Rejection reaction and immunosuppressors
Summary/Definition
Organ transplantation and immune response
Organ transplantation is a procedure aimed at restoring the function of an organ in a patient suffering from an incurable disease in which the organ is damaged and is no longer able to perform its functions, and also cannot be treated with existing methods. This is achieved by transplanting a donor organ. However, after surgery, the patient’s immune system begins to attack and reject the transplanted organ, which leads to a complication known as the “rejection reaction”. Currently, the use of powerful immunosuppressors can reduce the frequency of symptoms or signs of rejection reactions. Sometimes this reaction manifests itself only in a change in the indicators of functional tests of the organ, even in the absence of obvious symptoms. For successful organ transplantation, it is necessary to overcome the rejection reaction. It can be prevented or treated with immunosuppressive agents that suppress the patient’s immune system so that it does not attack the transplanted organ.
What is a rejection reaction?
The transplant rejection reaction is an immunological response in which the recipient’s immune system perceives the transplanted organ as a foreign object and begins to attack it. There are several types of rejection reactions, including hyperacute, acute and chronic rejection reactions. An ultra-acute rejection reaction occurs when the recipient’s antibodies begin to attack the transplanted organ due to the presence of previously formed antibodies in the recipient’s body directed against the donor’s antigens. In an acute rejection reaction, the recipient’s immune cells recognize the antigens of the transplanted organ and begin to attack them. An acute rejection reaction may occur shortly after transplantation. The chronic rejection reaction develops gradually and leads to the slow destruction of the transplanted organ. The causes can be both immunological (for example, repeated acute rejection reaction) and non-immunological (for example, ischemic lesion, hypertension, hyperglycemia and hyperlipidemia). The rejection reaction is associated with an immune response to histocompatibility antigens and blood group antigens. Histocompatibility antigens, for example, Human leukocyte antigen (HLA), are located on the 6th human chromosome. The greater the overlap between the HLA antigens in the donor and recipient, the less likely an acute rejection reaction is. Blood group antigens (for example, ABO antigens) located on the surface of red blood cells can also cause a rejection reaction, since they are present in the vascular cells of the transplanted organ and can cause the same rejection as with blood transfusion.
Symptoms
Symptoms of organ transplant rejection reactions may include fever, jaundice, abdominal pain, ascites, decreased urination, edema, and blood pressure regulation disorders during kidney transplantation. However, now, when strong immunosuppressants are used, in most cases the symptoms of a rejection reaction do not appear. In the event of a rejection reaction, it is possible to detect violations in functional tests of organs. For example, during liver transplantation, the indicators of a functional liver test may be abnormal, and during kidney transplantation, the level of creatinine in the blood may be increased.
Diagnostics
Examination before organ transplantation
Before organ transplantation, a number of examinations must be performed, including a histocompatibility antigen (HLA) test and a blood group antigen (ABO) test. The histocompatibility antigen test helps to prevent rejection reactions and related complications by analyzing the correspondence of histocompatibility antigens between the recipient and the donor. The blood group antigen test reduces the risk of an acute rejection reaction that may occur after transplantation by analyzing blood group antigens and antibodies in the blood of the recipient and donor. These measures help to reduce the likelihood of a serious rejection reaction and related complications.
Diagnosis of rejection reaction
The rejection reaction can be suspected on the basis of clinical or laboratory signs, and it is confirmed by biopsy of the transplanted organ. The rejection reaction that develops after organ transplantation proceeds slowly due to the immune response, and its immediate detection may be difficult due to the current use of powerful immunosuppressors. Therefore, regular monitoring is necessary. Clinical manifestations of rejection reactions include spontaneous pain or soreness at the site of organ transplantation, decreased urination volume, increased body weight, increased blood pressure and serum creatinine levels. Examinations include blood tests, urine and biopsy, the results of which diagnose the rejection reaction. Diagnostics also includes determining the type of rejection reaction and the degree of tissue damage to the transplanted organ based on the results of a biopsy, identifying the type of attacking immune cells and the degree of their infiltration.
