Donor-specific antibody

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Donor-specific antibodies (DSA) are a concept in transplantation medicine and describe the presence of antibodies specific to the Donor's HLA-Molecules. These antibodies can cause antibody-mediated rejection and are therefore considered a contraindication against transplantation in most cases. [1] DSA are a result of B cell and plasma cell activation and bind to HLA and/or non-HLA molecules on the endothelium [1] of the graft. They were first described in 1969 by Patel et al., who found that Transplant recipients who were positively tested for DSA using a complement-dependent cytotoxicity crossmatch assay had a higher risk of transplant rejection. [2] [3] DSA can either be pre-formed (e.g. by pregnancy, prior transplantation or blood transfusion) or can be formed as a response to the transplantion. [ citation needed ](De novo DSA)

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Almost a third of patients who are waitlisted for transplantation may have a degree of pre-formed DSA. Pre-formed antibodies increase the chances of immunological failure of the allograft by causing positive crossmatches and, thereby, result in the exclusion of donors. [4] For patients with pre-formed DSA, successful transplantation can still be possible by employing strategies such as desensitisation, paired exchange and acceptable mismatching. [5] [6]

Panel reactive antibody

The degree of cytotoxicity is expressed as percentage PRA (panel reactive antibody). It is a tool that can be employed to approximate the risk of a given recipient of having a positive crossmatch. This is to a likely organ donor taken from a similar population. The limitations of this method are that PRA percent can be different numerically without a corresponding change in the type or amount of antibody. This largely depends on the cell panel used which are commercially produced and may not truly represent the population. HLA frequencies and racial differences need to be factored in but cannot be done. Moreover, significant false positive results can be produced due to non-HLA antibodies, autoantibodies and nonspecific IgM antibodies. Similarly, false negative results are possible as this is purely complement dependent that requires higher antibody titres to be activated. [7] [8] The lack of a complement activation simply due to low titres allows a true antibody to be hidden. [9]

Cross-match test

Patel and Terasaki [2] in 1969 demonstrated the efficacy of complement-dependent lymphocytotoxic cross-match in defining immunologic risk in renal transplantation. This became the standard method, still used today, for graft allocation. With PRA that identifies several antibodies to a potential cluster of donors, the crossmatch will identify if a recipient had antibodies to a specific donor of interest. It became clear with time that it did not identify all preexisting donor-specific HLA antibodies (HLA-DSA). In recent years, techniques for detection of HLA antibodies have become more sensitive with the introduction of solid-phase assays, including ELISA. [10]

Related Research Articles

Histocompatibility, or tissue compatibility, is the property of having the same, or sufficiently similar, alleles of a set of genes called human leukocyte antigens (HLA), or major histocompatibility complex (MHC). Each individual expresses many unique HLA proteins on the surface of their cells, which signal to the immune system whether a cell is part of the self or an invading organism. T cells recognize foreign HLA molecules and trigger an immune response to destroy the foreign cells. Histocompatibility testing is most relevant for topics related to whole organ, tissue, or stem cell transplants, where the similarity or difference between the donor's HLA alleles and the recipient's triggers the immune system to reject the transplant. The wide variety of potential HLA alleles lead to unique combinations in individuals and make matching difficult.

<span class="mw-page-title-main">Organ transplantation</span> Medical procedure in which an organ is removed from one body and placed in the body of a recipient

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.

<span class="mw-page-title-main">Liver transplantation</span> Type of organ transplantation

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.

<span class="mw-page-title-main">Transplant rejection</span> Rejection of transplanted tissue by the recipients immune system

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.

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.

<span class="mw-page-title-main">Xenotransplantation</span> Transplantation of cells or tissue across species

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.

<span class="mw-page-title-main">Kidney transplantation</span> Medical procedure

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.

<span class="mw-page-title-main">Cross-matching</span> Testing before a blood transfusion

Cross-matching or crossmatching is a test performed before a blood transfusion as part of blood compatibility testing. Normally, this involves adding the recipient's blood plasma to a sample of the donor's red blood cells. If the blood is incompatible, the antibodies in the recipient's plasma will bind to antigens on the donor red blood cells. This antibody-antigen reaction can be detected through visible clumping or destruction of the red blood cells, or by reaction with anti-human globulin. Along with blood typing of the donor and recipient and screening for unexpected blood group antibodies, cross-matching is one of a series of steps in pre-transfusion testing. In some circumstances, an electronic cross-match can be performed by comparing records of the recipient's ABO and Rh blood type against that of the donor sample. In emergencies, blood may be issued before cross-matching is complete. Cross-matching is also used to determine compatibility between a donor and recipient in organ transplantation.

<span class="mw-page-title-main">BK virus</span> Member of the polyomavirus family

The BK virus is a member of the polyomavirus family. Past infection with the BK virus is widespread, but significant consequences of infection are uncommon, with the exception of the immunocompromised and the immunosuppressed. BK virus is an abbreviation of the name of the first patient, from whom the virus was isolated in 1971.

Tissue typing is a procedure in which the tissues of a prospective donor and recipient are tested for compatibility prior to transplantation. Mismatched donor and recipient tissues can lead to rejection of the tissues. There are multiple methods of tissue typing.

A panel-reactive antibody (PRA) is a group of antibodies in a test serum that are reactive against any of several known specific antigens in a panel of test leukocytes or purified HLA antigens from cells. It is an immunologic metric routinely performed by clinical laboratories on the blood of people awaiting organ transplantation.

