Serology

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Serology is the scientific study of serum and other body fluids. In practice, the term usually refers to the diagnostic identification of antibodies in the serum. [1] Such antibodies are typically formed in response to an infection (against a given microorganism), [2] against other foreign proteins (in response, for example, to a mismatched blood transfusion), or to one's own proteins (in instances of autoimmune disease). In either case, the procedure is simple.[ citation needed ]

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Serological tests

Serological tests are diagnostic methods that are used to identify antibodies and antigens in a patient's sample. Serological tests may be performed to diagnose infections and autoimmune illnesses, to check if a person has immunity to certain diseases, and in many other situations, such as determining an individual's blood type. [1] Serological tests may also be used in forensic serology to investigate crime scene evidence. [3] Several methods can be used to detect antibodies and antigens, including ELISA, [4] agglutination, precipitation, complement-fixation, and fluorescent antibodies and more recently chemiluminescence. [5]

Applications

Microbiology

IgG and IgM rapid diagnostic test for COVID-19 IgGIgM-Covid19-Test.jpg
IgG and IgM rapid diagnostic test for COVID-19

In microbiology, serologic tests are used to determine if a person has antibodies against a specific pathogen, or to detect antigens associated with a pathogen in a person's sample. [6] Serologic tests are especially useful for organisms that are difficult to culture by routine laboratory methods, like Treponema pallidum (the causative agent of syphilis), or viruses. [7]

The presence of antibodies against a pathogen in a person's blood indicates that they have been exposed to that pathogen. Most serologic tests measure one of two types of antibodies: immunoglobulin M (IgM) and immunoglobulin G (IgG). IgM is produced in high quantities shortly after a person is exposed to the pathogen, and production declines quickly thereafter. IgG is also produced on the first exposure, but not as quickly as IgM. On subsequent exposures, the antibodies produced are primarily IgG, and they remain in circulation for a prolonged period of time. [6]

This affects the interpretation of serology results: a positive result for IgM suggests that a person is currently or recently infected, while a positive result for IgG and negative result for IgM suggests that the person may have been infected or immunized in the past. Antibody testing for infectious diseases is often done in two phases: during the initial illness (acute phase) and after recovery (convalescent phase). The amount of antibody in each specimen (antibody titer) is compared, and a significantly higher amount of IgG in the convalescent specimen suggests infection as opposed to previous exposure. [8] False negative results for antibody testing can occur in people who are immunosuppressed, as they produce lower amounts of antibodies, and in people who receive antimicrobial drugs early in the course of the infection. [7]

Transfusion medicine

O positive blood type: the patient's red cells are agglutinated by Anti-D (anti-Rh factor) antisera, but not by anti-A and anti-B antisera. The patient's plasma agglutinates type A and B red cells. Blood typing by manual tube method - type O positive.jpg
O positive blood type: the patient's red cells are agglutinated by Anti-D (anti-Rh factor) antisera, but not by anti-A and anti-B antisera. The patient's plasma agglutinates type A and B red cells.

Blood typing is typically performed using serologic methods. The antigens on a person's red blood cells, which determine their blood type, are identified using reagents that contain antibodies, called antisera. When the antibodies bind to red blood cells that express the corresponding antigen, they cause red blood cells to clump together (agglutinate), which can be identified visually. The person's blood group antibodies can also be identified by adding plasma to cells that express the corresponding antigen and observing the agglutination reactions. [9] [6]

Other serologic methods used in transfusion medicine include crossmatching and the direct and indirect antiglobulin tests. Crossmatching is performed before a blood transfusion to ensure that the donor blood is compatible. It involves adding the recipient's plasma to the donor blood cells and observing for agglutination reactions. [9] The direct antiglobulin test is performed to detect if antibodies are bound to red blood cells inside the person's body, which is abnormal and can occur in conditions like autoimmune hemolytic anemia, hemolytic disease of the newborn and transfusion reactions. [10] The indirect antiglobulin test is used to screen for antibodies that could cause transfusion reactions and identify certain blood group antigens. [11]

Interpretation of antibody panel used in serology to detect patient antibodies towards the most relevant human blood group systems. .mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em} Further information: Blood compatibility testing Serology interpretation of antibody panel for blood group antigens.jpg
Interpretation of antibody panel used in serology to detect patient antibodies towards the most relevant human blood group systems.

