Transplant rejection
Encyclopedia
Transplant rejection occurs when transplanted
tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.
, involved identical twins, and so no rejection was observed. Otherwise, the number of mismatched gene variants, namely alleles, encoding cell surface molecules called major histocompatibility complex
(MHC), classes I and II, correlate with the rapidity and severity of transplant rejection. In humans MHC is also called human leukocyte antigen
(HLA).
Though cytotoxic-crossmatch assay can predict rejection mediated by cellular immunity, genetic-expression tests specific to the organ type to be transplanted, for instance AlloMap Molecular Expression Testing
, have a high negative predictive value. Transplanting only ABO-compatible grafts, matching blood groups between donor and recipient, helps prevent rejection mediated by humoral immunity
.
(mediated by activated B cells secreting antibody
molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). Different types of transplanted tissues tend to favor different balances of rejection mechanisms.
molecules, developed through an earlier primary exposure that primed adaptive immunity—which matured before the transplant occurring as secondary exposure—the specific antibody crossreacts with donor tissue, as typical after earlier mismatching among A/B/O blood types. Components of innate immunity, then, namely soluble immune proteins called complement
and innate immune cells called phagocytes, inflame and destroy the transplanted tissue.
An antibody molecule, secreted by an activated B cell, then called plasma cell
, is a soluble immunoglobulin (Ig) whose constituent unit is configured alike the letter Y: the two arms are the Fab regions and the single stalk is the Fc region. Each Fab tip is the paratope
, which ligates (binds) a cognate (matching) molecular sequence as well as its 3D shape (its conformation), altogether called epitope
, within a specific antigen.
When the paratope of Ig class gamma (IgG) ligates its epitope, IgG's Fc region conformationally shifts and can host a complement protein, initiating the complement cascade that terminates by punching a hole in a cell membrane, and with many holes so punched, the cell ruptures as fluid rushes in. Molecular motifs of necrotic cell debris are recognized as damage-associated molecular patterns (DAMPs), then, when ligating Toll-like receptors (TLRs) on membranes of innate immune cells, which phagocytes are thereby activated to secrete proinflammatory cytokines recruiting more phagogytes to traffic to the area by sensing the concentration gradient of the secreted cytokines (chemotaxis
). IgG's Fc region also enables opsonization by a phagocyte
—such as neutrophils in blood and macrophages in tissues—which attains improved uptake of cell debris and tissue by seizing the IgG molecule's Fc stalk.
or inflammation
. Dendritic cells (DCs) of the donor tissue migrate to the recipient's peripheral lymphoid tissue—lymphoid follicles and lymph nodes—and present the donor's self peptides to the recipient's naive helper T cells. Primed toward these allogeneic HLA peptides, the helper T cells effect immunomemory at either 1) the donor's self peptides, 2) the allogeneic HLA molecules, or 3) both.
The primed helper T cells establish alloreactive killer T cells whose CD8
receptors dock to the transplanted tissue's MHC class I molecules presenting self peptides, whereupon the T cell receptors
(TCRs) of the killer T cells recognize their epitope
—self peptide now coupled within MHC class I molecules—and transduce signals into the target cell prompting its programmed cell death
by apoptosis
.
When the CD4
receptors of helper T cells dock to their hosts, MHC class II molecules, expressed by select cells, their own TCRs—the paratope—might recognize their matching epitope being presented, and thereupon approximate the secretion of cytokines that had prevailed during their priming event, an aggressively proinflammatory balance of cytokines.
, hyperacute rejection manifests within minutes after transplant, and if tissue is left implanted brins systemic inflammatory response syndrome
. Of high risk in kidney
transplants is rapid clumping, namely agglutination
, of red blood cells (RBCs or erythrocytes), as an antibody molecule binds multiple target cells at once.
tissues such as kidney or liver often host the earliest signs—particularly at endothelial cells
lining blood vessels—though it eventually occurs in roughly 10 to 30% of kidney transplants, and 50 to 60% of liver transplants. A single episode of acute rejection can be recognized and promptly treated, usually preventing organ failure, but recurrent episodes lead to chronic rejection.
of the transplanted tissue's blood vessels. This is now chronic allograft vasculopathy, however, leaving chronic rejection referring to rejection due to more patent aspects of immunity.
