Introduction Human cytomegalovirus CMV is a herpesvirus whic
Human cytomegalovirus (CMV) is a herpesvirus which has a ubiquitous and worldwide distribution, and is the most frequent cause of congenital infection (Kenneson and Cannon, 2007). The prevalence is around 0.5–1% of all live births and is the leading cause of sensorineural hearing loss and mental retardation (Dollard et al., 2007, Stagno, 1986). CMV congenital infection can result from primary infection, reinfection, or reactivation among pregnant women. The risk of vertical transmission from mothers with primary infection during pregnancy ranges from 30% to 45% (Bodeus et al., 2010, Enders et al., 2011, Liesnard et al., 2000, Picone et al., 2013, Revello et al., 2011), and the risk is going down to 1.4% in case of nonprimary infection (Kenneson and Cannon, 2007). In order to counsel about the fetal risk, it merestinib is of major importance to differentiate CMV primary infections occurring before pregnancy from those occurring during pregnancy. The maternal infection is mostly asymptomatic, and when symptoms are present, they are mostly mild (Daiminger et al., 2005). Particularly before 12–14 weeks of gestation, the presence of IgG and IgM without knowing about the previous serologic status can be a source of anxiety for parents and of difficult management for professionals. Supplementary tests are then needed to define primary infection onset. IgG avidity assays are widely used in case of positive IgG and IgM in pregnant women. These tests determine the strength of antigen–antibody bond, which increases over time after the primary infection. The IgG avidity is initially low during the early weeks and will mature to high avidity a few months after primary infection (Prince and Lapé-Nixon, 2014). In 12–25% of cases, the result of these conventional IgG avidity assays is inconclusive (intermediate avidity index); therefore, other markers are needed to help to date the onset of CMV primary infection (Enders et al., 2014, Leruez-Ville et al., 2013, Prince and Lapé-Nixon, 2014). Recently, other assays such as reactivity against specific CMV antigens and neutralizing antibodies were reported as additional tools for dating the onset of primary infection in pregnancy (Enders et al., 2013, Lilleri et al., 2016).
In this study, we aimed first to evaluate the ability of the line immunoassays Mikrogen recomLine CMV IgG and recomLine CMV IgG Avidity (Mikrogen GmbH, Neuried, Germany) to date the onset of CMV primary infection comparing to VIDAS CMV IgG Avidity (bioMérieux, Marcy l\'Etoile, France) and, secondly, to evaluate the added value of the combination of recomLine CMV IgG and recomLine CMV IgG Avidity in cases of intermediate VIDAS avidity.
Discussion In this study, we evaluated the performance of the recomLine IgG and IgG Avidity with a total of 178 samples. Half of them came from women with precisely determined onset of CMV primary infection, and half of them were sera with an intermediate VIDAS IgG avidity. CMV IgG avidity tests are widely used as a useful tool to date CMV infection, especially in pregnant women presenting with positive CMV IgG and IgM, but they are not standardized (Revello et al., 2010). Several comparative studies have shown discrepancies between commercial assays, in particular false high positive results (Revello et al., 2010, Sellier et al., 2015, Vauloup-Fellous et al., 2013). We also observed a false high positive result in this study, previously described as a case report (Delefortrie et al., 2016). Other limitations are, on the one hand, the restricted usefulness of these tests after the first trimester of pregnancy and, on the other hand, the reported unusually long persistence of intermediate or low CMV IgG avidity in some cases (Lumley et al., 2014, Revello et al., 2010, Sellier et al., 2015, Vauloup-Fellous et al., 2013). Therefore, we have to be cautious with their interpretation, and other tests such as immunoblot assays may be useful in this setting.