From Wikipedia, the free encyclopedia Transplant rejection
Transplant rejection
Transplant rejection significant in liver allografts and cellular transplants be-
cause these tissues have remarkable regenerative abili-
Classification and external resources ties. Hyperacute rejection is the outcome of xenotrans-
planted organ in non-immunosuppressed recipients.
Acute rejection
Main article: Histocompatibility
Acute rejection may begin as early as 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
Micrograph showing lung transplant rejection. Lung transplantation. A single episode of acute rejection is not
biopsy. H&E stain. a cause for concern if recognized and treated promptly,
ICD-10
ICD- T86. and rarely leads to organ failure. But recurrent episodes
are associated with chronic rejection (see below).
MedlinePlus 000815
Acute rejection occurs to some degree in all trans-
MeSH D006084 plants (except those between identical twins) unless the
immune response is altered through the use of immuno-
Transplant rejection occurs when a transplanted organ suppressive drugs. It is caused by mismatched HLA,
or tissue is not accepted by the body of the transplant re- which are present on all cells of the body. There are a
cipient. This is explained by the concept that the immune large number of different alleles of each HLA, so a perfect
system of the recipient attacks the transplanted organ or match between all HLA in the donor tissue and the recip-
tissue. This is expected to happen, because the immune ient’s body is extremely rare.
system’s purpose is to distinguish foreign material within Tissues such as the kidney or the liver which are
the body and attempt to destroy it, just as it attempts to highly vascularized (rich in blood vessels), are often the
destroy infecting organisms such as bacteria and virus- earliest victims of acute rejection. In fact, episodes of
es. When possible, transplant rejection can be reduced acute rejection occur in around 10-30% of all kidney
through serotyping to determine the most appropriate transplants, and 50 to 60% of liver transplants. Damage to
donor-recipient match and through the use of immuno- the endothelial lining of blood vessels is an early predic-
suppressant drugs.[1] tor of irreversible acute transplant rejection.
The reason that acute rejection usually begins one
Types of rejection week after transplantation is the delay in activation of
the involved T-cells. Often transplanted organs are ac-
quired from a cadaveric source (e.g. trauma victim) and
Hyperacute rejection as a result of ischemia and/or trauma are already in a
Hyperacute rejection is a complement-mediated re- state of inflammation. The inflammatory response re-
sponse in recipients with pre-existing antibodies to the sults in donor-derived dendritic cells migrating to the
donor (for example, ABO blood type antibodies). Hypera- secondary lymphoid tissues (e.g. lymph node) of the re-
cute rejection occurs within minutes after the transplant cipient. There they present self-antigen derived from the
and must be immediately removed to prevent a severe donated organ to recipient T-cells. T-cells that interact
systemic inflammatory response. Rapid agglutination of with allogeneic HLA complexes have the potential to be-
the blood occurs. This is a particular risk in kidney trans- come activated and develop an immune response against
plants, and so a prospective cytotoxic crossmatch is per- the 1.) self-peptide, 2.) the allogeneic HLA molecule itself,
formed prior to kidney transplantation to ensure that or 3.) a combination of both. These T-cells must differen-
antibodies to the donor are not present. Hyperacute re- tiate before the alloreaction begins and the tissue is re-
jection is analogous to a blood transfusion reaction as it jected. The alloreactive T-cells cause cells in the trans-
is a humoral-mediated immune response. For other or- planted tissue to lyse, or produce cytokines that cause
gans, hyperacute rejection is prevented by transplanting necrosis of the transplanted tissue. This process can take
only ABO-compatible grafts. Hyperacute rejection is not days, or even weeks to manifest.
