Immunosuppression | |
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ICD-10-PCS | D89.9 |
MeSH | D007165 |
Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. [1] [2]
In general, deliberately induced immunosuppression is performed to prevent the body from rejecting an organ transplant. [3] Additionally, it is used for treating graft-versus-host disease after a bone marrow transplant, or for the treatment of auto-immune diseases such as systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, or Crohn's disease. This is typically done using medications, but may involve surgery (splenectomy), plasmapheresis, or radiation. A person who is undergoing immunosuppression, or whose immune system is weak for some other reasons (such as chemotherapy or HIV), is said to be immunocompromised . [4]
Administration of immunosuppressive medications or immunosuppressants is the main method for deliberately inducing immunosuppression; in optimal circumstances, immunosuppressive drugs primarily target hyperactive components of the immune system. [5] People in remission from cancer who require immunosuppression are not more likely to experience a recurrence. [6] Throughout its history, radiation therapy has been used to decrease the strength of the immune system. [7] Dr. Joseph Murray of Brigham and Women's Hospital was given the Nobel Prize in Physiology or Medicine in 1990 for work on immunosuppression. [8]
Immunosuppressive drugs have the potential to cause immunodeficiency, which can increase susceptibility to opportunistic infection and decrease cancer immunosurveillance. [9] Immunosuppressants may be prescribed when a normal immune response is undesirable, such as in autoimmune diseases. [10]
Steroids were the first class of immunosuppressant drugs identified, though side-effects of early compounds limited their use. The more specific[ vague ] azathioprine was identified in 1960, but it was the discovery of ciclosporin in 1980 (together with azathioprine) that allowed significant expansion of transplantation to less well-matched donor-recipient pairs as well as broad application to lung transplantation, pancreas transplantation, and heart transplantation. [3] After an organ transplantation, the body will nearly always reject the new organ(s) due to differences in human leukocyte antigen between the donor and recipient. As a result, the immune system detects the new tissue as "foreign", and attempts to remove it by attacking it with white blood cells, resulting in the death of the donated tissue. Immunosuppressants are administered in order to help prevent rejection; however, the body becomes more vulnerable to infections and malignancy during the course of such treatment. [11] [12] [13]
Non-deliberate immunosuppression can occur in, for example, ataxia–telangiectasia, complement deficiencies, many types of cancer, and certain chronic infections such as human immunodeficiency virus (HIV). The unwanted effect in non-deliberate immunosuppression is immunodeficiency that results in increased susceptibility to pathogens, such as bacteria and viruses. [1]
Immunodeficiency is also a potential adverse effect of many immunosuppressant drugs, in this sense, the scope of the term immunosuppression in general includes both beneficial and potential adverse effects of decreasing the function of the immune system. [14]
B cell deficiency and T cell deficiency are immune impairment that individuals are born with or are acquired, which in turn can lead to immunodeficiency problems. [15] Nezelof syndrome is an example of an immunodeficiency of T-cells. [16]
Progressive multifocal leukoencephalopathy (PML) is a rare and often fatal viral disease characterized by progressive damage (-pathy) or inflammation of the white matter (leuko-) of the brain (-encephalo-) at multiple locations (multifocal). It is caused by the JC virus, which is normally present and kept under control by the immune system. The JC virus is harmless except in cases of weakened immune systems. In general, PML has a mortality rate of 30–50% in the first few months, and those who survive can be left with varying degrees of neurological disabilities.
Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After allogenic organ transplant, the risk of organ rejection is moderate. To lower the risk of organ rejection, tacrolimus is given. The drug can also be sold as a topical medication in the treatment of T-cell-mediated diseases such as eczema and psoriasis. For example, it is prescribed for severe refractory uveitis after a bone marrow transplant, exacerbations of minimal change disease, Kimura's disease, and vitiligo. It can be used to treat dry eye syndrome in cats and dogs.
Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.
A pancreas transplant is an organ transplant that involves implanting a healthy pancreas into a person who usually has diabetes.
Azathioprine, sold under the brand name Imuran, among others, is an immunosuppressive medication. It is used for the treatment of rheumatoid arthritis, granulomatosis with polyangiitis, Crohn's disease, ulcerative colitis, and systemic lupus erythematosus; and in kidney transplants to prevent rejection. It is listed by the International Agency for Research on Cancer as a group 1 human carcinogen. It is taken by mouth or injected into a vein.
Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis, and treat perivascular epithelioid cell tumor (PEComa). It has immunosuppressant functions in humans and is especially useful in preventing the rejection of kidney transplants. It is a mechanistic target of rapamycin kinase (mTOR) inhibitor that inhibits activation of T cells and B cells by reducing their sensitivity to interleukin-2 (IL-2).
