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16-September-2008 16:15:15 - Transplant rejection Redirected from Acute transplant rejection Jump to: navigation, search November 2007 Transplant rejection occurs when a transplanted organ or tissue fails to be accepted by the body of the transplant recipient. This is explained by the concept that the immune system of the recipient attacks the transplanted organ or tissue. This is expected to happen, because the immune system's purpose is to distinguish foreign material within the body and attempt to destroy it, just as it attempts to destroy infecting organisms such as bacteria and viruses. Contents 1 Types of rejection 1.1 Hyperacute rejection 1.2 Acute rejection 1.3 Chronic rejection 2 Rejection mechanisms 3 Treatment of rejection 3.1 Immunosuppressive drugs used to treat transplant rejection 4 Demi-Lee Brennan 5 References 6 External links Types of rejection Hyperacute rejection Hyperacute rejection is a complement-mediated response in recipients with pre-existing antibodies to the donor for example, ABO blood type antibodies. Hyperacute rejection occurs within minutes and the transplant must be immediately removed to prevent a severe systemic inflammatory response. Rapid agglutination of the blood occurs. This is a particular risk in kidney transplants, and so a prospective cytotoxic crossmatch is performed prior to kidney transplantation to ensure that antibodies to the donor are not present. For other organs, hyperacute rejection is prevented by transplanting only ABO-compatible grafts. Hyperacute rejection is the likely outcome of xenotransplanted organs. Acute rejection Main article: Histocompatibility Acute rejection usually begins one week after transplantation as opposed to hyperacute rejection, which is immediate. The risk of acute rejection is highest in the first three months after transplantation. However, acute rejection can also occur months to years after transplantation. A single episode of acute rejection is not a cause for concern if recognised and treated promptly, and rarely leads to organ failure. But recurrent episodes are associated with chronic rejection see below. Acute rejection occurs to some degree in all transplants except those between identical twins. It is caused by mismatched HLA antigens, which are present on all cells of the body. There are a large number of different alleles of each HLA antigen, so a perfect match between all HLA antigens in the donor tissue and the recipient's body is extremely rare. Tissues such as the kidney or the liver which are highly vascularized rich in blood vessels, are often the earliest victims of acute rejection. In fact, episodes of acute rejection occur in around 60-75% of first kidney transplants, and 50 to 60% of liver transplants. Damage to the endothelial lining of blood vessels is an early predictor of irreversible acute transplant rejection. The reason acute rejection usually begins one week after transplantation is that T-cells are involved in the rejection mechanism. These T-cells must differentiate before rejection begins. The T-cells cause cells in the transplanted tissue to lyse, or produce cytokines that cause necrosis of the transplanted tissue. The first successful organ transplant, performed in 1954 by Dr. Joseph Murray, was successful because the donor and recipient were identical twins, and therefore no T-cell-mediated responses could be generated against the transplanted organ. The diagnosis of acute rejection relies on clinical data, including patient signs and symptoms, laboratory testing and ultimately a tissue biopsy. The biopsy is intrepretated by a pathologist who notes changes in the tissue that suggest rejection. Generally the pathologist looks for three main histological features. First, the presence of T-cells infiltrating the transplanted tissue; these may be accompanied by a heterogeneous collection of other cell types including eosinophils, plasma cells and neutrophils. The proportions of these cell types may be helpful in diagnosing the exact type of rejection. Secondly, evidence of structural injury to the transplanted tissue; the characteristics of this injury will depend on the type of tissue being transplanted. Lastly, injury to the blood vessels in the transplanted tissue. Chronic rejection The term chronic rejection was initially a term used to describe a long-term loss of function in transplanted organs, associated with fibrosis of the internal blood vessels of the transplanted tissue. But this pathology is now termed chronic allograft vasculopathy. The term chronic rejection is reserved for cases of transplant rejection where the rejection is due to a chronic immune response against the transplanted tissue. It can be caused by a member of the Minor Histocompatibility Complex such as the H-Y gene of the male Y chromosome. This usually leads to need for a new organ transplant after a decade or so. Rejection mechanisms Rejection is an adaptive immune response and is mediated through both T cell mediated and humoral immune antibodies mechanisms. The number of mismatched alleles determines the speed and magnitude of the rejection response. Different mechanisms tend to act against different grafts. Organ/tissue Mechanism Blood Antibodies isohaemagglutinins Kidney Antibodies, CMI Heart Antibodies, CMI Skin CMI Bonemarrow CMI Cornea Usually accepted unless vascularised, CMI CMI=Cell mediated immunity Treatment of rejection Chronic transplant rejection is irreversible and cannot be treated effectively. The only definitive treatment is re-transplantation, if necessary. This would typically be ten years after a transplant, and this may entail returning