Avidity - What Is It? IgG Antibody Avidity

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Avidity - What Is It? IgG Antibody Avidity
Avidity - What Is It? IgG Antibody Avidity

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Video: Affinity and Avidity (Antigen antibody interaction) 2023, February
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Avidity (Latin - avidity) is a characteristic of the strength of the binding of specific antibodies with the corresponding antigens. Currently, there are many diagnostic methods for detecting infectious diseases: toxoplasmosis, hepatitis, cytomegalovirus. Avidity allows you to understand at what stage the infection is and how successfully the immune system fights it.

The content of the article:

  • 1 What is avidity
  • 2 Avidity index
  • 3 Types of avidity
  • 4 The clinical significance of the definition of low-avid bodies

    • 4.1 Toxoplasmosis
    • 4.2 Herpes simplex virus infections
    • 4.3 Viral hepatitis C
  • 5 Toxoplasma during pregnancy

What is avidity

Avidity - what is it? IgG antibody avidity
Avidity - what is it? IgG antibody avidity

In the course of the body's immune response to the penetration of an infectious agent, the stimulated clone of lymphocytes begins to produce first specific IgM antibodies, and somewhat later, specific IgG antibodies. IgG antibodies initially have low avidity, that is, they bind the antigen rather weakly. Then the development of the immune process gradually (it can be weeks or months) goes towards the synthesis of highly avid IgG antibodies by lymphocytes, which bind more firmly to the corresponding antigens. The high avidity of specific IgG antibodies excludes recent primary infection.

Confirmation or exclusion of the fact of recent primary infection with Toxoplasma gondii and Cytomegalovirus is especially important when examining pregnant women, since the risk of fetal pathology is significantly increased with acute primary infection during pregnancy, compared with chronic infection and reactivation of latent infection.

Therefore, there is a constant search for new diagnostic approaches that allow the most reliable assessment of the stage and form of the infectious process. The use of the avidity of IgG antibodies as an indicator of the period of primary infection, first proposed by Finnish researchers (Hedman KM et al., 1989), is currently introduced into the practice of serological studies for TORCH infection in a number of countries.

So, in France, where, as in Russia, the problem of toxoplasmosis is still relevant, this test is included in the mandatory examination algorithm for suspected toxoplasmosis in pregnant women.

Detection in the serum of the presence of both IgG and IgM antibodies to an infectious agent can be interpreted as evidence of a recent primary infection, since, as you know, the disappearance of IgM antibodies is usually about 3 months from the onset of the infectious process. But the period of circulation of IgM antibodies can vary significantly depending on the infectious agent and the individual characteristics of the body's immune response. When infected with Toxoplasma gondii and Cytomegalovirus, trace amounts of IgM antibodies to these infectious agents in some cases are detected within 1 - 2 or more years.

Avidity - what is it? IgG antibody avidity
Avidity - what is it? IgG antibody avidity

Thus, their presence in the blood of a pregnant woman is not always a confirmation of primary infection during pregnancy. In addition, the specificity of even the best commercial IgM test systems is not absolute. In some situations, as a consequence of the very high sensitivity of the tests, nonspecific false positive results are possible. The detection of highly avid IgG antibodies in the blood in this situation makes it possible to exclude a recent primary infection. Low avian IgG antibodies, on average, are detected within 3 to 5 months from the onset of infection (this may, to a certain extent, depend on the method of determination), but sometimes they are produced for a longer period. By itself, the detection of low-avidity IgG antibodies is not an unconditional confirmation of the fact of fresh infection,but serves as additional confirmatory evidence in a number of other serological tests. When the infection is reactivated, specific IgGs of high avidity are detected.

Indications for the purpose of the test. In a complex of serological tests for the diagnosis of toxoplasmosis and cytomegalovirus infection - when positive results of IgG and IgM antibodies are detected (in order to exclude or confirm the likelihood of recent primary infection).

Preparation for research: not required.

Research method. These tests are based on a method for differentiating high and low avidity antibodies by treating antigen-antibody complexes with a urea solution, which causes protein denaturation. After such treatment, the connection of low avidity antibodies with the antigen is broken.

The avidity of IgG antibodies in a sample is assessed using the calculated avidity index, which is the ratio of the result of the enzyme immunoassay of the concentration of IgG antibodies in a sample treated with urea to the result of measuring the concentration of IgG antibodies in a sample not treated with a dissociating agent.

Units of Measurement: Results are reported as Avidity Index.

Avidity index

Avidity - what is it? IgG antibody avidity
Avidity - what is it? IgG antibody avidity

For laboratory diagnostics, the avidity of igg antibodies is important, since it makes it possible to determine when a patient was infected. The avidity of igg antibodies to toxoplasma gondii is quantified using an index that is expressed in fractions or percentages.

