Transplant rejection 529578 225023695 2008-07-11T14:45:28Z 128.36.24.95 /* Acute rejection */ {{Refimprove|date=November 2007}} '''Transplant rejection''' occurs when a [[Organ transplant|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 [[Bacterium|bacteria]] and [[virus]]es. ==Types of rejection== ===Hyperacute rejection=== Hyperacute rejection is a [[complement system|complement]]-mediated response in recipients with pre-existing [[antibody|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 syndrome|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 [[xenotransplantation|xenotransplanted]] organs. ===Acute rejection=== {{main|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 [[Human leukocyte antigen|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 [[histology|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. {|class="wikitable" style="text-align:left" !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|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 [[cloning|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 [[organ transplant|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 [[transplant rejection|reject]] the transplanted liver <ref name="sikora">''[http://www.news.com.au/entertainment/story/0,26278,23106284-5007185,00.html Demi-Lee Brennan has changed blood types and immune system]'' Kate Sikora, [[Daily Telegraph]], January 25, 2008</ref> and she therefore does not need [[immunosuppresant]] medication.<ref name="Dunlop">''[http://abc.com.au/news/stories/2008/01/24/2146032.htm Aust doctors hail teen's transplant 'miracle']'' Sean Rubinsztein-Dunlop, [[ABC News (Australia)]], January 24, 2008</ref> 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.<ref name="sikora"/> ==References== {{Reflist}} ==External links== *[http://www.immunetolerance.org The Immune Tolerance Network] {{Organ transplantation}} [[Category:Immune system disorders]] [[Category:Transplantation medicine]] [[bg:Отхвърляне на трансплантант]] [[de:Abstoßungsreaktion]] [[fr:Rejet de greffe]] [[it:Rigetto]] [[nl:Afstoting]] [[ja:拒絶反応]] [[pl:Odrzucanie przeszczepu]] [[pt:Rejeição de transplante]]