to a transplant queue. Acute transplant rejection can be treated using chemotherapeutic drugs designed to suppress the immune system see list below. Acute rejection is normally treated initially with a short course of high-dose corticosteroids, which is usually sufficient to treat successfully. If this is not enough, the course can be repeated or a triple therapy regimen can be used, consisting of a corticosteroid plus a calcineurin inhibitor and an anti-proliferative agent. Antibodies against specific components of the immune system can be added to this regimen, especially for high-risk patients. mTOR inhibitors can be used in selected patients, where calcineurin inhibitors or steroids are contraindicated. Acute rejection refractory to these treatments may require blood transfusions to remove antibodies against the transplant. If a bone marrow transplant can be performed, the transplant recipient's immune system can be replaced with the donor's immune system, thus enabling the recipient's body to accept the new organ without risk of rejection. This requires that the bone marrow, which produces the immune cells, be from the same person as the organ donation or an identical twin or a clone. Bone marrow is not attacked by the body's immune system, and is the only known type of transplant that has this quality. However, there is a risk of graft versus host disease GVHD in which the immune cells arising from the bone marrow transplant recognise the host tissues as foreign and attack and destroy them accordingly. Immunosuppressive drugs used to treat transplant rejection Calcineurin inhibitors Cyclosporin Tacrolimus mTOR inhibitors Sirolimus Everolimus Anti-proliferatives Azathioprine Mycophenolic acid Corticosteroids Prednisolone Hydrocortisone Antibodies Monoclonal anti-IL-2Rα receptor antibodies Basiliximab Daclizumab Polyclonal anti-T-cell antibodies Anti-thymocyte globulin ATG Anti-lymphocyte globulin ALG The monoclonal anti-T cell antibody OKT3 was formerly used in the prevention of rejection, and is occasionally used in treatment of severe acute rejection, but has fallen out of common use due to the severe cytokine release syndrome and late post-transplant lymphoproliferative disorder, which are both commonly associated with use of OKT3; in the United Kingdom it is available on a named-patient use basis only. Demi-Lee Brennan Demi-Lee Brennan is an Australian citizen who after a liver transplant has changed blood type and adopted the immune system of her donor. The upshot of this is that her body no longer attempts to reject the transplanted liver 1 and she therefore does not need immunosuppresant medication.2 Her case is described as unique in that there were no other recorded instances of this ever happening in the history of human organ transplanting. Scientists are now interested in finding out how this happened in hopes of duplicating the process since this may be a solution to the problem of transplant rejection.1 References ^ a b Demi-Lee Brennan has changed blood types and immune system Kate Sikora, Daily Telegraph, January 25, 2008 ^ Aust doctors hail teen's transplant 'miracle' Sean Rubinsztein-Dunlop, ABC News Australia, January 24, 2008 External links The Immune Tolerance Network v d e Organ transplantation Types Allograft · Alloplant · Allotransplantation · Autotransplantation · Xenotransplantation Organs and tissues Bone · Bone marrow · Corneal · Face · Hand · Heart · Heart-lung · Kidney · Liver · Lung · Pancreas · Penis · Skin · Spleen · Uterus Related topics Biomedical tissue · Cellular memory · Edmonton protocol · Eye bank · Graft-versus-host disease · Immunosuppressive drugs · Islet cell transplantation · Implants · Living donor liver transplantation · Lung allocation score · Machine perfusion · Medical grafting · Non-heart beating donation · Organ donation · Post-transplant lymphoproliferative disorder · Repugnant market · Total body irradiation · Transplant rejection Organizations Halachic Organ Donor Society · Human Tissue Authority · National Marrow Donor Program · United Network for Organ Sharing People Christiaan Barnard · Michael Woodruff · Alexis Carrel · Norman Shumway · Jean-Michel Dubernard · List of notable organ transplant donors and recipients v d e Immune disorders: Hypersensitivity and autoimmune diseases I IgE Allergy Food allergy · Atopy Atopic dermatitis · Anaphylaxis · Urticaria · Hay fever II IgM, IgG ADCC · Pernicious anemia · Hemolytic disease of the newborn · Acute transplant rejection · Penicillin allergy autoimmune: Idiopathic thrombocytopenic purpura · Bullous pemphigoid · Autoimmune hemolytic anemia · Goodpasture's syndrome · receptor Graves' disease, Myasthenia gravis · Pemphigus vulgaris · Rheumatic fever III Immune complex Serum sickness · Arthus reaction · Hypersensitivity vasculitis · Reactive arthritis · Henoch-Schönlein purpura · Farmer's lung · Post-streptococcal glomerulonephritis autoimmune: Systemic lupus erythematosus · Subacute bacterial endocarditis IV T-cells Contact dermatitis · Cell-mediated immunity · Mantoux test autoimmune: Temporal arteritis · Diabetes mellitus type 1 · Hashimoto's thyroiditis · Guillain-Barré syndrome · Multiple sclerosis · Rheumatoid arthritis · Coeliac disease Unknown/ multiple Autoimmune hepatitis Retrieved from http://en..org/wiki/Transplant_rejection Categories: Immune system disorders | Transplantation medicineHidden category: Articles needing additional references from November 2007 Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages БългарÑ?ки Deutsch Français Italiano Nederlands Polski Português Suomi This page was last modified on 9 August 2008, at 12:0
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