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Systemic scleroderma, or systemic sclerosis, is an autoimmune rheumatic disease characterised by excessive production and accumulation of collagen, called fibrosis, in the skin and internal organs and by injuries to small arteries. There are two major subgroups of systemic sclerosis based on the extent of skin involvement: limited and diffuse. The limited form affects areas below, but not above, the elbows and knees with or without involvement of the face. The diffuse form also affects the skin above the elbows and knees and can also spread to the torso. Visceral organs, including the kidneys, heart, lungs, and gastrointestinal tract can also be affected by the fibrotic process. Prognosis is determined by the form of the disease and the extent of visceral involvement. Patients with limited systemic sclerosis have a better prognosis than those with the diffuse form. Death is most often caused by lung, heart, and kidney involvement. The risk of cancer is increased slightly.
Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be transported from a donor site to another location. Organs and/or tissues that are transplanted within the same person's body are called autografts. Transplants that are recently performed between two subjects of the same species are called allografts. Allografts can either be from a living or cadaveric source.
Liver transplantation or hepatic transplantation is the replacement of a diseased liver with the healthy liver from another person (allograft). Liver transplantation is a treatment option for end-stage liver disease and acute liver failure, although availability of donor organs is a major limitation. The most common technique is orthotopic transplantation, in which the native liver is removed and replaced by the donor organ in the same anatomic position as the original liver. The surgical procedure is complex, requiring careful harvest of the donor organ and meticulous implantation into the recipient. Liver transplantation is highly regulated, and only performed at designated transplant medical centers by highly trained transplant physicians and supporting medical team. The duration of the surgery ranges from 4 to 18 hours depending on outcome. Favorable outcomes require careful screening for eligible recipient, as well as a well-calibrated live or cadaveric donor match.
Xenotransplantation, or heterologous transplant, is the transplantation of living cells, tissues or organs from one species to another. Such cells, tissues or organs are called xenografts or xenotransplants. It is contrasted with allotransplantation, syngeneic transplantation or isotransplantation and autotransplantation. Xenotransplantation is an artificial method of creating an animal-human chimera, that is, a human with a subset of animal cells. In contrast, an individual where each cell contains genetic material from a human and an animal is called a human–animal hybrid.
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.
Alloimmunity is an immune response to nonself antigens from members of the same species, which are called alloantigens or isoantigens. Two major types of alloantigens are blood group antigens and histocompatibility antigens. In alloimmunity, the body creates antibodies against the alloantigens, attacking transfused blood, allotransplanted tissue, and even the fetus in some cases. Alloimmune (isoimmune) response results in graft rejection, which is manifested as deterioration or complete loss of graft function. In contrast, autoimmunity is an immune response to the self's own antigens. Alloimmunization (isoimmunization) is the process of becoming alloimmune, that is, developing the relevant antibodies for the first time.
Cytotoxic T-lymphocyte associated protein 4, (CTLA-4) also known as CD152, is a protein receptor that functions as an immune checkpoint and downregulates immune responses. CTLA-4 is constitutively expressed in regulatory T cells but only upregulated in conventional T cells after activation – a phenomenon which is particularly notable in cancers. It acts as an "off" switch when bound to CD80 or CD86 on the surface of antigen-presenting cells. It is encoded by the gene CTLA4 in humans.
Co-stimulation is a secondary signal which immune cells rely on to activate an immune response in the presence of an antigen-presenting cell. In the case of T cells, two stimuli are required to fully activate their immune response. During the activation of lymphocytes, co-stimulation is often crucial to the development of an effective immune response. Co-stimulation is required in addition to the antigen-specific signal from their antigen receptors.
CD28 is one of the proteins expressed on T cells that provide co-stimulatory signals required for T cell activation and survival. T cell stimulation through CD28 in addition to the T-cell receptor (TCR) can provide a potent signal for the production of various interleukins.
The Kidd antigen system are proteins found in the Kidd's blood group, which act as antigens, i.e., they have the ability to produce antibodies under certain circumstances. The Jk antigen is found on a protein responsible for urea transport in the red blood cells and the kidney. They are important in transfusion medicine. People with two Jk(a) antigens, for instance, may form antibodies against donated blood containing two Jk(b) antigens. This can lead to hemolytic anemia, in which the body destroys the transfused blood, leading to low red blood cell counts. Another disease associated with the Jk antigen is hemolytic disease of the newborn, in which a pregnant woman's body creates antibodies against the blood of her fetus, leading to destruction of the fetal blood cells. Hemolytic disease of the newborn associated with Jk antibodies is typically mild, though fatal cases have been reported.
CD137, a member of the tumor necrosis factor (TNF) receptor family, is a type 1 transmembrane protein, expressed on surfaces of leukocytes and non-immune cells. Its alternative names are tumor necrosis factor receptor superfamily member 9 (TNFRSF9), 4-1BB, and induced by lymphocyte activation (ILA). It is of interest to immunologists as a co-stimulatory immune checkpoint molecule, and as a potential target in cancer immunotherapy.
ICOS ligand is a protein that in humans is encoded by the ICOSLG gene located at chromosome 21. ICOSLG has also been designated as CD275.
Paul Ichiro Terasaki was an American scientist in the field of human organ transplant technology, and professor emeritus of surgery at UCLA School of Medicine.
