Rejection In Organ Transplants And Its Prevention
The immune system fights off and protects the body from harmful pathogens or bacteria. It does this by recognizing antigens that are on the surfaces of the harmful pathogens and bacteria. Transplant rejection is triggered when the immune system attacks the organ or tissue that is being transplanted because it recognizes the antigens present are not from the recipient’s body and indicates them as foreign and attacks them. The three main types of rejection are hyperacute, acute, and chronic rejection. Another important disease that can arise after a transplant is called graft versus host disease, also known as GVHD, due to complications in bone marrow transplants. Due to these organ rejections and diseases, immunosuppression drugs and mechanisms have been developed to help combat and reduce the effects of organ transplant rejections. Another possible technique that has recently came to surface to aid in rejections and disease is xenotransplantation.
The first type of rejection is hyperacute rejection. It is called hyperacute because the rejection acts immediately after the transplant occurs. This quick rejection is caused by the antibodies in the recipient’s immune system that react against antigens on the transplanted organ. The antibodies bind to endothelium and trigger the blood-clotting cascade, leading to an enlarged, ischemic graft and rapid death of the organ over the course of hours. Diagnosis of hyper acute rejection can be signaled by manifestations that generally include malaise and a high fever. Following diagnosis, prevention of hyperacute rejection is uncommon when the recipient is pre-screened for transplant cross-matches. Thus, once hyper acute rejection starts to occur, usually minutes after the transplant, the safest thing to do is to surgically remove the organ or tissue immediately, so the recipient does not die. Hyperacute rejection is usually unresponsive to treatments such as medicine, so the only logical thing to do is remove the rejected organ or tissue and follow with an immediate re-transplantation.
The second type of rejection is called acute rejection. This is the rejection of a tissue or organ graft from a genetically unrelated donor that occurs within 10-13 days of transplantation unless prevented by immunosuppressant treatment. Acute rejection can be characterized by the intrusion of T lymphocytes into the graft area. It can be diagnosed by doing a histological analysis of graft biopsy. This is done by assessment of the inflammation and healing stage around the specific area. It also monitors the presence and distribution of deteriorating products that dissolve in to the surround organ and/or tissues. Prevention of acute rejection can be done by taking immunosuppressant medicines that will help prevent and reduce the risk of acute rejection occurring. Another prevention factor is making sure the recipients doctor is keeping a close eye on them post-transplant. Treatment of acute rejection can be depicted in terms of a kidney transplant. During a kidney transplant in which acute rejection occurs, the recipient will receive pulse steroid therapy for the first rejection episode. This method can be used again for reoccurring rejection episodes. Furthermore, a single episode of acute rejection can be treated. This will prevent organ and or tissue failure. However, recurrence of acute rejection can result in the long-term outcome of chronic rejection, which can then lead to organ failure.
The third type of rejection is called chronic rejection. Chronic rejection is the late failure of a transplanted organ, which can be due to immunological or non-immunological causes. This is caused by the organ slowly losing its function due to the body’s repeated immune responses attacking it over and over again. This type of rejection can develop over many years. Diagnosis of chronic rejection can be described in terms of a lung transplant. Symptoms of chronic rejection in a patient can include things such as sequential shortness of breath and a drop shown in spirometry levels – which are basic exams used to determine how well your lungs work. Additionally, a bronchoscopy, which is a common procedure that lets doctors look into your lungs, is usually performed to diagnose chronic rejection. Prevention of rejection by getting ABO blood typing and histocompatibility antigen testing (HLA) done before hand can help assure the recipient for a more compatible match. Furthermore, since chronic rejection cannot be treated effectively with medicines, it is very likely that it can lead to another organ transplant or result in organ failure.
In addition, graft vs host disease (GVHD) is another name for the allograft rejection reaction. The term is used mainly in relation to bone marrow transplantation when immune cells of the donor are present and recognize and destroy transplanted bone marrow or hematopoietic stem cells (HSCs) in the host’s own tissues. GVHD can be broken down into either acute-GVHD or chronic-GVHD. Symptoms can range from moderate to severe/life-threatening. Common signs include jaundice, skin inflammation and irritation, GI tract discomfort, and many other organ problems. GVHD can be diagnosed through the use of a tissue biopsy when the patient’s symptoms indicate that GVHD is present. Blood tests are another way to diagnose GVHD. However, since there is no certainty that GVHD can be fully-prevented, techniques have become more developed to reduce the risk of developing GVHD. Such techniques include more precision when determining whether donor cells are a good match for the recipient. Another prevention factor is more precise processing of the donor cells to remove T lymphocytes. Moreover, blood from the umbilical cord being used as an origin of donor cells can help reduce the chances of developing the infection. The trademark of treatment for GVHD is immunosuppressant medications. Doctors use corticosteroids as the main treatment therapy for GVHD, but there are also non-steroid medications available for when GVHD does not act in response well with steroid treatments. The outcome of GVHD varies upon how severe the symptoms are, the extent of the symptoms, and how effective the treatments are.