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From Wikipedia, the free encyclopedia Transplant rejection
Organ/tissue Mechanism
Blood Antibodies (isohaemagglutinins)
Kidney Antibodies, CMI
Heart Antibodies, CMI
Skin CMI
Bonemarrow CMI
Cornea Usually accepted unless vascularised, CMI
The first successful organ transplant, performed in Clinically, patients present with progressive airflow ob-
1954 by Dr. Joseph Murray, was successful because the struction often associated with dyspnea and coughing.
donor and recipient were identical twins, and therefore Ultimately these patients succumb to pulmonary insuf-
no T-cell-mediated responses could be generated against ficiency or secondary infection. Bronchiolitis obliterans
the transplanted organ. syndrome (BOS) is used to describe patients with airflow
The diagnosis of acute rejection relies on clinical da- obstruction that cannot be ascribed to any other specific
ta, including patient signs and symptoms, laboratory cause. This diagnosis is confirmed by a persistent drop
testing and ultimately a tissue biopsy. The biopsy is inter- (three or more weeks) in forced expiratory volume
preted by a pathologist who notes changes in the tissue (FEV1) of at least 20%.[5] Unfortunately, BOS is common
that suggest rejection. Generally the pathologist looks in patients after lung transplant and presents in at least
for three main histological features. First, the presence 50% of patients by 5 years and over 80% by ten years post-
of T-cells infiltrating the transplanted tissue; these may transplant.
be accompanied by a heterogeneous collection of other The progression of disease is unpredictable and het-
cell types including eosinophils, plasma cells and neu- erogeneous. In some cases, patients may develop a sud-
trophils. (The proportions of these cell types may be den drop in lung function which then stabilizes for years.
helpful in diagnosing the exact type of rejection.) Se- In other instances, the progression is rapid leading to
condly, evidence of structural injury to the transplanted death within a few months. Although the onset of chron-
tissue; the characteristics of this injury will depend on ic lung rejection is unknown, risk factors include prior
the type of tissue being transplanted. Lastly, injury to the acute cellular rejection episodes, gastroesophageal reflux
blood vessels in the transplanted tissue. disease, infection (viral and bacterial), age of transplant
Recent technological advancements have led to ge- recipient, HLA mis-matching, lymphocytic bronchiolitis
netic expression testing in the form of a blood test. These and graft dysfunction (e.g. airway ischemia).[6]
tests, such as AlloMap Molecular Expression Testing have Rejection is a recipient response to a foreign antigen
a high negative predictive value help manage the ACR re- with the antigen being the transplanted organ or allo-
jection in transplant patients. These genetic expression graft. Histologically, lymphocytic infiltrates are first not-
tests are specific to the transplanted organ type. ed and this is followed by epithelial cell injury (at least
within the lungs). The associated inflammatory reaction
Chronic rejection results in recruitment and proliferation of fibroblasts
The term "chronic rejection" was initially a term used to and myofibroblasts which leads to airway lesions and
describe a long-term loss of function in transplanted or- scarring.[7] The condition is often patchy and heteroge-
gans, associated with fibrosis of the internal blood ves- neous and thus a bronchial biopsy in early disease may
sels of the transplanted tissue. But this pathology is now miss the formation of the granulation tissue that ulti-
termed chronic allograft vasculopathy. The term chronic mately can lead to obliteration of airways.
rejection is reserved for cases of transplant rejection
where the rejection is due to a poorly understood chronic Rejection mechanisms
inflammatory and immune response against the trans-
planted tissue. Rejection is an adaptive immune response and is medi-
ated through both T cell mediated and humoral immune
Chronic rejection of the lungs (antibodies) mechanisms. The number of mismatched al-
Chronic rejection after lung transplantation is the lead- leles determines the speed and magnitude of the rejec-
ing cause of long-term morbidity in lung transplant pa- tion response. Different mechanisms tend to act against
tients.[2][3] The median survival of lung-transplant pa- different grafts.
tients is approximately 4.7 years—about half that of oth- CMI=Cell mediated immunity
er major transplanted organ recipients.[4] Histopatholog-
ically, the condition is known as bronchiolitis obliterans.