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.
Thymoglobulin is an anti-human thymocyte immunoglobulin preparation made of purified polyclonal antibodies derived from rabbits. While these antibodies have a variety of specificities, their main mechanism of immunosuppression is through depletion of T cells. Thymoglobulin is currently approved for clinical use in Europe and the United States for renal allograft rejection, prevention of graft-vs.-host disease, and conditions involving bone marrow failure, including aplastic anemia and has additional off-label uses.
Immutep Ltd is a biotechnology company working primarily in the field of cancer immunotherapy using the LAG3 immune control mechanism. The company was originally built on CVac, a therapeutic cancer vaccine. In late 2014 the privately held French immunotherapy company Immutep SA was purchased by Prima Biotech.
GSK2831781 is a monoclonal antibody being developed by GlaxoSmithKline (GSK) for autoimmune diseases. The antibody targets the T cell activation marker LAG-3, which is mainly expressed in inflamed tissues. In GSK's March 2015 Product development pipeline document the antibody is listed under 'Immuno-inflammation' candidates. GSK2831781 entered a Phase I clinical trial in psoriasis early in 2015.
PD-1 inhibitors and PD-L1 inhibitors are a group of checkpoint inhibitor anticancer drugs that block the activity of PD-1 and PDL1 immune checkpoint proteins present on the surface of cells. Immune checkpoint inhibitors are emerging as a front-line treatment for several types of cancer.
Shimon Slavin is an Israeli professor of medicine. Slavin pioneered the use of immunotherapy mediated by allogeneic donor lymphocytes and innovative methods for stem cell transplantation for the cure of hematological malignancies and solid tumors, and using hematopoietic stem cells for induction of transplantation tolerance to bone marrow and donor allografts.
Alexandre Loupy is a French nephrologist, a university professor and hospital practitioner at the Necker Hospital of the Assistance Publique - Hôpitaux de Paris, in the kidney transplant department. He is known for his discoveries on the topic of graft rejection.,, Its approach proposing innovative methodological tools has led to a better understanding but has also led to important changes in the international classification of graft rejection., These discoveries allow to improve the performance of clinical trials and to consider new therapeutic innovations in transplantation.
References
- ↑ Ville, Simon; Poirier, Nicolas; Branchereau, Julien; Charpy, Vianney; Pengam, Sabrina; Nerriere-Daguin, Véronique; Le Bas-Bernardet, Stéphanie; Coulon, Flora; Mary, Caroline; Chenouard, Alexis; Hervouet, Jeremy; Minault, David; Nedellec, Steven; Renaudin, Karine; Vanhove, Bernard; Blancho, Gilles (December 2016). "Anti-CD28 Antibody and Belatacept Exert Differential Effects on Mechanisms of Renal Allograft Rejection". Journal of the American Society of Nephrology. 27 (12): 3577–3588. doi: 10.1681/ASN.2015070774 .
- ↑ Zhang, T.; Gheorghe, B.; Sun, W.; Rybak, E.; Harris, D.; Sievert, E.; Burdorf, L.; Cheng, X.; Vanhove, B.; Azimzadeh, A.; Pierson, R. Iii (15 July 2014). "Effect of FR104, a Novel Anti-CD28 Fab, in Monkey Cardiac Allograft Transplantation.: Abstract# 1490". Transplantation. 98: 33. ISSN 0041-1337.
- ↑ Poirier, N.; Mary, C.; Dilek, N.; Hervouet, J.; Minault, D.; Blancho, G.; Vanhove, B. (October 2012). "Preclinical Efficacy and Immunological Safety of FR104, an Antagonist Anti-CD28 Monovalent Fab′ Antibody". American Journal of Transplantation. 12 (10): 2630–2640. doi: 10.1111/j.1600-6143.2012.04164.x .
- ↑ Poirier, N.; Dilek, N.; Mary, C.; Ville, S.; Coulon, F.; Branchereau, J.; Tillou, X.; Charpy, V.; Pengam, S.; Nerriere-Daguin, V.; Hervouet, J.; Minault, D.; Le Bas-Bernardet, S.; Renaudin, K.; Vanhove, B.; Blancho, G. (February 2015). "FR104, an Antagonist Anti-CD28 Monovalent Fab' Antibody, Prevents Alloimmunization and Allows Calcineurin Inhibitor Minimization in Nonhuman Primate Renal Allograft". American Journal of Transplantation. 15 (1): 88–100. doi: 10.1111/ajt.12964 .
- ↑ Poirier, Nicolas; Blancho, Gilles; Hiance, Maryvonne; Mary, Caroline; Van Assche, Tim; Lempoels, Jos; Ramael, Steven; Wang, Weirong; Thepenier, Virginie; Braudeau, Cecile; Salabert, Nina; Josien, Regis; Anderson, Ian; Gourley, Ian; Soulillou, Jean-Paul; Coquoz, Didier; Vanhove, Bernard (15 December 2016). "First-in-Human Study in Healthy Subjects with FR104, a Pegylated Monoclonal Antibody Fragment Antagonist of CD28". The Journal of Immunology. 197 (12): 4593–4602. doi: 10.4049/jimmunol.1601538 .