<span class="mw-page-title-main">Paul Terasaki</span>

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.

Human leukocyte antigens (HLA) began as a list of antigens identified as a result of transplant rejection. The antigens were initially identified by categorizing and performing massive statistical analyses on interactions between blood types. This process is based upon the principle of serotypes. HLA are not typical antigens, like those found on surface of infectious agents. HLAs are alloantigens, they vary from individual to individual as a result of genetic differences. An organ called the thymus is responsible for ensuring that any T-cells that attack self proteins are not allowed to live. In essence, every individual's immune system is tuned to the specific set of HLA and self proteins produced by that individual; where this goes awry is when tissues are transferred to another person. Since individuals almost always have different "banks" of HLAs, the immune system of the recipient recognizes the transplanted tissue as non-self and destroys the foreign tissue, leading to transplant rejection. It was through the realization of this that HLAs were discovered.

Bernd Schröppel, M.D., is a former transplant nephrologist at the Mount Sinai Medical Center and the former Medical Director of the Kidney Pancreas Transplant Program at the Recanati/Miller Transplantation Institute at the Mount Sinai Medical Center in New York City. He is also a former Assistant Professor of Nephrology at the Mount Sinai School of Medicine.

<span class="mw-page-title-main">Intestine transplantation</span> Surgical replacement of the small intestine

Intestine transplantation is the surgical replacement of the small intestine for chronic and acute cases of intestinal failure. While intestinal failure can oftentimes be treated with alternative therapies such as parenteral nutrition (PN), complications such as PN-associated liver disease and short bowel syndrome may make transplantation the only viable option. One of the rarest type of organ transplantation performed, intestine transplantation is becoming increasingly prevalent as a therapeutic option due to improvements in immunosuppressive regimens, surgical technique, PN, and the clinical management of pre and post-transplant patients.

Complement-dependent cytotoxicity (CDC) is an effector function of IgG and IgM antibodies. When they are bound to surface antigen on target cell, the classical complement pathway is triggered by bonding protein C1q to these antibodies, resulting in formation of a membrane attack complex (MAC) and target cell lysis.

Kidney paired donation (KPD), or paired exchange, is an approach to living donor kidney transplantation where patients with incompatible donors swap kidneys to receive a compatible kidney. KPD is used in situations where a potential donor is incompatible. Because better donor HLA and age matching are correlated with lower lifetime mortality and longer lasting kidney transplants, many compatible pairs are also participating in swaps to find better matched kidneys. In the United States, the National Kidney Registry organizes the majority of U.S. KPD transplants, including the largest swaps. The first large swap was a 60 participant chain in 2012 that appeared on the front page of the New York Times and the second, even larger swap, included 70 participants and was completed in 2014. Other KPD programs in the U.S. include the UNOS program, which was launched in 2010 and completed its 100th KPD transplant in 2014, and the Alliance for Paired Donation.

<span class="mw-page-title-main">Jim Dempster</span> British surgeon

William James Dempster was a British surgeon and researcher in organ transplantation at St Mary’s Hospital, London. He published more than 100 scientific reviews and papers on kidney transplant rejection in dogs, confirming that rejection was an example of immune response, mediated by serum antibodies.

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

  1. 1 2 Lionaki S, Panagiotellis K, Iniotaki A, Boletis JN. Incidence and clinical significance of de novo donor specific antibodies after kidney transplantation. Clin Dev Immunol. 2013; 2013:849835.
  2. 1 2 Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969; 280(14):735-9.
  3. ↑ Stiller CR, Sinclair NR, Abrahams S, Ulan RA, Fung M, Wallace AC. Lymphocyte-dependent antibody and renal graft rejection.. Lancet. 1975; 1(7913):953-4.
  4. ↑ Tinckam KJ. Basic histocompatibility testing methods. In:Chandraker A, editor. Core concepts in renal transplantation. New York:Springer Science + Business Media, LLC; 2012.21–42.
  5. ↑ Stegall MD, Gloor J, Winters JL, Moore SB, Degoey S. A comparison of plasmapheresis versus high-dose IVIG desensitization in renal allograft recipients with high levels of donor specific alloantibody. Am J Transplant. 2006;6(2):346-51.
  6. ↑ Gentry SE, Segev DL, Simmerling M, Montgomery RA. Expanding kidney paired donation through participation by compatible pairs. Am J Transplant. 2007; 7(10):2361-70.
  7. ↑ Amos DB, Cohen I, Klein WJ Jr. Mechanisms of immunologic enhancement. Transplant Proc. 1970; 2(1):68-75.
  8. ↑ Kerman RH, Kimball PM, Van Buren CT, Lewis RM, DeVera V, Baghdahsarian V, Heydari A, Kahan BD. AHG and DTE/AHG procedure identification of crossmatch-appropriate donor-recipient pairings that result in improved graft survival. Transplantation. 1991; 51(2):316-20.
  9. ↑ Gebel HM, Bray RA. Sensitization and sensitivity: defining the unsensitized patient. Transplantation. 2000; 69(7):1370-4.
  10. ↑ Gebel HM, Bray RA, Nickerson P. Pre-transplant assessment of donor-reactive, HLA-specific antibodies in renal transplantation: contraindication vs. risk. Am J Transplant. 2003; 3(12):1488-500.
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