Chronic rejection explains long-term morbidity in most lung-transplant recipients, the median survival roughly 4.7 years, about half the span versus other major organ transplants. In histopathology the condition is bronchiolitis obliterans, which clinically presents as progressive airflow obstruction, often involving dyspnea
and coughing, and the patient eventually succumbs to pulmonary insufficiency or secondary acute infection.
Airflow obstruction not ascribable to other cause is labeled bronchiolitis obliterans syndrome (BOS), confirmed by a persistent drop—three or more weeks—in forced expiratory volume (FEV1) by at least 20%. BOS is seen in over 50% of lung-transplant recipients by 5 years, and in over 80% by ten years. First noted is infiltration by lymphocytes, followed by epithelial cell
injury, then inflammatory lesions and recruitment of fibroblasts and myofibroblasts, which proliferate and secrete proteins forming scar tissue. Generally thought unpredictable, BOS progression varies widely: lung function may suddenly fall but stabilize for years, or rapidly progress to death within a few months. Risk factors include prior acute rejection episodes, gastroesophageal reflux disease, acute infections, particular age groups, HLA mis-matching, lymphocytic bronchiolitis, and graft dysfunction (e.g., airway ischemia).
. The laboratory pathologist generally seeks three main histological
signs: (1) infiltrating T cells, perhaps accompanied by infiltrating eosinophils, plasma cells, and neutrophils, particularly in telltale ratios, (2) structural compromise of tissue anatomy, varying by tissue type transplanted, and (3) injury to blood vessels. Tissue biopsy is restricted, however, by sampling limitations and risks complications of the invasive procedure. Cellular magnetic resonance imaging
(MRI) of immune cells radiolabeled in vivo might offer noninvasive testing.
is being investigated to delay or prevent chronic rejection of lung transplants. Acute rejection is treated with one or multiple of a few strategies.
Immunosuppressive drugs:
, once used to prevent rejection, and still occasionally used to treat severe acute rejection, has fallen into disfavor, as it commonly brings severe cytokine release syndrome
and late post-transplant lymphoproliferative disorder
. (OKT3 is available in the United Kingdom
for named-patient use only.)
Antibody drugs:
can replace the transplant recipient's immune system with the donor's, and the recipient accepts the new organ without rejection. The marrow — reservoir of replenishing blood cells — must be of the individual who donated the organ (or an identical twin or a clone
). There is a risk of graft versus host disease (GVHD), however, whereby mature lymphocytes entering with marrow recognize the new host tissues as foreign and destroy them.
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
tissue is rejected by the recipient's immune system, which destroys the transplanted tissue. Transplant rejection can be lessened by determining the molecular similitude between donor and recipient and by use of immunosuppressant drugs after transplant.
Pretransplant rejection prevention
The first successful organ transplant, performed in 1954 by Joseph MurrayJoseph Murray
Joseph Edward Murray is a retired American plastic surgeon. He performed the first successful human kidney transplant on identical twins on December 23, 1954....
, involved identical twins, and so no rejection was observed. Otherwise, the number of mismatched gene variants, namely alleles, encoding cell surface molecules called major histocompatibility complex
Major histocompatibility complex
Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
(MHC), classes I and II, correlate with the rapidity and severity of transplant rejection. In humans MHC is also called human leukocyte antigen
Human leukocyte antigen
The human leukocyte antigen system is the name of the major histocompatibility complex in humans. The super locus contains a large number of genes related to immune system function in humans. This group of genes resides on chromosome 6, and encodes cell-surface antigen-presenting proteins and...
(HLA).
Though cytotoxic-crossmatch assay can predict rejection mediated by cellular immunity, genetic-expression tests specific to the organ type to be transplanted, for instance AlloMap Molecular Expression Testing
AlloMap Molecular Expression Testing
AlloMap molecular expression testing, developed and commercialized by XDx, is a gene expression profiling test to identify heart transplant recipients with a low probability of one type of transplant rejection. The test is performed on a blood sample, providing a non-invasive test to help manage...
, have a high negative predictive value. Transplanting only ABO-compatible grafts, matching blood groups between donor and recipient, helps prevent rejection mediated by humoral immunity
Humoral immunity
The Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
.
