Organ donor shortage has made transplantation across incompatible* people increasingly popular in recent times. Availability of better methods of detecting and characterizing anti-HLA antibodies **, ease of diagnosis, better understanding of antibody-related rejection, and the availability of effective treatments has made this possible. Desensitization is one such promising arena. This can be done in patients who are incompatible with their potential donor because of blood type or tissue sensitivity.***
Antibodies are proteins that are produced by white blood cells to help the body fight infection. Antibodies circulate in the blood and bind to foreign proteins to stop them from causing damage to the body. The production of antibodies is the body's first line of defense in the immune response. These antibodies work hard to protect our bodies and keep us healthy. However, these same antibodies are bad for someone receiving an organ transplant because the body can also form antibodies against foreign tissues, such as those found on a donated kidney. If a transplant is performed on someone who has these antibodies to their donor kidney, then the kidney will be rejected immediately.
Desensitization is a process that removes harmful antibodies from the blood stream. These antibodies, which fight foreign tissues like those found on a donated organ, can cause organ rejection. People who have this type of antibody typically develop them through a previous exposure to foreign tissue, such as a prior transplant, blood transfusion, or pregnancy. The antibody removal process is called plasmapheresis.
Plasmapheresis treatments involve a plasma exchange that removes harmful antibodies from the blood. After each treatment, the drug immunoglobulin is given to help prevent the harmful antibodies from coming back. The number of treatments a patient needs is determined by the level of harmful antibodies present in his or her blood. These levels are checked frequently to determine if additional treatments are needed. Typically, two to four treatments are required prior to transplant. At the start of the plasmapheresis treatments, the patient receives anti-rejection medications to help prevent the reformation of the harmful antibodies. These anti-rejection medications are the same medications that the patient will continue to use after transplantation.
In organ donation, the most important test is the cross-match test. This test compares the blood cells of the donor and recipient. A laser identifies the presence and intensity of any antibodies the recipient might have against the donor. If the test is negative, antibodies that would work against the donated organ are not present, and the transplant can safely proceed. A positive result shows that antibodies that would work against the donor are present, meaning the organ would be rejected immediately.
About 30 percent of patients who are awaiting an organ transplant are considered “sensitized.” A test called Panel Reactive Antibody (PRA) is used to estimate the amount of anti-HLA antibodies against foreign human tissue in each patient. The PRA tells us the likelihood of having an anti-HLA antibody against a particular donor. A patient is considered sensitized if their PRA is greater than 20 percent. This means they react or have anti-HLA antibodies to 20 percent of the most common HLA antigens. The level of sensitization increases as the PRA percentage increases. Having anti-HLA antibodies against foreign tissues (antigens) makes it harder to find a compatible living or deceased donor kidney. Sensitized patients may wait 3 to 4 times longer for a compatible deceased donor kidney than a non-sensitized patient would.
At this stage, there are three options if the patient and donor have a positive cross-match. They include waiting for another donor who has a negative cross-match, participating in a donor exchange program, or undergoing the desensitization process.
The desensitization process begins with medications targeted to reduce the amount of anti-HLA antibodies in the patient's blood. These medications are aimed at the blood cells that produce the antibodies. Next, the plasmapheresis (a process in which the liquid in the blood, or plasma, is separated from the cells. In sick people, plasma can contain antibodies that attack the immune system. A machine removes the affected plasma and replaces it with good plasma, or a plasma substitute) treatments are started. These treatments involve a plasma exchange that removes harmful anti-HLA antibodies from the blood. After each treatment, the drug immune globulin (IVIg) is given to help prevent the harmful antibodies from coming back. The number of treatments a patient needs is determined by the level of anti-HLA antibodies present in their blood. These levels are checked frequently to determine if additional treatments are needed. Typically, 3 to 5 treatments are required before transplant. At the start of the plasmapheresis treatments, the patient receives anti-rejection medications to help prevent production of new anti-HLA antibodies. These anti-rejection medications are the same medications that the patient will continue to use after transplantation. Plasmapheresis treatments may be necessary following transplantation to reduce the risk of rejection. The number of treatments will depend on antibody levels. The majority of patients receive 3 to 6 treatments.
A desensitized patient can receive organs from any donor without facing the risk of rejection.
* Donors and corresponding recipients of organs must have compatible blood type for the success of organ acceptance.
In living donation, the following blood types are compatible:
- Donors with blood type A... can donate to recipients with blood types A and AB
- Donors with blood type B... can donate to recipients with blood types B and AB
- Donors with blood type AB... can donate to recipients with blood type AB only
- Donors with blood type O... can donate to recipients with blood types A, B, AB and O (O is the universal donor: donors with O blood are compatible with any other blood type)
- Recipients with blood type O... can receive a kidney from blood type O only
- Recipients with blood type A... can receive a kidney from blood types A and O
- Recipients with blood type B... can receive a kidney from blood types B and O
- Recipients with blood type AB... can receive a kidney from blood types A, B, AB and O (AB is the universal recipient: recipients with AB blood are compatible with any other blood type)
** The human leukocyte antigen (HLA) system is a gene complex encoding the major histocompatibility complex (MHC) proteins in humans. These cell-surface proteins are responsible for regulation of the immune system in humans.
*** The susceptibility of individual tissues to injury. The injury may be by way of inflammation, necrosis or cessation of cell growth. Fast-growing tissues in which the cells have a high mitotic index are the most sensitive, especially gonads, germinative layer of skin and erythropoietic tissues. Therefore tissue typing is important. Identification of tissue types for purposes of predicting acceptance or rejection of grafts and organ trans-plants. The process and purposes of tissue typing are essentially the same as for blood typing.
The major difference lies in the kinds of antigens being evaluated. White blood cells, particularly lymp-hocytes, are used for tissue typing. The acceptance of organs depends particularly on the matching of MHC antigens. If the donor and recipient are not MHC identical, the organ is rejected.