From the Guidelines
Intravenous immunoglobulin (IVIG) administration in ABO-incompatible (ABOI) kidney transplantation does not typically increase isohemagglutinin titers and is used to reduce these antibody levels. IVIG works through multiple immunomodulatory mechanisms, including neutralization of circulating antibodies, inhibition of complement activation, and modulation of B and T cell function, as described in the study by 1. In ABOI kidney transplantation protocols, IVIG is commonly administered alongside other desensitization strategies such as plasmapheresis, immunoadsorption, and rituximab to decrease donor-specific blood group antibodies (isohemagglutinins) before transplantation.
Key Points
- The typical IVIG dose ranges from 0.1-0.5 g/kg in low-dose protocols to 1-2 g/kg in high-dose protocols, often given after plasmapheresis sessions to prevent antibody rebound.
- While rare cases of paradoxical increases in antibody titers have been reported with IVIG in other contexts, this is not typically observed in ABOI transplantation when IVIG is used as part of a comprehensive desensitization protocol, as shown in the study by 1.
- Regular monitoring of isohemagglutinin titers is essential throughout the desensitization process and post-transplant period to ensure antibody levels remain at safe thresholds.
Mechanism of Action
IVIG contains anti-idiotypic antibodies that inhibit HLA-specific alloantibodies in vitro and in vivo, as described in the study by 1. The main immune effects of IVIg can likely be accounted for by blockade of Fc-γ receptors, inhibition of the complement system, neutralization of autoantibodies and cytokines, and downregulation of the B-cell receptor.
Clinical Implications
The use of IVIG in ABOI kidney transplantation has been shown to be effective in reducing isohemagglutinin titers and improving patient outcomes, as described in the study by 1. Therefore, IVIG should be considered a valuable component of desensitization protocols in ABOI kidney transplantation.
From the Research
Isohemagglutinin Levels Following IVIG in ABO-Incompatible Kidney Transplant
- Isohemagglutinin levels can be affected by IVIG administration in ABO-incompatible kidney transplant patients 2
- Commercial IVIG products contain detectable anti-A and anti-B antibodies, which can complicate the interpretation of antibody titers in ABO-incompatible transplantation 2
- The use of IVIG in ABO-incompatible kidney transplant patients may lead to an increase in isohemagglutinin levels due to the presence of anti-A and anti-B antibodies in the IVIG preparation 2
Factors Influencing Isohemagglutinin Titers
- High initial isoagglutinin titer, low titer-reduction rate, short interval between rituximab and first plasmapheresis, and blood group O are predictors of titer-rebound after transplant 3
- The change in isoagglutinin titer-rebound was not significant with low-dose rituximab, and the infection rate was significantly decreased 3
Clinical Outcomes and Isohemagglutinin Titers
- ABO-incompatible kidney transplantation can be successfully conducted by monitoring IgM isoagglutinin titers during desensitization 4
- Patients with high pre-KT IgG isoagglutinin titers had equally successful outcomes as those with low IgG titers, as long as the pre-KT IgM isoagglutinin titer was reduced to 4 or less 4
- High-dose IVIG may reduce the risk of infections in ABO-incompatible kidney transplant patients 5