
  • Should be started 7 days prior to transplantation to suppress B-cell function 1

Post-transplant Management

• Immunosuppressive regimen:
  • Quadruple immunosuppression with tacrolimus, mycophenolate mofetil, corticosteroids, and basiliximab induction 4
  • Tacrolimus trough levels should be kept at 6-10 ng/ml during the first month followed by 4-8 ng/ml thereafter 5
• Intravenous immunoglobulin (IVIG):
  • Administer 0.4 g/kg per day for 10 consecutive days after transplantation 4
• Regular monitoring of anti-A antibody titers:
  • More frequent monitoring in the first two weeks post-transplant 2
  • Additional plasmapheresis may be required if titers rise above target levels 2

Special Considerations

• Blood group A2 donors require special attention as they may still trigger antibody-mediated rejection in type B recipients despite lower A antigen expression 6
• Splenectomy may be considered as a rescue therapy in cases of refractory antibody-mediated rejection 6
• Screening for preformed donor-specific antibodies (DSAs) should be performed in recipients at risk of humoral sensitization (previous transplantation, previous transfusions, previous pregnancies) 5
• Patients with high levels of preformed DSAs should receive more intensive follow-up than those without detectable pre-formed DSAs 5

Monitoring for Rejection

• Regular liver function tests to detect early signs of graft dysfunction 2
• Liver biopsy should be performed if antibody-mediated rejection is suspected 5
• Treatment of established antibody-mediated rejection may include:
  • Plasmapheresis with intravenous immunoglobulin 5
  • Second-line therapies such as rituximab or eculizumab for persistent AMR 5

By maintaining anti-A antibody IgM titers ≤1:8 through appropriate desensitization protocols and immunosuppression, ABO-incompatible liver transplantation can achieve outcomes comparable to ABO-compatible transplantation 4.