Immunologic rejection mechanisms
Rejection is an adaptive immune response via cellular immunity (mediated by killer T cells inducing apoptosis of target cells) as well as humoral immunityHumoral immunity
The Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
(mediated by activated B cells secreting antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
molecules), though the action is joined by components of innate immune response (phagocytes and soluble immune proteins). Different types of transplanted tissues tend to favor different balances of rejection mechanisms.
Humoral immunity
A recipient's preexisting adaptive antibodyAntibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...
molecules, developed through an earlier primary exposure that primed adaptive immunity—which matured before the transplant occurring as secondary exposure—the specific antibody crossreacts with donor tissue, as typical after earlier mismatching among A/B/O blood types. Components of innate immunity, then, namely soluble immune proteins called complement
Complement system
The complement system helps or “complements” the ability of antibodies and phagocytic cells to clear pathogens from an organism. It is part of the immune system called the innate immune system that is not adaptable and does not change over the course of an individual's lifetime...
and innate immune cells called phagocytes, inflame and destroy the transplanted tissue.
An antibody molecule, secreted by an activated B cell, then called plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
, is a soluble immunoglobulin (Ig) whose constituent unit is configured alike the letter Y: the two arms are the Fab regions and the single stalk is the Fc region. Each Fab tip is the paratope
Paratope
The paratope is the part of an antibody which recognises an antigen, the antigen-binding site of an antibody. It is a small region of the antibody's Fv region and contains parts of the antibody's heavy and light chains....
, which ligates (binds) a cognate (matching) molecular sequence as well as its 3D shape (its conformation), altogether called epitope
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
, within a specific antigen.
When the paratope of Ig class gamma (IgG) ligates its epitope, IgG's Fc region conformationally shifts and can host a complement protein, initiating the complement cascade that terminates by punching a hole in a cell membrane, and with many holes so punched, the cell ruptures as fluid rushes in. Molecular motifs of necrotic cell debris are recognized as damage-associated molecular patterns (DAMPs), then, when ligating Toll-like receptors (TLRs) on membranes of innate immune cells, which phagocytes are thereby activated to secrete proinflammatory cytokines recruiting more phagogytes to traffic to the area by sensing the concentration gradient of the secreted cytokines (chemotaxis
Chemotaxis
Chemotaxis is the phenomenon in which somatic cells, bacteria, and other single-cell or multicellular organisms direct their movements according to certain chemicals in their environment. This is important for bacteria to find food by swimming towards the highest concentration of food molecules,...
). IgG's Fc region also enables opsonization by a phagocyte
Phagocyte
Phagocytes are the white blood cells that protect the body by ingesting harmful foreign particles, bacteria, and dead or dying cells. Their name comes from the Greek phagein, "to eat" or "devour", and "-cyte", the suffix in biology denoting "cell", from the Greek kutos, "hollow vessel". They are...
—such as neutrophils in blood and macrophages in tissues—which attains improved uptake of cell debris and tissue by seizing the IgG molecule's Fc stalk.
Cellular immunity
Transplanted organs are often acquired from a cadaver—usually a host who had succumbed to trauma—and the tissues had already sustained ischemiaIschemia
In medicine, ischemia is a restriction in blood supply, generally due to factors in the blood vessels, with resultant damage or dysfunction of tissue. It may also be spelled ischaemia or ischæmia...
or inflammation
Inflammation
Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...
. Dendritic cells (DCs) of the donor tissue migrate to the recipient's peripheral lymphoid tissue—lymphoid follicles and lymph nodes—and present the donor's self peptides to the recipient's naive helper T cells. Primed toward these allogeneic HLA peptides, the helper T cells effect immunomemory at either 1) the donor's self peptides, 2) the allogeneic HLA molecules, or 3) both.
The primed helper T cells establish alloreactive killer T cells whose CD8
CD8
CD8 is a transmembrane glycoprotein that serves as a co-receptor for the T cell receptor . Like the TCR, CD8 binds to a major histocompatibility complex molecule, but is specific for the class I MHC protein. There are two isoforms of the protein, alpha and beta, each encoded by a different gene...
receptors dock to the transplanted tissue's MHC class I molecules presenting self peptides, whereupon the T cell receptors
T cell receptor
The T cell receptor or TCR is a molecule found on the surface of T lymphocytes that is responsible for recognizing antigens bound to major histocompatibility complex molecules...
