Rejection Prophylaxis

Rejection General Information

The main barrier that is encountered in the medical field of surgical transplants is the Rejection of the transplanted tissues and / or organs. This is a common occurrence in the case of transplants, as the immune system is expected to recognize and destroy any foreign presences within the organism, be it bacteria and viruses or tissues and organs. It occurs as a reaction from the recipient organism to specific antigens that are present in the donor tissue, most commonly as a result of cell-mediated and humoral response from the recipient organism. Once the organism detects the presence of these antigens, Rejection is initiated. This is a process that occurs in two stages; the first stage (known under the name of “sensitization”) is characterized by the response of lymphocytes to the presence of the foreign antigen molecules which leads to rapid proliferation of the white cells. The second stage of the process (known as the “effector” stage), the recipient organism destroys the graft through a complex of molecular and cellular mechanisms. The process can be either chronic, acute or hyperacute, and the categorization is made based on the speed of the process. A fourth type is also possible, in cases where xenotransplantion is performed - the hyperacute vascular type.

Rejection Prophylaxis

In this part of our presentation (or second chapter), we intend to present you some detailed information regarding Rejection Prophylaxis. In other words, we will familiarize you with the most common medical techniques that are employed by clinical specialists from all over the world in order to minimize the individual’s risk of experiencing such a transplant-related medical complication.

Studies have shown that certain cells that are naturally found in the human organism (they are called the T cells) play a very important part in the specific immune responses of our organisms. In other words, they may be the ones responsible for most transplant-related complications of this kind. For this reason, most scientists consider T cells the key of any effective prophylactic measure for unwanted transplant-linked complications.

Due to today’s progress in medicine, there are various ways in which a well trained health care provider can diminish the patient’s risks of experiencing such an unwanted complication after a transplant surgery. Most Rejection Prophylaxis routines are known to be based on the beneficial effects of various immuno-suppressive medical products. Other drugs that may be employed for the same purpose (apart from certain immuno-suppressive remedies) include the intake of high doses of corticosteroid medications and polyclonal and / or monoclonal antibodies – these medical products may also be prescribed in the therapy against this unpleasant (and potentially severe) transplant-related complication.

Some health care providers consider the triple-drug treatment trial (that involves the intake of corticosteroid remedies, Cyclosporin, and Azathioprine) as one of the most effective Rejection Prophylaxis medical options, especially in the case of kidney transplants. However, the continuous quest for more effective medical products that should serve the same purpose promises new results (new prophylactic measures) in the foreseeable future. Some clinical substances that offer patients from all over the world great hope include: Tacrolimus, Mizoribine, Mycophenolate mofetil, Sirolimus, and so on.
 
Although the use of the OKT3 anti-T cell monoclonal antibodys used to be commonly prescribed in the Rejection Prophylaxis routines that were implemented in hospitals from all over the world (and it was also employed in the therapy against such conditions), it has now fallen out of the list of advised prophylactic remedies due to its severe adverse reactions (among which: post-transplant lymphoproliferative disease, cytokine release syndrome, and so on).

Rejection Treatment

While chronic Rejection cannot be effectively treated and is irreversible, with the only possible solution being re-transplantation (however this may only be performed ten years after the initial transplant has been attempted), the acute form of the process can be treated by using immunosuppressive drugs. Initially, the treatment involves high-dose corticosteroid administration for a short period of time. This therapy is sufficient to ensure the success of the treatment. However in some cases it may be insufficient, situations in which the health care professionals may opt either for repeating the procedure or for employing a triple therapy regimen which consists of a combination between corticosteroids, anti-proliferative agents and calcineurin inhibitors. In patients that may not tolerate steroids or calcineurin inhibitors, mTOR inhibitors can be used. Blood transfusions may be employed as well in order to remove the antibodies that may attack the graft.

Where it is possible, a bone marrow transplant may provide a solution to the Rejection. The bone marrow transplant must be the same person that has donated the organ or tissue, a clone or an identical twin, and in this case the recipient’s immune system is replaced by the donor’s and thus the tissue / organ is no longer recognized as foreign. Bone marrow transplants are never rejected– this is the only type of transplant that is known to have this property. However, there is a risk that the bone marrow transplant may recognize the recipient tissues as foreign, and proceed to attack and destroy them.