Immunology

Serologic tests can help to diagnose autoimmune disorders by identifying abnormal antibodies directed against a person's own tissues (autoantibodies). [12] All people have different immunology graphs.[ citation needed ]

Serological surveys

A 2016 research paper by Metcalf et al., amongst whom were Neil Ferguson and Jeremy Farrar, stated that serological surveys are often used by epidemiologists to determine the prevalence of a disease in a population. Such surveys are sometimes performed by random, anonymous sampling from samples taken for other medical tests or to assess the prevalence of antibodies of a specific organism or protective titre of antibodies in a population. Serological surveys are usually used to quantify the proportion of people or animals in a population positive for a specific antibody or the titre or concentrations of an antibody. These surveys are potentially the most direct and informative technique available to infer the dynamics of a population's susceptibility and level of immunity. The authors proposed a World Serology Bank (or serum bank) and foresaw "associated major methodological developments in serological testing, study design, and quantitative analysis, which could drive a step change in our understanding and optimum control of infectious diseases." [13]

In a helpful reply entitled "Opportunities and challenges of a World Serum Bank", de Lusignan and Correa observed [14] that the

principal ethical and logistical challenges that need to be overcome are the methods of obtaining specimens, how informed consent is acquired in busy practices, and the filling in of gaps in patient sampling.

In another helpful reply on the World Serum Bank, the Australian researcher Karen Coates declared that: [15]

Improved serological surveillance would allow governments, aid agencies, and policy writers to direct public health resources to where they are needed most. A better understanding of infection dynamics with respect to the changing patterns of global weather should inform policy measures including where to concentrate vaccination efforts and insect control measures.

In April 2020, Justin Trudeau formed the COVID-19 Immunity Task Force, whose mandate is to carry out a serological survey in a scheme hatched in the midst of the COVID-19 pandemic. [16] [17]

See also

Related Research Articles

<span class="mw-page-title-main">Blood type</span> Classification of blood based on antibodies and antigens on red blood cell surfaces

A blood type is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele and collectively form a blood group system.

Humoral immunity is the aspect of immunity that is mediated by macromolecules – including secreted antibodies, complement proteins, and certain antimicrobial peptides – located in extracellular fluids. Humoral immunity is named so because it involves substances found in the humors, or body fluids. It contrasts with cell-mediated immunity. Humoral immunity is also referred to as antibody-mediated immunity.

<span class="mw-page-title-main">Seroconversion</span> Development of specific antibodies in the blood serum as a result of infection or immunization

In immunology, seroconversion is the development of specific antibodies in the blood serum as a result of infection or immunization, including vaccination. During infection or immunization, antigens enter the blood, and the immune system begins to produce antibodies in response. Before seroconversion, the antigen itself may or may not be detectable, but the antibody is absent. During seroconversion, the antibody is present but not yet detectable. After seroconversion, the antibody is detectable by standard techniques and remains detectable unless the individual seroreverts, in a phenomenon called seroreversion, or loss of antibody detectability, which can occur due to weakening of the immune system or decreasing antibody concentrations over time. Seroconversion refers the production of specific antibodies against specific antigens, meaning that a single infection could cause multiple waves of seroconversion against different antigens. Similarly, a single antigen could cause multiple waves of seroconversion with different classes of antibodies. For example, most antigens prompt seroconversion for the IgM class of antibodies first, and subsequently the IgG class.

