The Panel Reactive Antibody (PRA) is a blood test performed on patients awaiting an organ transplant to determine their degree of immune sensitization. The test assesses whether the recipient’s immune system has developed pre-existing antibodies that could recognize and potentially reject a donated organ. The PRA score is presented as a percentage that estimates the proportion of the general donor population a patient would react against. A higher percentage indicates a highly sensitized patient, meaning they face a greater immunological barrier to successful transplantation.
Understanding HLA and Antibody Sensitization
Immune sensitization in transplantation is based on Human Leukocyte Antigens (HLA), proteins found on the surface of most cells in the body. These antigens act like genetic identification tags, allowing the immune system to distinguish between the body’s own cells and foreign material. When an organ is transplanted, the recipient’s immune system recognizes the donor’s HLA as foreign, triggering an immune response.
Sensitization occurs when a person is exposed to foreign HLA antigens from another individual. Common exposure events include previous blood transfusions, prior organ transplants, or pregnancy, where the mother is exposed to paternal HLA from the fetus. The immune system responds by creating antibodies specifically targeted against those foreign HLA proteins.
How Panel Reactive Antibody Scores Are Determined
The traditional Panel Reactive Antibody test involved mixing the patient’s blood serum with a physical panel of lymphocytes (white blood cells) from a large group of anonymous donors. The resulting percentage reflected how many donors in that physical panel the patient’s antibodies reacted against, providing an estimate of the patient’s likelihood of reacting to a randomly selected organ.
Modern transplantation centers primarily use the Calculated Panel Reactive Antibody (cPRA), which offers a more precise and standardized measurement. The cPRA is an algorithmic calculation based on the specific HLA antibodies identified in the patient’s blood. These antibodies are compared against known HLA frequencies within the national or regional donor population, providing an estimate of the percentage of donors the patient would be incompatible with.
The cPRA score is a more accurate tool because it uses a large, data-driven set of HLA profiles, better representing the true diversity of the donor pool. For instance, a cPRA of 80% signifies that the patient has antibodies against HLA types present in 80% of the potential deceased donor population. This calculated score allows for a clearer assessment of immunologic risk and the probability of a positive crossmatch with a donor.
The Direct Impact of PRA on Transplant Eligibility
The Panel Reactive Antibody score has significant practical consequences for a patient awaiting an organ. A low cPRA score (below 20%) suggests the patient is compatible with a large number of donors, typically leading to shorter waiting times. Conversely, a high cPRA (80% or greater) severely limits the pool of compatible organs, often resulting in years on the waiting list.
A high level of pre-existing antibodies increases the risk of hyperacute rejection, a severe injury that can destroy the donated organ within hours of transplant. To avoid this outcome, transplant teams perform a crossmatch test between the recipient’s blood and the donor’s cells before surgery. A high cPRA means the probability of a positive crossmatch is much higher, which immediately contraindicates the transplant.
The cPRA data is used to perform a “virtual crossmatch,” comparing the recipient’s known unacceptable HLA antigens electronically against the potential donor’s HLA profile. This process allows for rapid screening of incompatible organs, ensuring only donors without the recipient’s target antibodies are considered. Because highly sensitized patients have fewer potential matches, allocation systems often grant them priority points to increase access to compatible organs.
Strategies for Highly Sensitized Patients
For patients with high cPRA scores, strategies focus on two main approaches: reducing the antibody level or expanding the compatible donor pool. Desensitization protocols are treatments designed to temporarily lower the concentration of harmful HLA antibodies in the bloodstream. These protocols often involve procedures such as plasmapheresis, which removes the patient’s plasma containing the antibodies.
Desensitization is frequently combined with medications like high-dose intravenous immunoglobulin (IVIg), which helps neutralize the remaining antibodies. These interventions aim to create a window of opportunity for a safe transplant by reducing the risk of immediate rejection. Another strategy is participation in specialized programs, such as kidney paired donation or exchange programs. These programs facilitate a swap, allowing a highly sensitized patient to receive a compatible kidney while their own incompatible donor gives an organ to another recipient.