The Toxoplasma avidity index shows the number of antibodies out of a hundred that bind tightly to Toxoplasma membranes.

Types of avidity

The avidity of igg antibodies to toxoplasmosis has three options:

  • High when the index is above 40% (0.4). It means that toxoplasmosis was transferred at least four months ago. In this case, it can be argued that a person has a powerful immune defense against re-infection.
  • Low - less than 30% (0.3). This indicates that less than three months have occurred since the initial infection. Antibodies are gradually destroyed, and they are replaced by immunocompetent cells, a highly avid species, which remains in the body throughout life.
  • Medium (gray zone) - 31-40% (0.3-0.4). These antibodies are transitional, since both varieties circulate in the human blood simultaneously, which makes it impossible to accurately determine the duration of infection. Thus, the patient needs to be tested again after two to four weeks.

Clinical Significance of Identifying Low Avid Bodies

Application of the method for determining the avidity of antibodies is of interest in the diagnosis of infections.

Rubella has an undeniable teratogenic effect, i.e. leads to the formation of malformations of the embryo and fetus. In pregnant women, rubella can be severe, mild, and asymptomatic. Intrauterine infection of the fetus is possible with any form of rubella infection. Recognizing an infection, especially during an outbreak, is not difficult.

However, an accurate diagnosis requires virus isolation, which is not always technically feasible.

Laboratory diagnosis usually consists in the determination of IgG and IgM antibodies, mainly in pregnant women, since the risk of giving birth to an inferior or stillborn child in an infected mother is very high and termination of pregnancy is usually recommended. However, antibody-based diagnostics can produce false positive and false negative results.

So, with repeated infection in vaccinated, which can occur in cases of a low immune response during vaccination, or can be caused by mutant strains of the virus, IgM antibodies are not formed, an increase in IgG antibody titers is also not always observed. In newborns with primary infection due to intrauterine infection, IgM antibodies may not be synthesized for a number of reasons:

  • immaturity of the immune system;
  • blocking the viral antigen by maternal antibodies;
  • infection in the late stages of pregnancy;
  • immune tolerance.

If rubella virus lymphocyte clones are stimulated, a false positive antibody response may occur, especially for antibodies of the IgM class. It has been shown that IgM antibodies can persist for a year or occur in cases of reinfection, especially in immunosuppressive patients.

In addition, false positive results may occur due to the presence of rheumatoid factor or similar compounds, even in a trap test.

Only the determination of low avidity antibodies can be a diagnostic marker of primary infection with the rubella virus, which is especially important in the diagnostic examination of pregnant women, when it is necessary to differentiate the primary infection from the secondary or reactivation of the infection.

Toxoplasmosis

Avidity - what is it? IgG antibody avidity
Avidity - what is it? IgG antibody avidity

It is known that the manifestation of clinical symptoms in acquired toxoplasmosis has a low diagnostic value for accurately determining the duration of the infectious process.

The enlargement of lymph nodes can occur at different times from the moment of the primary infection, and often it can persist for a long time or even resume in a later period of the disease, regardless of the use of specific antiparasitic treatment.

Until now, the only available serological tests for the determination of the acute phase of toxoplasmosis have been the determination of IgM antibodies and the determination of IgG antibodies in increasing titers in two or three serum samples, which, however, leads to a delay in the diagnosis.

In addition, in patients with reactivation of chronic toxoplasmosis, a significant increase in the level of IgG antibodies is not always observed, especially in children and adolescents with eye damage with congenital toxoplasmosis.

Interpretation of the results of studies of other immunoglobulins is also difficult. The main disadvantage of the determination of IgM antibodies is long-term persistence in the blood, which makes it difficult to establish the end of the acute phase of the disease. In 40% of patients, IgM antibodies are detected within a year from the moment of infection using ELISA, in 60% - using a highly sensitive method of immunoadsorption. As well as IgM, specific IgA was present in peripheral serum 45 months after the reported seroconversion, during the 2-year serologic follow-up period, and 8 months after the onset of signs of lymphadenopathy. On the other hand, in certain categories of patients, for example, in children, IgM antibodies are not formed at all.

The determination of the avidity of IgG antibodies is a highly specific and sensitive method for diagnosing acute primary toxoplasmosis, which is especially important when examining pregnant women to eliminate the potential risk of congenital toxoplasmosis in children.

Recently, a technique has been developed to measure the antigen-binding avidity (functional affinity) of IgG antibodies to Toxoplasma gondii, which distinguishes low-affinity antibodies from high-affinity antibodies that indicate past infection. With this technique, the primary infection can be identified using a single serum.

Herpes simplex virus infections

The frequency of infection of newborns in women with a subclinical form of herpes simplex is 3-5% with chronic infection and reaches 30-50% with infection during pregnancy (primary infection). Infections caused by herpes simplex viruses, cytomegalovirus refer to infections with atypical dynamics of antibody production (when the presence of IgM is not reliable and sufficient to differentiate the stages of the disease). Determination of IgM antibodies can give false negative results because they may not be produced at all, or be present in quantities that are difficult to detect.

False positive results can occur for the following reasons:

  • long-term persistence of IgM antibodies or their presence may not be associated with infection;
  • IgM antibodies can be detected upon reactivation of an infection or upon a secondary infection, for example, with human immunodeficiency virus;
  • different viruses can share epitopes (eg, herpes simplex virus and varicella-zoster virus), which leads to cross-reactions.

Diagnostics of the active phase of infection by a 4-fold increase in the IgG titer can also cause difficulties, since the IgG antibody titer can increase quite quickly (within 1-2 days) after the onset of symptoms of the disease.

Thus, the determination of serological markers for these infections cannot serve as a specific test for differentiating between primary infection and reactivation.

High avidity
High avidity

Infection with the herpes simplex virus (HSV) leads to lifelong persistence with the possibility of virus reactivation and cross-infection with another HSV serotype. The predominance of chronic and asymptomatic forms of the course of the disease, as well as the possibility of atypical manifestations, casts doubt on the diagnosis by external signs. Approximately 20% of people with HSV-2 have no symptoms at all, and 60% of people have symptoms that cannot be diagnosed and that are not accepted by the doctor and the patients themselves for herpes (atypical manifestations). Both of these groups are at risk of infecting their partners. Specific IgM cannot be used as a reliable marker for the diagnosis of acute and, especially, primary infection, since IgM to HSV can be formed both during primary infection and during reinfection and reactivation of the virus,but at the same time, they are capable of being produced in an amount sufficient for diagnosis in only 30% of people.

The only way to immediately and reliably diagnose a primary infection is to determine the avidity index of specific antibodies

Cytomegalovirus infection (CMVI) is the most common intrauterine infection and one of the most common causes of miscarriage. The risk of intrauterine infection and the nature of fetal damage depend on the presence of antibodies in the mother and the timing of the infection of the fetus. With primary infection of a seronegative pregnant woman, the risk of transmission to the fetus is approximately 50%.

The diagnosis of primary CMVI is usually based on the determination of seroconversion, the presence of a high titer of specific IgM, or a fourfold increase in the titer of specific IgG. Due to the fact that the moment of seroconversion and an increase in IgG titers are difficult to diagnose, IgM antibodies are the most commonly used marker for the diagnosis of acute infection.

However, in some patients, IgM antibodies persist for a long time, which leads to overdiagnosis of an acute infection.

The determination of the avidity of IgG antibodies is considered the most important serological marker, since low- and high-avidity IgG antibodies are dominant, respectively, in recent or long-term infection.

The use of an IgG avidity test with a positive reaction to IgM antibodies helps to confirm or exclude the presence of primary CMVI and in some cases helps to avoid unnecessary invasive procedures.

Viral hepatitis C

Avidity - what is it? IgG antibody avidity
Avidity - what is it? IgG antibody avidity

Laboratory diagnosis of hepatitis C (HCV) is based on the identification of specific markers of infection (IgM and IgG antibodies to HCV, HCV RNA). The IgM response in the acute phase of hepatitis C does not follow the classical pathway of antibody production: anti-HCV IgM can be detected simultaneously and even later than anti-HCV IgG class. Therefore, the detection of anti-HCV IgM cannot be used as a marker of acute HCV infection. At the same time, the duration of the circulation of anticorrosive-lgM (3-5 months) is a factor predicting persistent infection, and their appearance in chronic hepatitis C indicates reactivation of the virus, i.e. exacerbation of the process. Seroconversion is the only reliable factor in confirming primary HCV infection.

The IgG avidity index in primary HCV infection has low values ​​and increases over time, which confirms the feasibility of using the IgG avidity determination of antibodies for the differential diagnosis of primary infection from chronic or previous hepatitis C.

Toxoplasma during pregnancy

Toxoplasma avidity analysis is of great importance during pregnancy, since the risk of fetal development abnormalities is especially high in primary infection compared to chronic or latent form.

If during pregnancy a woman is diagnosed with Toxoplasma, then there is little chance of giving birth to a full-fledged person. But all subsequent children will be protected by the formed antibodies.

It is advisable to conduct an examination when planning a pregnancy. If IgG is detected when decoding the results, the fetus will be protected. If the result is negative, then you need to be careful to carry out all preventive measures.

Deciphering the analysis in infants has its own specifics and allows you to determine the presence or absence of congenital toxoplasmosis.

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