Rheumatoid factor (RF) is the autoantibody that was first found in rheumatoid arthritis. It is defined as an antibody against the Fc portion of IgG and different RFs can recognize different parts of the IgG-Fc. RF and IgG join to form immune complexes that contribute to the disease process such as chronic inflammation and joint destruction at the synovium and cartilage.

<span class="mw-page-title-main">Widal test</span> Presumptive serological test for enteric fever or undulant fever

The Widal test, developed in 1896 and named after its inventor, Georges-Fernand Widal, is an indirect agglutination test for enteric fever or undulant fever whereby bacteria causing typhoid fever is mixed with a serum containing specific antibodies obtained from an infected individual. In cases of Salmonella infection, it is a demonstration of the presence of O-soma false-positive result. Test results need to be interpreted carefully to account for any history of enteric fever, typhoid vaccination, and the general level of antibodies in the populations in endemic areas of the world. As with all serological tests, the rise in antibody levels needed to perform the diagnosis takes 7–14 days, which limits its applicability in early diagnosis. Other means of diagnosing Salmonella typhi (and paratyphi) include cultures of blood, urine and faeces. These organisms produce H2S from thiosulfate and can be identified easily on differential media such as bismuth sulfite agar. Typhidot is the other test used to ascertain the diagnosis of typhoid fever. A new serological test called the Tubex test is neither superior nor better performing than the Widal test. Therefore, Tubex test is not recommended for diagnosis of typhoid fever.

The direct and indirect Coombs tests, also known as antiglobulin test (AGT), are blood tests used in immunohematology. The direct Coombs test detects antibodies that are stuck to the surface of the red blood cells. Since these antibodies sometimes destroy red blood cells they can cause anemia; this test can help clarify the condition. The indirect Coombs test detects antibodies that are floating freely in the blood. These antibodies could act against certain red blood cells; the test can be carried out to diagnose reactions to a blood transfusion.

<span class="mw-page-title-main">Serotype</span> Distinct variation within a species of bacteria or virus or among immune cells

A serotype or serovar is a distinct variation within a species of bacteria or virus or among immune cells of different individuals. These microorganisms, viruses, or cells are classified together based on their surface antigens, allowing the epidemiologic classification of organisms to a level below the species. A group of serovars with common antigens is called a serogroup or sometimes serocomplex.

<span class="mw-page-title-main">Agglutination (biology)</span> Type of antibody response

Agglutination is the clumping of particles. The word agglutination comes from the Latin agglutinare.

<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.

Autoimmune hemolytic anemia (AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to an insufficient number of oxygen-carrying red blood cells in the circulation. The lifetime of the RBCs is reduced from the normal 100–120 days to just a few days in serious cases. The intracellular components of the RBCs are released into the circulating blood and into tissues, leading to some of the characteristic symptoms of this condition. The antibodies are usually directed against high-incidence antigens, therefore they also commonly act on allogenic RBCs. AIHA is a relatively rare condition, with an incidence of 5–10 cases per 1 million persons per year in the warm-antibody type and 0.45 to 1.9 cases per 1 million persons per year in the cold antibody type. Autoimmune hemolysis might be a precursor of later onset systemic lupus erythematosus.

Paroxysmal cold hemoglobinuria (PCH) or Donath–Landsteiner hemolytic anemia (DLHA) is an autoimmune hemolytic anemia featured by complement-mediated intravascular hemolysis after cold exposure. It can present as an acute non-recurrent postinfectious event in children, or chronic relapsing episodes in adults with hematological malignancies or tertiary syphilis. Described by Julius Donath (1870–1950) and Karl Landsteiner (1868–1943) in 1904, PCH is one of the first clinical entities recognized as an autoimmune disorder.

Cold agglutinin disease (CAD) is a rare autoimmune disease characterized by the presence of high concentrations of circulating cold sensitive antibodies, usually IgM and autoantibodies that are also active at temperatures below 30 °C (86 °F), directed against red blood cells, causing them to agglutinate and undergo lysis. It is a form of autoimmune hemolytic anemia, specifically one in which antibodies bind red blood cells only at low body temperatures, typically 28–31 °C.