(TCRs) of the killer T cells recognize their epitope
Epitope
An epitope, also known as antigenic determinant, is the part of an antigen that is recognized by the immune system, specifically by antibodies, B cells, or T cells. The part of an antibody that recognizes the epitope is called a paratope...
—self peptide now coupled within MHC class I molecules—and transduce signals into the target cell prompting its programmed cell death
Programmed cell death
Programmed cell-death is death of a cell in any form, mediated by an intracellular program. PCD is carried out in a regulated process which generally confers advantage during an organism's life-cycle...
by apoptosis
Apoptosis
Apoptosis is the process of programmed cell death that may occur in multicellular organisms. Biochemical events lead to characteristic cell changes and death. These changes include blebbing, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation...
.
When the CD4
CD4
CD4 is a glycoprotein expressed on the surface of T helper cells, monocytes, macrophages, and dendritic cells. It was discovered in the late 1970s and was originally known as leu-3 and T4 before being named CD4 in 1984...
receptors of helper T cells dock to their hosts, MHC class II molecules, expressed by select cells, their own TCRs—the paratope—might recognize their matching epitope being presented, and thereupon approximate the secretion of cytokines that had prevailed during their priming event, an aggressively proinflammatory balance of cytokines.
| Tissue | Mechanism |
|---|---|
| Blood | Antibodies (isohaemagglutinins) |
| Kidney | Antibodies, cell-mediated immunity (CMI) |
| Heart | Antibodies, CMI |
| Skin | CMI |
| Bonemarrow | CMI |
| Cornea | Usually accepted unless vascularised: CMI |
Hyperacute rejection
Initiated by preexisting humoral immunityHumoral immunity
The Humoral Immune Response is the aspect of immunity that is mediated by secreted antibodies produced in the cells of the B lymphocyte lineage . B Cells transform into plasma cells which secrete antibodies...
, hyperacute rejection manifests within minutes after transplant, and if tissue is left implanted brins systemic inflammatory response syndrome
Systemic inflammatory response syndrome
Systemic inflammatory response syndrome is an inflammatory state affecting the whole body, frequently a response of the immune system to infection, but not necessarily so...
. Of high risk in kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
transplants is rapid clumping, namely agglutination
Agglutination (biology)
Agglutination is the clumping of particles. The word agglutination comes from the Latin agglutinare, meaning "to glue."This occurs in biology in three main examples:...
, of red blood cells (RBCs or erythrocytes), as an antibody molecule binds multiple target cells at once.
Acute rejection
Developing with formation of cellular immunity, acute rejection occurs to some degree in all transplants, except between identical twins, unless immunosuppression is achieved (usually through drugs). Acute rejection begins as early as one week after transplant, the risk highest in the first three months, though it can occur months to years later. Highly vascularVascular
Vascular in zoology and medicine means "related to blood vessels", which are part of the circulatory system. An organ or tissue that is vascularized is heavily endowed with blood vessels and thus richly supplied with blood....
tissues such as kidney or liver often host the earliest signs—particularly at endothelial cells
Endothelium
The endothelium is the thin layer of cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. These cells are called endothelial cells. Endothelial cells line the entire circulatory system, from the heart...
lining blood vessels—though it eventually occurs in roughly 10 to 30% of kidney transplants, and 50 to 60% of liver transplants. A single episode of acute rejection can be recognized and promptly treated, usually preventing organ failure, but recurrent episodes lead to chronic rejection.
Chronic rejection
The term chronic rejection initially described long-term loss of function in transplanted organs via fibrosisFibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
of the transplanted tissue's blood vessels. This is now chronic allograft vasculopathy, however, leaving chronic rejection referring to rejection due to more patent aspects of immunity.
Chronic rejection explains long-term morbidity in most lung-transplant recipients, the median survival roughly 4.7 years, about half the span versus other major organ transplants. In histopathology the condition is bronchiolitis obliterans, which clinically presents as progressive airflow obstruction, often involving dyspnea
Dyspnea
Dyspnea , shortness of breath , or air hunger, is the subjective symptom of breathlessness.It is a normal symptom of heavy exertion but becomes pathological if it occurs in unexpected situations...
and coughing, and the patient eventually succumbs to pulmonary insufficiency or secondary acute infection.
