Anti-Human Globulin (AHG) Panel Reactive Antibody (PRA)
AHG-PRA is a laboratory test that measures the percentage of the general population's HLA antigens against which a transplant candidate has preformed antibodies, using an anti-human globulin enhanced complement-dependent cytotoxicity method to detect clinically relevant IgG antibodies. 1
Definition and Methodology
AHG-PRA is a specific technique for measuring panel reactive antibodies that:
- Uses anti-human globulin to enhance the sensitivity of the traditional complement-dependent cytotoxicity (CDC) test
- Reports results as a percentage of reactivity against a panel of HLA antigens
- Specifically detects IgG antibodies, which are clinically relevant in transplantation 1
- Serves as an important tool to identify sensitized patients prior to organ transplantation 2
Clinical Significance
The AHG-PRA test has significant implications for transplantation:
- Higher PRA percentages indicate greater sensitization and difficulty finding compatible donors
- PRA levels ≥50% are considered highly sensitized 3
- PRA levels can fluctuate over time, requiring regular monitoring (monthly, bimonthly, or quarterly) 1
- Historical PRA results are important as they reflect immune memory that could trigger rejection even with a negative current crossmatch 1
Comparison with Other PRA Methods
AHG-PRA is one of several methods to detect anti-HLA antibodies:
- NIH-CDC and Amos-modified NIH-CDC: Traditional methods with lower sensitivity
- AHG-CDC: Enhanced sensitivity for detecting clinically relevant IgG antibodies
- Flow cytometry: More sensitive than AHG-CDC for detecting small quantities of alloantibodies
- ELISA-PRA: More predictive of post-transplant acute rejection and graft loss than AHG-PRA 1
- Flow Bead PRA: Can detect IgG antibodies to HLA antigens in sera reported as non-reactive by ELISA 1
Clinical Applications and Recommendations
For transplant candidates:
- The standard practice is to use the historically highest PRA, current PRA, and immediate pre-transplant sera in donor-specific crossmatches 1
- Patients with high PRA levels should avoid blood transfusions to prevent further sensitization 3
- If transfusion is necessary in highly sensitized patients, leukocyte-poor blood should be used 1, 3
- Previously sensitized patients remain at high immunological risk even with substantial decreases in pre-transplant PRA levels 4
Pitfalls and Caveats
Important considerations when interpreting AHG-PRA results:
- AHG-PRA is a membrane-dependent assay and may not distinguish between anti-HLA and non-HLA reactivity without antibody specificity studies 1
- Limiting historical PRA sera to 3-6 months may miss important immune memory from 12-18 months prior 1
- A negative screening PRA doesn't completely rule out the presence of donor-specific antibodies, as demonstrated by cases where single-antigen testing detected antibodies missed by screening PRA 5
- IgM antibodies detected by AHG-PRA are generally not considered clinically relevant for transplantation 1
The development of newer, more sensitive methods like ELISA and Flow Bead PRA has improved the detection of clinically relevant antibodies, providing better prediction of transplant outcomes than the traditional AHG-PRA method 1, 6.