IgG Antibody Titres Are Critical in ABO-Incompatible Kidney Transplantation
IgG antibodies are the clinically important antibody type in ABO-incompatible (ABOi) kidney transplantation, while IgM antibodies are not contraindications to transplantation and are not clinically relevant. 1
Why IgG Matters and IgM Does Not
IgG Antibodies Drive Rejection
IgG anti-donor antibodies place the allograft at significant risk for rejection due to reactivation of immune memory, whereas IgM antibodies are associated with much lower rejection risk 1
IgG antibodies detected by sensitive crossmatch methods (AHG-enhanced CDC or flow cytometry) increase the incidence of accelerated and acute rejection episodes 1
Positive B-cell and T-cell crossmatches associated with poor transplant outcomes are specifically due to IgG antibodies, not IgM 1
IgM Antibodies Are Clinically Irrelevant
IgM-positive crossmatches (whether by AHG or flow cytometry) are explicitly NOT contraindications to transplantation 1
IgM antibodies, whether they are auto-antibodies or antibodies directed at HLA class I antigens, do not prevent successful transplantation 1
Guidelines specifically recommend eliminating IgM reactivity by heat or chemical treatment during testing to avoid false-positive results that would incorrectly suggest transplant incompatibility 1
Practical Implications for ABOi Transplantation
Pre-Transplant Desensitization Targets IgG
ABOi transplantation requires pre-transplant reduction of the recipient's IgG isoagglutinin titer against the donor to prevent hyperacute rejection 2
Treatment modalities (plasma exchange, immunoadsorption, or combined approaches) are specifically designed to reduce IgG antibody levels 2, 3
Plasma exchange is approximately twice as effective as immunoadsorption alone for IgG removal, achieving mean reductions of 2.6 titer steps per session versus 1.3 steps 2
Target Antibody Levels
Anti-A and anti-B IgG titres less than 16 are recommended at the time of transplantation 3
IgG titres higher than 128 may be considered a risk factor for rejection in the early post-transplant period 3
Methods used to test for alloantibodies should be sensitive and specifically identify clinically relevant IgG antibodies 1
Post-Transplant Monitoring
Acute antibody-mediated rejection in ABOi transplantation is caused by IgG deposits (specifically anti-ABO IgG antibodies), not IgM 4
Successful treatment of acute rejection requires clearing deposited IgG from the kidney allograft using antigen-specific immunoadsorption 4
The microcolumn gel card test (MGT) can effectively monitor IgG titre changes following surgery 5
Critical Pitfalls to Avoid
Do not delay or cancel ABOi transplantation based solely on elevated IgM titres - these are not clinically relevant contraindications 1
Be aware that commercial IVIG products contain detectable anti-A and anti-B antibodies, which can complicate interpretation of post-treatment antibody titers 6
Always distinguish between IgG and IgM when interpreting crossmatch results, as membrane-dependent assays can detect both antibody types but only IgG predicts clinical outcomes 1
Different antibody detection methods (tube test, microcolumn gel card, glass bead card) can yield titre results that differ by 2-4 serial dilution steps, so use consistent methodology for a given patient 5