An agglutinin is a substance in the blood that causes particles to coagulate and aggregate; that is, to change from fluid-like state to a thickened-mass (solid) state.

In the diagnostic laboratory, virus infections can be confirmed by a myriad of methods. Diagnostic virology has changed rapidly due to the advent of molecular techniques and increased clinical sensitivity of serological assays.

<span class="mw-page-title-main">Heterophile antibody test</span> Diagnosistic test for infectious mononucleosis

The mononuclear spot test or monospot test, a form of the heterophile antibody test, is a rapid test for infectious mononucleosis due to Epstein–Barr virus (EBV). It is an improvement on the Paul–Bunnell test. The test is specific for heterophile antibodies produced by the human immune system in response to EBV infection. Commercially available test kits are 70–92% sensitive and 96–100% specific, with a lower sensitivity in the first two weeks after clinical symptoms begin.

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

In molecular biology, hemagglutinins are receptor-binding membrane fusion glycoproteins produced by viruses in the Paramyxoviridae and Orthomyxoviridae families. Hemagglutinins are responsible for binding to receptors on red blood cells to initiate viral attachment and infection. The agglutination of red cells occurs when antibodies on one cell bind to those on others, causing amorphous aggregates of clumped cells.

<span class="mw-page-title-main">Red cell agglutination</span> Clumping of red blood cells

In hematology, red cell agglutination or autoagglutination is a phenomenon in which red blood cells clump together, forming aggregates. It is caused by the surface of the red cells being coated with antibodies. This often occurs in cold agglutinin disease, a type of autoimmune hemolytic anemia in which people produce antibodies that bind to their red blood cells at cold temperatures and destroy them. People may develop cold agglutinins from lymphoproliferative disorders, from infection with Mycoplasma pneumoniae or Epstein–Barr virus, or idiopathically. Red cell agglutination can also occur in paroxysmal nocturnal hemoglobinuria and warm autoimmune hemolytic anemia. In cases of red cell agglutination, the direct antiglobulin test can be used to demonstrate the presence of antibodies bound to the red cells.

The Vel blood group is a human blood group that has been implicated in hemolytic transfusion reactions. The blood group consists of a single antigen, the high-frequency Vel antigen, which is expressed on the surface of red blood cells. Individuals are typed as Vel-positive or Vel-negative depending on the presence of this antigen. The expression of the antigen in Vel-positive individuals is highly variable and can range from strong to weak. Individuals with the rare Vel-negative blood type develop anti-Vel antibodies when exposed to Vel-positive blood, which can cause transfusion reactions on subsequent exposures.

<span class="mw-page-title-main">Blood compatibility testing</span> Testing to identify incompatibilities between blood types

Blood compatibility testing is conducted in a medical laboratory to identify potential incompatibilities between blood group systems in blood transfusion. It is also used to diagnose and prevent some complications of pregnancy that can occur when the baby has a different blood group from the mother. Blood compatibility testing includes blood typing, which detects the antigens on red blood cells that determine a person's blood type; testing for unexpected antibodies against blood group antigens ; and, in the case of blood transfusions, mixing the recipient's plasma with the donor's red blood cells to detect incompatibilities (crossmatching). Routine blood typing involves determining the ABO and RhD type, and involves both identification of ABO antigens on red blood cells and identification of ABO antibodies in the plasma. Other blood group antigens may be tested for in specific clinical situations.

<span class="mw-page-title-main">Antibody elution</span> Laboratory procedure

An antibody elution is a clinical laboratory diagnostic procedure which removes sensitized antibodies from red blood cells, in order to determine the blood group system antigen the antibody targets. An antibody elution is deemed necessary when antibodies of the immunoglobulin class G (IgG) are found sensitized (bound) to peripheral red cells collected from a blood product transfusion recipient. IgG antibodies are detected using an assay known as the direct antiglobulin test.