Airflow obstruction not ascribable to other cause is labeled bronchiolitis obliterans syndrome (BOS), confirmed by a persistent drop—three or more weeks—in forced expiratory volume (FEV1) by at least 20%. BOS is seen in over 50% of lung-transplant recipients by 5 years, and in over 80% by ten years. First noted is infiltration by lymphocytes, followed by epithelial cell
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
injury, then inflammatory lesions and recruitment of fibroblasts and myofibroblasts, which proliferate and secrete proteins forming scar tissue. Generally thought unpredictable, BOS progression varies widely: lung function may suddenly fall but stabilize for years, or rapidly progress to death within a few months. Risk factors include prior acute rejection episodes, gastroesophageal reflux disease, acute infections, particular age groups, HLA mis-matching, lymphocytic bronchiolitis, and graft dysfunction (e.g., airway ischemia).
Rejection detection
Diagnosis of acute rejection relies on clinical data—patient signs and symptoms—but also calls on laboratory data such as tissue biopsyBiopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
. The laboratory pathologist generally seeks three main histological
Histology
Histology is the study of the microscopic anatomy of cells and tissues of plants and animals. It is performed by examining cells and tissues commonly by sectioning and staining; followed by examination under a light microscope or electron microscope...
signs: (1) infiltrating T cells, perhaps accompanied by infiltrating eosinophils, plasma cells, and neutrophils, particularly in telltale ratios, (2) structural compromise of tissue anatomy, varying by tissue type transplanted, and (3) injury to blood vessels. Tissue biopsy is restricted, however, by sampling limitations and risks complications of the invasive procedure. Cellular magnetic resonance imaging
Magnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) of immune cells radiolabeled in vivo might offer noninvasive testing.
Rejection treatment
Hyperacute rejection minifests severely and within minutes, and so treatment is immediate: removal of the tissue. Chronic rejection is generally considered irreversible and poorly amenable to treatment—only retransplant generally indicated if feasible—though inhaled ciclosporinCiclosporin
Ciclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
is being investigated to delay or prevent chronic rejection of lung transplants. Acute rejection is treated with one or multiple of a few strategies.
Immunosuppressive therapy
A short course of high-dose corticosteroids can be applied, and repeated. Triple therapy adds a calcineurin inhibitor and an anti-proliferative agent. Where calcineurin inhibitors or steroids are contraindicated, mTOR inhibitors are used.Immunosuppressive drugs:
- Corticosteroids
- PrednisolonePrednisolonePrednisolone is the active metabolite of prednisone, which is also used as a drug.-Uses:Prednisolone is a corticosteroid drug with predominant glucocorticoid and low mineralocorticoid activity, making it useful for the treatment of a wide range of inflammatory and auto-immune conditions such as...
- Hydrocortisone
- Prednisolone
- CalcineurinCalcineurinCalcineurin is a protein phosphatase also known as protein phosphatase 3, PPP3CA, and calcium-dependent serine-threonine phosphatase, and formerly known as protein phosphatase 2B . It activates the T cells of the immune system and can be blocked by drugs...
inhibitors- CiclosporinCiclosporinCiclosporin , cyclosporine , cyclosporin , or cyclosporin A is an immunosuppressant drug widely used in post-allogeneic organ transplant to reduce the activity of the immune system, and therefore the risk of organ rejection...
- TacrolimusTacrolimusTacrolimus is an immunosuppressive drug that is mainly used after allogeneic organ transplant to reduce the activity of the patient's immune system and so lower the risk of organ rejection...
- Ciclosporin
- Anti-proliferatives
- AzathioprineAzathioprineAzathioprine is a purine analogue immunosuppressive drug. It is used to prevent organ rejection following organ transplantation and to treat a vast array of autoimmune diseases, including rheumatoid arthritis, pemphigus, inflammatory bowel disease , multiple sclerosis, autoimmune hepatitis, atopic...