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From Wikipedia, the free encyclopedia Transplant rejection
Treatment of rejection • Rituximab
The monoclonal anti-T cell antibody OKT3 was formerly
Chronic transplant rejection is irreversible and cannot be used in the prevention of rejection, and is occasionally
treated effectively. Treatments with inhaled ciclosporin used in treatment of severe acute rejection, but has fallen
are being investigated as a means to delay or prevent out of common use due to the severe cytokine release
chronic rejection of the lungs. At present the only defini- syndrome and late post-transplant lymphoproliferative
tive treatment is re-transplantation, if patients can be re- disorder, which are both commonly associated with use
allocated and if donors are available. of OKT3; in the United Kingdom it is available on a
Acute transplant rejection can be treated using named-patient use basis only.
chemotherapeutic drugs designed to suppress the im- Current diagnosis of organ rejection following trans-
mune system (see list below). Acute rejection is normally plantation relies on tissue biopsy, which is not ideal due
treated initially with a short course of high-dose cor- to sampling limitations and risks associated with the in-
ticosteroids, which is usually sufficient. If this is not vasive procedure. Cellular MRI of in vivo labeled immune
enough, the course can be repeated or a triple therapy reg- cells offers a noninvasive approach to detect and monitor
imen can be used, consisting of a corticosteroid plus a graft rejection after solid organ transplantation. Clinical
calcineurin inhibitor and an anti-proliferative agent. An- application of a reliable and noninvasive technique to de-
tibodies against specific components of the immune sys- tect the early signs of graft rejection will improve not on-
tem can be added to this regimen, especially for high- ly the therapeutic treatment of transplant patients but
risk patients. mTOR inhibitors can be used in selected pa- also improve their quality of life. (Magnetic Resonance in
tients, where calcineurin inhibitors or steroids are con- Medicine (2011)
traindicated. Acute rejection refractory to these treat-
ments may require blood transfusions to remove anti-
bodies against the transplant.
References
If a bone marrow transplant can be performed, the • Gorman, Rachael Moeller. "The Transplant Trick,"
transplant recipient’s immune system can be replaced Proto, Spring 2009.
with the donor’s immune system, thus enabling the re- [1] Christoph Frohn, Lutz Fricke, Jan-Christoph
cipient’s body to accept the new organ without risk of re- Puchta, and Holger Kirchner. The effect of HLA-C
jection. This requires that the bone marrow, which pro- matching on acute renal transplant rejection.
duces the immune cells, be from the same person as the Nephrol. Dial. Transplant. 16: 355-360.
organ donation (or an identical twin or a clone). There is http://ndt.oxfordjournals.org/cgi/content/full/
a risk of graft versus host disease (GVHD) in which the 16/2/355
lymphoid cells co-injected with the bone marrow trans- [2] Pediatr Transplant. 2005 Feb;9(1):84-93
plant recognize the host tissues as foreign and attack and [3] Eur Respir J Suppl. 2003 Nov;47:57s-64s
destroy them accordingly. [4] www.optn.org
[5] Am J Respir Crit Care Med. 2007 Jun
Immunosuppressive drugs used to treat 1;175(11):1192-8
transplant rejection [6] Proc Am Thorac Soc. 2009 6(1):108-21
[7] Proc Am Thorac Soc. 2006 3: 444-49
• • Ciclosporin
• Tacrolimus
• • Sirolimus External links
• Everolimus • The Immune Tolerance Network
• • Azathioprine
• Mycophenolic acid
• • Prednisolone
• Hydrocortisone
• • Monoclonal anti-IL-2Rα receptor antibodies
• Basiliximab
• Daclizumab
• Polyclonal anti-T-cell antibodies
• Anti-thymocyte globulin (ATG)
• Anti-lymphocyte globulin (ALG)
• Monoclonal anti-CD20 antibodies
Retrieved from "http://en.wikipedia.org/wiki/Transplant_rejection"
Categories: Immune system disorders, Transplantation medicine
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From Wikipedia, the free encyclopedia Transplant rejection
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