Strong Cell-Mediated Immune Response to Human Cytomegalovirus Is Associated With Increased Risk of Fetal Infection in Primarily Infected Pregnant Women

• Published in: Clinical infectious diseases Vol. 61; no. 8; pp. 1228 - 1234
• Main Authors: Saldan, Alda, Forner, Gabriella, Mengoli, Carlo, Gussetti, Nadia, Palù, Giorgio, Abate, Davide
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 15.10.2015
• Subjects: Adolescent; Adult; Amniotic Fluid - virology; Antibodies, Viral - immunology; Antibody Affinity; ARTICLES AND COMMENTARIES; Biomarkers; Cytomegalovirus; Cytomegalovirus - immunology; Cytomegalovirus Infections - congenital; Cytomegalovirus Infections - diagnosis; Cytomegalovirus Infections - immunology; Cytomegalovirus Infections - transmission; Disease transmission; Enzyme-Linked Immunospot Assay; Enzymes; Female; Fetal Diseases - diagnosis; Fetal Diseases - virology; Humans; Immunity, Cellular; Immunoassay; Immunoglobulin G - immunology; Immunoglobulin M - immunology; Immunoglobulins; Infectious Disease Transmission, Vertical; Infectious diseases; Maternal & child health; Pregnancy; Pregnancy Complications, Infectious - epidemiology; Pregnancy Complications, Infectious - immunology; Regression Analysis; Risk Factors; ROC Curve; Young Adult; fetal infection; ELISPOT; human cytomegalovirus; pregnancy; cell-mediated immunity
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/civ561

Background. Human cytomegalovirus (CMV) represents one of the leading causes of congenital infections worldwide. Early diagnosis of fetal infection and consequent rapid therapeutic intervention with immunoglobulin treatment may prevent fetal transmission and virus-related sequelae. In this study, the cell-mediated immunity and immunoglobulin avidity were evaluated as potential predictors of congenital transmission of the infection. Methods. CMV immunoglobulin G (IgG) avidity and CMV enzyme-linked immunospot (ELISpot) assays were employed in 80 pregnant women including 57 primary and 23 nonprimary CMV infections. Congenital infection was assessed using CMV DNA quantitative polymerase chain reaction on amniotic fluid or offspring urine. Logistic regression and receiver operating characteristic statistical methods were employed to determine the association with congenital infection. Results. Low CMV IgG avidity (25%) alone correlated with a probability of congenital transmission of 18.2% (95% confidence interval, 7.7%–28.8%). In contrast to the expectations, an increase in CMV ELISpot levels was statistically associated with congenital transmission (P = .006). The combined use of CMV ELISpot and low CMV IgG avidity resulted in a higher level of association than either method alone with the incidence of fetal transmission (area under the curve, 0.8685). Conclusions. CMV-specific cell-mediated immunity represents a relevant marker in assessing the likelihood of congenital CMV transmission, particularly in combination with CMV IgG avidity.