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.
Everolimus, sold under the brand name Afinitor among others, is a medication used as an immunosuppressant to prevent rejection of organ transplants and as a targeted therapy in the treatment of renal cell cancer and other tumours.
Mycophenolic acid is an immunosuppressant medication used to prevent rejection following organ transplantation and to treat autoimmune conditions such as Crohn's disease and lupus. Specifically it is used following kidney, heart, and liver transplantation. It can be given by mouth or by injection into a vein. It comes as mycophenolate sodium and mycophenolate mofetil.
Bone marrow suppression also known as myelotoxicity or myelosuppression, is the decrease in production of cells responsible for providing immunity (leukocytes), carrying oxygen (erythrocytes), and/or those responsible for normal blood clotting (thrombocytes). Bone marrow suppression is a serious side effect of chemotherapy and certain drugs affecting the immune system such as azathioprine. The risk is especially high in cytotoxic chemotherapy for leukemia.
Basiliximab, sold under the brand name Simulect, is a monoclonal antibody used to prevent rejection in kidney transplants. It is a chimeric mouse-human monoclonal antibody to the α chain (CD25) of the IL-2 receptor of T cells. It is used in combination with other medicines used to prevent organ rejection.
Anti-thymocyte globulin (ATG) is an infusion of horse or rabbit-derived antibodies against human T cells and their precursors (thymocytes), which is used in the prevention and treatment of acute rejection in organ transplantation and therapy of aplastic anemia due to bone marrow insufficiency.
Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood in order to replicate inside of a patient and to produce additional normal blood cells. It may be autologous, allogeneic or syngeneic.
Immunodeficiency, also known as immunocompromisation, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that affect the patient's immune system. Examples of these extrinsic factors include HIV infection and environmental factors, such as nutrition. Immunocompromisation may also be due to genetic diseases/flaws such as SCID.
Kidney transplant or renal transplant is the organ transplant of a kidney into a patient with end-stage kidney disease (ESRD). Kidney transplant is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ. Living-donor kidney transplants are further characterized as genetically related (living-related) or non-related (living-unrelated) transplants, depending on whether a biological relationship exists between the donor and recipient.
Lung transplantation, or pulmonary transplantation, is a surgical procedure in which one or both lungs are replaced by lungs from a donor. Donor lungs can be retrieved from a living or deceased donor. A living donor can only donate one lung lobe. With some lung diseases, a recipient may only need to receive a single lung. With other lung diseases such as cystic fibrosis, it is imperative that a recipient receive two lungs. While lung transplants carry certain associated risks, they can also extend life expectancy and enhance the quality of life for those with end stage pulmonary disease.
Biological response modifiers (BRMs) are substances that modify immune responses. They can be endogenous or exogenous, and they can either enhance an immune response or suppress it. Some of these substances arouse the body's response to an infection, and others can keep the response from becoming excessive. Thus they serve as immunomodulators in immunotherapy, which can be helpful in treating cancer and in treating autoimmune diseases, such as some kinds of arthritis and dermatitis. Most BRMs are biopharmaceuticals (biologics), including monoclonal antibodies, interleukin 2, interferons, and various types of colony-stimulating factors. "Immunotherapy makes use of BRMs to enhance the activity of the immune system to increase the body's natural defense mechanisms against cancer", whereas BRMs for rheumatoid arthritis aim to reduce inflammation.
Hepatosplenic T-cell lymphoma is a rare form of lymphoma that is generally incurable, except in the case of an allogeneic stem cell transplant. It is a systemic neoplasm comprising medium-sized cytotoxic T-cells that show significant sinusoidal infiltration in the liver, spleen, and bone marrow.
Short Course Immune Induction Therapy or SCIIT, is a therapeutic strategy employing rapid, specific, short term-modulation of the immune system using a therapeutic agent to induce T-cell non-responsiveness, also known as operational tolerance. As an alternative strategy to immunosuppression and antigen-specific tolerance inducing therapies, the primary goal of SCIIT is to re-establish or induce peripheral immune tolerance in the context of autoimmune disease and transplant rejection through the use of biological agents. In recent years, SCIIT has received increasing attention in clinical and research settings as an alternative to immunosuppressive drugs currently used in the clinic, drugs which put the patients at risk of developing infection, cancer, and cardiovascular disease.
Sphingosine-1-phosphate receptor modulators are a class of drugs used as immunomodulators, most notably in cases of multiple sclerosis.
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