Following rejections and disease, immunosuppression medicines are used to suppress the recipient’s immune system by prohibiting it to attack the newly transplanted organ. There are two types of drugs: induction and maintenance drugs. Induction drugs are given at the time of the transplant and maintenance drugs are used for long term. The four main types of maintenance drugs are calcineurin inhibitors, anti-proliferative agents, mTOR inhibitor, and steroids. All of these drugs are antirejection drugs that are used for the long-term rejection episodes. The dosages of these drugs also vary depending on the severity of the rejection episode. However, these drugs can cause very severe side effects. Some side effects include: weight gain, hair loss, high blood pressure, kidney toxicity, osteoporosis, increased cholesterol levels, etc. Taking these medications can make a person more susceptible to getting an infection and even cancer.
On the other hand, some less-harmful mechanisms that are currently being researched are things such as gene therapy. Gene therapy has the potential to remove problems that are associated with suppression of the immune system by allowing for the donor grafts to produce immunomodulatory proteins, which would result in a local immunosuppression rather than a systemic one. Gene therapy interventions can potentially prevent graft damage owing to nonimmune-mediated graft loss or injury, which can result in preventing chronic rejection. Furthermore, these gene therapy approaches could remove the requirement for general immunosuppression by allowing the induction of donor-specific tolerance.
Lastly, xenotransplantation is the process of grafting or transplanting cells, tissues, and/or organs from one living species to another. Xenotransplantation was developed due to the high demand for human organs in transplantations. I believe that this could be possible in our lifetime. However, I am not certain as to whether or not the recipient of the transplant would want another species inside of them or not because of risk factors such as infection. Alternatively, there are a few pros of xenotransplantation, which include: promising life-saving benefits, having the potential to open up new areas of research, could potentially satisfy the supply and demand of organs, and it reduces the chances of organ donations in the black market. On the other hand, some cons of xenotransplantation include: how it brings about moral issues, it poses the risk of disease transmission, it risks shorter life spans of animal organs, and it has a very high rejection rate. There is still a lot more clinical research to be done on xenotransplantation.
In conclusion, organ rejection is something that impacts the lives of many people who go through the procedure of an organ transplant. Luckily, there are many immunosuppressant drugs that have been discovered to prevent organ rejection from occurring. However, these drugs can cause terrible side effects, so researchers have been working to discover less harmful mechanisms to use to prevent rejection such as gene therapy. Another rising technique is xenotransplantation, which could be a possibility in the near future. These mechanisms help prevent hyperacute, acute, and chronic rejection, and graft vs host disease. Although the immune system is made to protect our body from harmful pathogens, it is actually what detects the organ being transplanted and triggers rejection within the recipient. With our advancing medical field, we are able to continue to discover and research new ways for recipients to accept the organs they need.
References
- Bagley, J., & Iacomini, J. (2003). Gene Therapy Progress and Prospects: Gene therapy in organ transplantation. Gene Therapy, 10(8), 605–611. doi: 10.1038/sj.gt.3302020
- Center for Biologics Evaluation and Research. (n.d.). Xenotransplantation. Retrieved October 10, 2019, from https://www.fda.gov/vaccines-blood-biologics/xenotransplantation.
- Dugdale, D. C. (Ed.). (n.d.). Transplant rejection: MedlinePlus Medical Encyclopedia. Retrieved October 10, 2019, from https://medlineplus.gov/ency/article/000815.htm.
- Harmon, W. E., Thomas, B., Weir, M. R., Gautreaux, M. D., & Van Dyke, K. (n.d.). Hyperacute Graft Rejection. Retrieved October 10, 2019, from https://www.sciencedirect.com/topics/medicine-and-dentistry/hyperacute-graft-rejection.
- Immunosuppressant’s. (2017, February 3). Retrieved October 10, 2019, from https://www.kidney.org/atoz/content/immuno.
- Stöppler, M. C. (2018, February). Graft Versus Host Disease Symptoms, Prognosis & GVHD Treatment. Retrieved October 9, 2019, from https://www.medicinenet.com/graft_versus_host_disease_gvhd/article.htm#graft-versus-host_disease_gvhd_facts.
- UNOS. (n.d.). Preventing Rejection: Side effects. Retrieved October 10, 2019, from https://transplantliving.org/after-the-transplant/preventing-rejection/side-effects/.
