Determination of anti-p52 IgM and anti-gB IgG by ELISA as a novel diagnostic tool for detection of early and late phase of primary human cytomegalovirus infections during pregnancy

Background: Dating of primary human cytomegalovirus (HCMV) infection in pregnancy is crucial to define whether infection occurred before or during pregnancy and at which gestational age. Objective: The aim of this study was to identify a diagnostic strategy for determination of early, intermediate and late phase of HCMV primary infection during pregnancy. Study design: Sequential serum samples from 40 pregnant women with defined onset of HCMV primary infection were tested retrospectively for IgM, IgG and IgG avidity against whole HCMV lysate, along with anti-p52 IgM and anti-gB IgG (Euroimmun AG). Results: Anti-HCMV IgM were positive in all samples collected within the first 2 months, then decreased remaining weakly positive in about 40% of samples collected within 6–12 months after infection. Anti-p52 IgM followed similar kinetics but decreased earlier, remaining weakly positive only in 20% of late samples. Anti-HCMV IgG were positive in all samples and showed variable kinetics. Their avidity increased from low levels, observed within 2 months, to intermediate/high levels from 4 months onwards. Anti-gB IgG increased over time following kinetics similar to anti-HCMV IgG avidity. By combining results of anti-HCMV IgM plus IgG avidity, and confirming them with anti-p52 IgM plus anti-gB IgG as second-line assays, the early (within 2–3 months) and late (after 3 months) phases of HCMV infection were satisfactorily defined, whereas the intermediate phase overlapped with the beginning of the late phase. Conclusion: Anti-p52 IgM and anti-gB IgG provide additional tools besides classical anti-HCMV IgM, IgG and IgG avidity in dating HCMV primary infections.