Cytomegalovirus (CMV) IgG avidity

CMV IgM appears within the first 1 to 2 weeks after primary (new) infection; CMV IgG appears 1 to 2 weeks after IgM is detectable. IgG levels peak by 2 to 3 months post-infection and usually remain detectable for life. In about 75% of individuals, the IgM level gradually decreases to undetectable by 4 months after infection; however, in about 25% of individuals, IgM remains detectable for more than a year following infection. Another confounding concern about CMV IgM is that virus reactivation months or years after primary infection may cause IgM to reappear. Thus, an IgG-positive, IgM-positive result set is not a reliable indicator of recent primary CMV infection. 

Avidity is defined as the aggregate strength with which antibodies bind to antigen. IgG avidity gradually matures over time; IgG antibodies produced during the first few months following primary infection exhibit low avidity (ie, they bind weakly to the antigen), whereas antibodies produced by 6 months after infection exhibit high avidity (ie, they bind tightly to the antigen).

The CMV IgG avidity assay aids in discriminating recent from past CMV infection, particularly in pregnant women. Women who become infected with CMV after conception are much more likely to transmit the infection to the baby, compared to women who were already infected (ie, have circulating CMV IgG antibodies) at the time of conception. Unfortunately, less than 5% of women undergo pre-conception screening for CMV antibodies, so their CMV antibody status becomes known only when they are tested due to concerns about the fetus. If the mother is positive for both CMV IgG and IgM, it is important to perform CMV IgG avidity testing to determine if the positive antibody results represent what is more likely a recent (after conception) infection or more likely a past (before conception) infection. 

The patient’s serum is added to the assay in duplicate. After incubation to allow IgG in the serum to bind to the CMV antigen, one duplicate is treated with urea (low avidity IgG antibodies dissociate from the antigen in the presence of this reagent), and the other duplicate is treated with a control reagent. The assay is then finished and the signal of the urea-treated sample is divided by the signal of the control-treated sample, giving an avidity index. Avidity index values <0.60 are interpreted as low avidity, and values >0.70 are interpreted as high avidity; values from 0.60 to 0.70 (inclusive) are interpreted as intermediate avidity.

It depends on the trimester in which the mother’s specimen was collected for CMV IgG avidity testing. In most cases, an intermediate avidity result in the first trimester is comparable to a high avidity result, whereas an intermediate avidity result in the second or third trimester is comparable to a low avidity result; however, the

intermediate avidity result should be considered within the context of all available clinical and laboratory information.

No. The avidity of CMV IgG can only be measured in samples that are positive for CMV IgG.

Not in most cases. A CMV IgG-positive, IgM-negative reactivity pattern is a reliable indicator of past infection. However, a small number of recent CMV infections exhibiting an IgG-positive, IgM-negative reactivity pattern have been described.¹ Thus, submitting such samples for CMV IgG avidity may be warranted if the index of suspicion is high.

No laboratory test is 100% accurate; thus, there is a small chance that a pregnant woman with a high avidity result may give birth to a CMV-infected infant. A major factor is the time during pregnancy when avidity testing is performed. Due to the timeline for development of high avidity IgG antibodies (see question 2), a high-avidity result near the end of the second trimester or any time during the third trimester does not preclude primary CMV infection soon after conception, and thus increased risk of fetal infection. However, as shown in several studies (summarized in reference 1), women with high avidity during the first trimester have a low risk of congenital transmission.