Diagnosis:
Transplantation: Alloantibodies
• Alloantibodies are often, but not always, problematic in transplantation.
• Antibody testing methodologies have various advantages and disadvantages and should be used in combination to obtain the most complete picture of a patient’s sensitization status.
• Advantages of complement-dependent cytotoxicity (CDC) methods include the following:
- Detection of the most harmful type of antibodies – namely, the ones that fix complement.
- Detection of IgM and IgG isotypes’ positive reactions in the absence or presence of dithiothreitol (DTT), respectively.
- Differentiation between anti-HLA class I and class II antibodies (positive reactions with T and B cells or B cells only).
- Ability to detect antibodies against non-human leukocyte antigens (HLAs).
- The HLA specificity of antibodies can be resolved in patients who are not broadly presensitized.
• Disadvantages on CDC methods include the following:
- Low sensitivity.
- Possibility of yielding false-positive reactions in patients treated with monoclonal antibody therapies.
• Advantages of solid-phase assay (SPA) testing methods include the following:
- Excellent sensitivity.
- Ability to identify the specificity of anti-HLA antibodies.
- The HLA specificity of antibodies can be resolved by use of single antigen beads.
• Disadvantages of SPA testing methods include the following:
- High sensitivity (i.e., low titer antibodies often do not yield a positive crossmatch and represent little danger to an allograft).
- Inability to detect antibodies against any antigen not represented on the solid phase.
- Inability to differentiate between complement fixing and nonfixing antibodies.
- In most implementations of SPA testing, only IgG is detected.
- Antibody detection may be flawed because the HLA alleles represented on the beads may be different than the one(s) expressed by the donor.
• When gauging the acceptability of alloantibodies in transplantation, the complement fixing ability should be considered; The ability of human IgG subtypes’ to fix complement can be summarized by IgG3 > IgG1 > IgG2 > IgG4 = 0.
• Antibodies that do not fix complement can act as blocking antibodies, masking the target antigens from recognition by T cells, B cells, and other complement fixing antibodies.
