Panel-reactive antibody

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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. [1]

Traditionally serum is exposed to panel lymphocytes and to an extent other leukocytes in a complement dependent cytotoxicity test. From the extent and pattern of cytotoxicity an estimation of what percentage of the possible donor population the patient has antibodies against is calculated. The PRA score is expressed as a percentage representing the proportion of the population to which the person being tested will react via pre-existing antibodies against human cell surface antigens, which include human leukocyte antigen|HLA] and other polymorphic antigen systems. It is a test of the degree of alloimmunity in a graft recipient and thus a test that quantifies the risk of transplant rejection. Each population has a different demographic prevalence of particular antigens, so the PRA test panel constituents differ from country to country.

Since late 1990's, a purified HLA antigen panel affixed to latex beads coated in fluorochrome, a kind of so called solid phase assay, has been used to replace or complement the cell based assay This test will miss non-HLA antibodies as well as antibodies directed against HLA not included in the assay, but removes the need for panel cells. [2]

A high PRA value usually means that the individual is primed to react immunologically against a large proportion of the population. Individuals with a high PRA value are often termed "sensitized", which indicates that they have been exposed to "foreign" (or "non-self") proteins in the past and have developed antibodies to them. These antibodies typically develop following previous transplants, blood transfusions and pregnancy. Transplanting organs into recipients with pre- formed antibodies may significantly increase the risk of organ rejection. [3]

Extensive efforts have been made to identify treatment regimes to reduce PRA in sensitized transplant candidates. In certain circumstances, plasma exchange, intravenous immunoglobulin, rituximab and other "antibody-directed" immune therapies may be employed, but this is an area in which active investigation continues. [4]

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">Major histocompatibility complex</span> Cell surface proteins, part of the acquired immune system

The major histocompatibility complex (MHC) is a large locus on vertebrate DNA containing a set of closely linked polymorphic genes that code for cell surface proteins essential for the adaptive immune system. These cell surface proteins are called MHC molecules.

<span class="mw-page-title-main">Natural killer cell</span> Type of cytotoxic lymphocyte

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system. They belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cells, stressed cells, tumor cells, and other intracellular pathogens based on signals from several activating and inhibitory receptors. Most immune cells detect the antigen presented on major histocompatibility complex I (MHC-I) on infected cell surfaces, but NK cells can recognize and kill stressed cells in the absence of antibodies and MHC, allowing for a much faster immune reaction. They were named "natural killers" because of the notion that they do not require activation to kill cells that are missing "self" markers of MHC class I. This role is especially important because harmful cells that are missing MHC I markers cannot be detected and destroyed by other immune cells, such as T lymphocyte cells.

<span class="mw-page-title-main">Immunosuppressive drug</span> Drug that inhibits activity of immune system

Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system.

<span class="mw-page-title-main">Lymphocyte</span> Subtype of white blood cell

A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells, B cells, and innate lymphoid cells, of which natural killer cells are an important subtype. They are the main type of cell found in lymph, which prompted the name "lymphocyte". Lymphocytes make up between 18% and 42% of circulating white blood cells.

<span class="mw-page-title-main">Human leukocyte antigen</span> Genes on human chromosome 6

The human leukocyte antigen (HLA) system or complex of genes on chromosome 6 in humans which encode cell-surface proteins responsible for regulation of the immune system. The HLA system is also known as the human version of the major histocompatibility complex (MHC) found in many animals.

<span class="mw-page-title-main">Hypersensitivity</span> Medical condition

Hypersensitivity is an abnormal physiological condition in which there is an undesirable and adverse immune response to antigen. It is an abnormality in the immune system that causes immune diseases including allergies and autoimmunity. It is caused by many types of particles and substances from the external environment or from within the body that are recognized by the immune cells as antigens. The immune reactions are usually referred to as an over-reaction of the immune system and they are often damaging and uncomfortable.

<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.

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">Antibody-dependent cellular cytotoxicity</span> Cell-mediated killing of other cells mediated by antibodies

Antibody-dependent cellular cytotoxicity (ADCC), also referred to as antibody-dependent cell-mediated cytotoxicity, is a mechanism of cell-mediated immune defense whereby an effector cell of the immune system kills a target cell, whose membrane-surface antigens have been bound by specific antibodies. It is one of the mechanisms through which antibodies, as part of the humoral immune response, can act to limit and contain infection.

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.

Macrophage-1 antigen is a complement receptor ("CR3") consisting of CD11b and CD18.

<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.

The following outline is provided as an overview of and topical guide to immunology:

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.

Immune tolerance in pregnancy or maternal immune tolerance is the immune tolerance shown towards the fetus and placenta during pregnancy. This tolerance counters the immune response that would normally result in the rejection of something foreign in the body, as can happen in cases of spontaneous abortion. It is studied within the field of reproductive immunology.

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.

Immunology is the study of the immune system during health and disease. Below is a list of immunology-related articles.

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.

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. DSA are a result of B cell and plasma cell activation and bind to HLA and/or non-HLA molecules on the endothelium 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. DSA can either be pre-formed or can be formed as a response to the transplantion.

References

  1. ↑ Kolonko A, Bzoma B, Giza P, Styrc B, Sobolewski M, Chudek J, Dębska-Ślizień A, Więcek A. The Pre-Transplant Drop in Panel-Reactive Antibodies Titer Evaluated Using Complement-Dependent Cytotoxicity (PRA-CDC) and the Risk of Early Acute Rejection in Sensitized Kidney Transplant Recipients. Medicina (Kaunas). 2018 Sep 20;54(5):66. doi: 10.3390/medicina54050066. PMID 30344297; PMCID: PMC6262586.
  2. ↑ Lachmann N, Todorova K, Schulze H, Schönemann C. Luminex(®) and its applications for solid organ transplantation, hematopoietic stem cell transplantation, & transfusion. Transfus Med Hemother. 2013 Jun;40(3):182-9. doi: 10.1159/000351459. Epub 2013 May 8. PMID 23922543; PMCID: PMC3725018.
  3. ↑ Choi AY, Manook M, Olaso D, Ezekian B, Park J, Freischlag K, Jackson A, Knechtle S, Kwun J. Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization. Front Immunol. 2021 Jun 11;12:694763. doi: 10.3389/fimmu.2021.694763. PMID 34177960; PMCID: PMC8226120.
  4. ↑ Choi AY, Manook M, Olaso D, Ezekian B, Park J, Freischlag K, Jackson A, Knechtle S, Kwun J. Emerging New Approaches in Desensitization: Targeted Therapies for HLA Sensitization. Front Immunol. 2021 Jun 11;12:694763. doi: 10.3389/fimmu.2021.694763. PMID 34177960; PMCID: PMC8226120.
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