Treatment and course of the disease
Immunosuppressive therapy
- The importance of immunosuppressive therapy
The most important aspect when taking immunosuppressants is careful adherence to the recommendations for taking medications. Immunosuppressors are medications used to protect transplanted organs by suppressing the immune system to prevent the immune system from attacking the transplanted organ. A graft rejection reaction can occur at any time, so patients need to take immunosuppressants regularly throughout their lives and undergo regular examinations. - Induction and supportive immunosuppressive therapy for the prevention of rejection reactions.
Induction immunosuppressive therapy is a treatment method used to suppress the rejection reaction during hospitalization immediately after transplantation. It involves the administration of injections of basiliximab (Simulect) or thymoglobulin (ATG), which are polyclonal anti-lymphocytic antibodies. Supportive immunosuppressive therapy is a treatment method that is used throughout life after transplantation. In this case, 2-4 immunosuppressants are used simultaneously, which must be taken for the rest of life after transplantation. Both methods contribute to the prevention of rejection reactions. - Immunosuppressive therapy against rejection reaction to treat rejection reaction.
Immunosuppressive therapy to combat the rejection reaction involves the introduction of additional immunosuppressors to restore the patient’s condition after the rejection reaction. This may be required if the rejection reaction occurred despite the use of supportive immunosuppressive therapy or due to improper medication intake.
Treatment of rejection reaction
In the case of an acute rejection reaction, treatment is extremely difficult, therefore it is preferable to prevent it by testing for cross-reactivity of antigens between the donor and recipient. Acute rejection can be treated with intensive therapy, including the use of high doses of steroids, polyclonal anti-lymphocytic antibodies, as well as by correcting supportive immunosuppression, the use of plasmapheresis, rituximab, bortezomib and high-dose injections of immunoglobulin. Treatment of a chronic rejection reaction may include the use of immunosuppressants, treatment of hypertension, hyperlipidemia, hyperglycemia, drug toxicity control, etc.
Immunosuppressors are divided into two types: induction immunosuppressors, for example, antithymocytic globulin, ATG and basiliximab, as well as supportive immunosuppressants, including steroids and calcineurin inhibitors.
< Table: Description of immunosuppressors >
| Drug for induced immunosuppression |
| ATG, antithymocytic globulin |
| Basilximab |
| Supportive immunosuppressive drugs |
| Steroids (prednisone, deflazacort) |
| Calcineurin inhibitors (tacrolimus, cyclosporine A) |
| Mycophenolic acid |
| mTOR inhibitors (sirolimus, everolimus) |
| Mizoribin |
| Azathioprine |
The principle of treatment with immunosuppressants is to maintain the optimal dose, which allows the patient to maintain maximum effectiveness while minimizing side effects. It is important to take into account that even with the same dosage of immunosuppressants in different patients, the concentration of these drugs in the blood may vary due to the individual characteristics of their metabolism. Even at the same concentrations in the blood, patients may have different sensitivity to the immunosuppressive effect and possible side effects. Therefore, it is recommended to periodically monitor the concentration of the drug in the blood of each patient and evaluate his sensitivity to immunosuppressants individually. Treatment with immunosuppressors often involves the use of combination therapy using 2-3 different immunosuppressors acting simultaneously through different mechanisms.
After organ transplantation, it is necessary to take immunosuppressants regularly and visit the hospital to measure the level of drugs in the blood and correct the dosage. Immunosuppressants can reduce the body’s immune defenses, so if symptoms of infection appear, it is important to consult a doctor immediately. It is also important to prevent side effects of immunosuppressants, including monitoring of risk factors such as cancer, blood pressure, blood sugar, hyperlipidemia and osteoporosis.
Non-drug treatment of rejection reaction involves changing and controlling lifestyle in order to reduce the risk of complications. This includes controlling high blood pressure, hyperlipidemia, hyperglycemia, and obesity through proper nutrition, physical activity, and leading a proper lifestyle.
