From the Guidelines
IgG antibodies to HLA antigens are considered in a cadaveric donor.
Key Considerations
- The presence of IgG antibodies to HLA antigens is a contraindication to transplantation, as it can lead to hyperacute and/or accelerated rejection 1.
- The crossmatch identifies recipient anti-donor reactivity that is associated with a poor clinical outcome, and it is necessary to test patient sera for the presence of antibodies to HLA antigens and use these reactive sera in the recipient-donor crossmatch 1.
- Methods used to test for the presence of alloantibodies should be sensitive and identify clinically relevant IgG antibodies to HLA antigens, such as flow cytometry or a complement-dependent cytotoxicity (CDC) assay 1.
- A positive flow cytometry or AHG-CDC crossmatch against either T cell or B cell donor targets, using sera with IgG antibodies to HLA antigens, is a contraindication to transplantation 1.
- More recent evidence suggests that HLA-DQ mismatches are associated with a higher risk of de novo DSA development and graft rejection, and minimizing the likelihood of developing HLA-DQ DSA is likely to translate into significant clinical benefit after kidney transplantation 1.
Testing for Antibodies
- The historically highest PRA, current, and pretransplant sera should be used in a donor-specific crossmatch to prevent hyperacute and/or accelerated rejection 1.
- Newer assays, such as ELISA and Flow Bead, can detect IgG antibodies to HLA antigens and are more predictive of posttransplant acute rejection and graft loss than membrane-dependent assays 1.
- The Flow Bead PRA procedure can detect IgG antibody to HLA antigens in sera that are reported to be non-reactive by ELISA, and is a significant risk factor for post-transplant rejection 1.
From the Research
Antibodies Considered in Cadaveric Donor
The following antibodies are considered in a cadaveric donor:
- Human leukocyte antigen (HLA) molecules, which may be directed against HLA class I or/and class II antigens 2
- Donor-specific antibodies (DSAs) detectable by flow cytometry (FC) or solid phase assays (SPA) 3
- Panel reactive antibodies (PRA) which are measured by enzyme-linked immunosorbent assay (ELISA) 2, 4
- Anti-HLA antibodies, which can be detected by CDC, FC, or SPA 3, 4
Factors Influencing Antibody Levels
Several factors can influence antibody levels in cadaveric donors, including:
- Patient reactivity to antigen stimulation, which is the most important factor determining PRA levels 2
- Sensitization level, which can be measured by %PRA 4
- Presence of DSAs, which can increase the risk of antibody-mediated rejection (AMR) 3
Clinical Relevance of Antibodies
The clinical relevance of antibodies in cadaveric donors is significant, as they can: