IMPORTANCE TORCH PANEL
IMPORTANCE TORCH PANEL
, The TORCH test is used to screen pregnant women and newborns for antibodies to the infections disease included in the panel, if either the mother or newborn has symptoms. This blood test can determine if the person has had a recent infection, a past infection, or has never been exposed. The test is ordered when a pregnant women is suspected of having any of the TORCH infections. These infections can be serious if they occur during pregnancy because they can cross the placenta from the mother to the developing fetus and can cause congenital defects in the newborn.
THE TORCH AVIDITY TEST:
The IgG avidity test was developed to help discriminate between past and recently acquired infection. Following antigenic challenge the IgG antibodies produced initially bind weakly to the antigen (low avidity). As the immune response develops there is maturation of IgG antibody response and the avidity increases progressively over weeks or months (high avidity). The avidity determination is a diagnostic method which is used to differentiate a recent (acute) and a more distant (past) infection with Toxoplasma gondii, Rubella or CMV virus in patient sera. Avidity is the binding force of the antibody (serum specimen) with the corresponding antigen.
The determination of IgG antibody avidity is an additional analysis to the classic serology in regard to the status of a infection. Depending on the method used, the avidity tests currently available are helpful primarily in establishing the fact that infection was not acquired in the previous 4-6 months. This is extremely useful in pregnancy where establishing timing of infection is critical for the management of the pregnancy. In the absence of antenatal screening this may need to be determined on a single sample. IgG antibodies persist lifelong and IgM can be detected for > 1 year after infection. Demonstrating that the IgG antibodies are of high avidity can establish that infection was acquired before conception and there should be no risk to the fetus unless there is immunocompromise.
Demonstration of low IgG avidity antibodies does not necessarily mean the patient has recently acquired infection as low avidity antibody may persist for > 1 year in some patients. The test cannot be used in very early infections, as the level of IgG antibody must be high enough to allow accurate measurement of the effect of the denaturing treatment.
High Avidity: > 40% Low Avidity: < 40%
TOXOPLASMA GONDII AVIDITY TEST
Acute Toxoplasma gondii infection in early pregnancy carries the risk of transmitting the infection to the fetus with serious sequelae. However, serological testing for IgG/IgM anti- Toxoplasma antibodies may fail to differentiate between a recent and past infection. Avidity test is a helpful tool for the diagnosis of recent Toxoplasma infection in IgM-negative women with low-avidity antibodies and IgM-positive women with high-avidity antibodies; the specificity was >85 -100%. Hence the avidity test when used in combination with IgG/IgM tests is a valuable assay for the exclusion of ongoing or recently acquired T. gondii infection in pregnant women in their first trimester and that it decreases significantly the necessity for follow-pp testing and unnecessary therapeutic intervention.
The test which is based on the measurement of the avidity of toxoplasma specific IgG antibodies, was developed by Hedman and colleagues in Finland in 1989. In the toxoplasma IgG avidity ELISA, urea or another protein denaturing agent is used to dissociate the antigen-antibody complex. The results (expressed as % avidity) reflect the extent of antigen antibody complex dissociation caused by the denaturing agent.
The test may be performed using a single serum dilution but more accurate results are obtained by titration. The toxoplasma IgG avidity test is a confirmatory test and should not be used alone.
When used appropriately and interpreted with other serological tests it is a very useful test.
RUBELLA IgG AVIDITY TEST:
The serological diagnosis of infection is based on the presence of specific IgG and IgM antibodies. More recently, assays of the avidity of Rubella IgG (i.e. the strength of IgG binding to a multivalent antigen of the virus), have been used to distinguish recent from old infections in individuals with high IgG levels. If the mother has Rubella infection in the first two weeks of gestation, there is an 80% risk of infection developing in fetus. This risk decreases to 6-10% if the infection occurs until the 14th week. The virus may cause disabilities or embryo deaths in especially the first three months of the gestation. The most prominent effects of Rubella is displayed in the organs in their sensitive development periods. At the onset of the immune response (acute phase), the IgG generated by the antigenic stimulus has low avidity (i.e. binds with less avidity to the antigen), but as time goes by in the convalescence, after the first two to four months of infection, avidity increases.
The differential diagnosis between an asymptomatic primary Rubella infection and re-infection is extremely important, yet difficult, because under both conditions antibody titres are increased and IgM may be present. The IgG level is important to indicate susceptibility to re-infection, common in women with levels below 10 IU/mL. Re-infections, for the most part asymptomatic, pose a low risk to the fetus, but they may develop with the presence of IgM, particularly in the re-infection of vaccinated women. Re-infection is suspected in a specific sample when the specific IgG is positive and the avidity of IgG is high, accompanied or not by IgM. So, avidity of IgG may be useful to distinguish between the two conditions, being low in primary infection and high in re-infection. Rubella IgG avidity test results were evaluated as high avidity for over 60% avidity, intermediate avidity for those in between 50-60%, and low avidity for avidities lower than 50%.
CMV IgG AVIDITY TEST:
Human cytomegalovirus (HCMV) is among the most important causes of congenital infections. Measurement of CMV-specific IgG avidity has proven to be a powerful tool for distinguishing primary from non-primary CMV infection. Defined as the strength with which the IgG attaches to antigen, IgG avidity matures with the length of time following primary infection. Thus, IgG produced within the first few months following primary infection exhibits low avidity, whereas IgG produced several months or years later exhibits high avidity. The most important risk in intrauterine infection is the primary or recurrent infection of the mother. In 35-50% of the pregnant women who have primary HCMV infection, intra-uterine infections develop in fetus, and 10% of the infected fetuses are born symptomatic; the severity of the clinical scene is related to the amount of virus the baby is infected with, virulence, and the gestational stage. Congenital anomalies in the fetus are more frequent in the first trimester, as organs develop in this period; and death of precursor cells may cause congenital defects.
Diagnosis of HCMV and Rubella in pregnant women is performed by detection of IgM and IgG antibodies by various serological tests. The conventional serological diagnosis of a primary infection is based on revealing IgG seroconversion along with IgM positivity. Different IgM responses may also occur against microbial antigens; specific IgM may turn negative in serum in acute infection earlier than expected, or it may be detected for months or years in low titer.
Therefore, when specific IgM positivity is detected in a serum sample, it is difficult to decide towards presence of a secondary infection as acute infection, persistent IgM or re-activation /reinfection. In the recent years, as IgG avidity tests got into the practical use, safe discrimination of primary acute infections, reactivation and/or reinfections with a single serum sample became possible. This discrimination holds clinical value especially in pregnant women and immunosupressed patients.
Avidity is a term used to describe the combined strength of multiple bond interactions. It is commonly applied to antibody interactions in which multiple antigen binding sites simultaneously interact with a target. As such, avidity is the combined synergistic strength of bond affinities rather than the sum of bonds.
Avidity is distinct from affinity, which is a term used to describe the strength of a single bond. Individually, each binding interactions are present at the same time, transient unbinding of a single site does not allow the molecule to diffuse away, and binding of that site is likely to be reinstated. The overall effect is synergistic, strong binding of antigen to antibody (e.g. IgM is said to have low affinity but high avidity because it has 10 weak binding sites as opposed to the 2 strong binding sites of IgG, IgE, and Igd).
Low avid IgG antibodies in the early stage of infection can be differentiated from high avid antibodies associated with a past infection