- Mycophenolic acidMycophenolic acidMycophenolic acid INN or mycophenolate is an immunosuppressant drug used to prevent rejection in organ transplantation. It inhibits an enzyme needed for the growth of T cells and B cells. It was initially marketed as the prodrug mycophenolate mofetil to improve oral bioavailability. More...
- Azathioprine
- mTOR inhibitors
- SirolimusSirolimusSirolimus , also known as rapamycin, is an immunosuppressant drug used to prevent rejection in organ transplantation; it is especially useful in kidney transplants. A macrolide, sirolimus was first discovered as a product of the bacterium Streptomyces hygroscopicus in a soil sample from Easter...
- EverolimusEverolimusEverolimus is the 40-O- derivative of sirolimus and works similarly to sirolimus as an mTOR inhibitor....
- Sirolimus
Antibody-based treatments
Antibody specific to select immune components can be added to immunosuppressive therapy. The monoclonal anti-T cell antibody OKT3OKT3
Muromonab-CD3 is an immunosuppressant drug given to reduce acute rejection in patients with organ transplants. It is a monoclonal antibody targeted at the CD3 receptor, a membrane protein on the surface of T cells...
, once used to prevent rejection, and still occasionally used to treat severe acute rejection, has fallen into disfavor, as it commonly brings severe cytokine release syndrome
Cytokine release syndrome
Cytokine release syndrome is a common immediate complication occurring with the use of anti-T cell antibody infusions such as ATG, OKT3 and TGN1412. Severe cases are known as cytokine storms....
and late post-transplant lymphoproliferative disorder
Post-transplant lymphoproliferative disorder
Post-transplant lymphoproliferative disorder is the name given to a B-cell proliferation due to therapeutic immunosupression after organ transplantation. These patients may develop infectious mononucleosis-like lesions or polyclonal polymorphic B-cell hyperplasia...
. (OKT3 is available in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
for named-patient use only.)
Antibody drugs:
- Monoclonal anti-IL-2Rα receptor antibodies
- BasiliximabBasiliximabBasiliximab is a chimeric mouse-human monoclonal antibody to the α chain of the IL-2 receptor of T cells. It is used to prevent rejection in organ transplantation, especially in kidney transplants...
- DaclizumabDaclizumabDaclizumab is a therapeutic humanized monoclonal antibody to the alpha subunit of the IL-2 receptor of T cells. It is used to prevent rejection in organ transplantation, especially in kidney transplants....
- Basiliximab
- Polyclonal anti-T-cell antibodies
- Anti-thymocyte globulinAnti-thymocyte globulinAnti-thymocyte globulin is an infusion of horse or rabbit-derived antibodies against human T cells which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia.-Uses:...
(ATG) - Anti-lymphocyte globulinAnti-lymphocyte globulinAnti-lymphocyte globulin is an infusion of horse-derived or more commonly rabbit-derived antibodies against human T cells which is used in the treatment of acute rejection in organ transplantation, especially in kidney transplants. It was developed at the University of Minnesota by Dr...
(ALG)
- Anti-thymocyte globulin
- Monoclonal anti-CD20 antibodies
- RituximabRituximabRituximab, sold under the trade names Rituxan and MabThera, is a chimeric monoclonal antibody against the protein CD20, which is primarily found on the surface of B cells...
- Rituximab
Blood transfer
Cases refractory to immunosuppressive or antibody therapy are sometimes given blood transfusions—removing antibody molecues specific to the transplanted tissue.Marrow transplant
Bone marrow transplantBone marrow transplant
Hematopoietic stem cell transplantation is the transplantation of multipotent hematopoietic stem cell or blood, usually derived from bone marrow, peripheral blood stem cells, or umbilical cord blood...
can replace the transplant recipient's immune system with the donor's, and the recipient accepts the new organ without rejection. The marrow — reservoir of replenishing blood cells — must be of the individual who donated the organ (or an identical twin or a clone
Cloning
Cloning in biology is the process of producing similar populations of genetically identical individuals that occurs in nature when organisms such as bacteria, insects or plants reproduce asexually. Cloning in biotechnology refers to processes used to create copies of DNA fragments , cells , or...
). There is a risk of graft versus host disease (GVHD), however, whereby mature lymphocytes entering with marrow recognize the new host tissues as foreign and destroy them.