References

  1. 1 2 Ryan KJ, Ray CG, eds. (2004). Sherris Medical Microbiology (4th ed.). McGraw Hill. pp.  247–9. ISBN   978-0-8385-8529-0.
  2. ↑ Washington JA (1996). "Principles of Diagnosis: Serodiagnosis". In Baron S, et al. (eds.). Baron's Medical Microbiology (4th ed.). Univ of Texas Medical Branch. ISBN   978-0-9631172-1-2.
  3. ↑ Gardner, Ross M. (2011). Practical crime scene processing and investigation (Second ed.). CRC Press.
  4. ↑ "Enzyme-linked immunosorbent assay (ELISA)". British Society for Immunology.
  5. ↑ Atmar, Robert L. (2014), "Immunological Detection and Characterization", Viral Infections of Humans, Boston, MA: Springer US, pp. 47–62, doi:10.1007/978-1-4899-7448-8_3, ISBN   978-1-4899-7447-1, S2CID   68212270 , retrieved 2021-06-13
  6. 1 2 3 Mary Louise Turgeon (10 February 2015). Linne & Ringsrud's Clinical Laboratory Science - E-Book: The Basics and Routine Techniques. Elsevier Health Sciences. pp. 586–95, 543, 556. ISBN   978-0-323-37061-5.
  7. 1 2 Frank E. Berkowitz; Robert C. Jerris (15 February 2016). Practical Medical Microbiology for Clinicians. John Wiley & Sons. pp. 24–25. ISBN   978-1-119-06674-3.
  8. ↑ Connie R. Mahon; Donald C. Lehman; George Manuselis (18 January 2018). Textbook of Diagnostic Microbiology - E-Book. Elsevier Health Sciences. pp. 193–4. ISBN   978-0-323-48212-7.
  9. 1 2 Denise M Harmening (30 November 2018). Modern Blood Banking & Transfusion Practices. F.A. Davis. pp. 65, 261. ISBN   978-0-8036-9462-0.
  10. ↑ American Association for Clinical Chemistry (24 December 2019). "Direct Antiglobulin Test". Lab Tests Online. Retrieved 24 April 2020.
  11. ↑ Richard A. McPherson; Matthew R. Pincus (6 September 2011). Henry's Clinical Diagnosis and Management by Laboratory Methods. Elsevier Health Sciences. pp. 714–5. ISBN   978-1-4557-2684-4.
  12. ↑ American Association for Clinical Chemistry (13 November 2019). "Autoantibodies". Lab Tests Online. Retrieved 24 April 2020.
  13. ↑ Metcalf, C Jessica E.; Farrar, Jeremy; Cutts, Felicity T.; Basta, Nicole E.; Graham, Andrea L.; Lessler, Justin; Ferguson, Neil M.; Burke, Donald S.; Grenfell, Bryan T. (2016). "Use of serological surveys to generate key insights into the changing global landscape of infectious disease". The Lancet. 388 (10045): 728–730. doi:10.1016/S0140-6736(16)30164-7. PMC   5678936 . PMID   27059886.
  14. ↑ De Lusignan, Simon; Correa, Ana (2017). "Opportunities and challenges of a World Serum Bank". The Lancet. 389 (10066): 250–251. doi:10.1016/S0140-6736(17)30046-6. PMID   28118910. S2CID   42914918.
  15. ↑ Coates, Karen M. (2017). "Opportunities and challenges of a World Serum Bank". The Lancet. 389 (10066): 251–252. doi: 10.1016/S0140-6736(17)30052-1 . PMID   28118912.
  16. ↑ "WHO set pandemic response back by 2-3 weeks, says doctor on new federal task force". CBC. 23 April 2020.
  17. ↑ "Prime Minister announces new support for COVID-19 medical research and vaccine development". Justin Trudeau, Prime Minister of Canada. 23 April 2020.
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