Cytomegalovirus (CMV) Antibodies, IgG

In the United States, nearly one in three children is already infected with CMV by age 5, and more than half of adults have been infected by age 40. Primary CMV infection in immunocompetent individuals typically follows an asymptomatic or subclinical course. Mononucleosis is the most prevalent presentation of CMV in patients with an intact immune system, characterized by fever, rash and lymphocytosis. Immunocompromised individuals, infants infected in utero, and low birth weight and premature infants are at higher risk for serious complications from CMV infection, both primary and reactivation. Infection in these groups can impact multiple organ systems and is associated with increased morbidity. CMV is the most common congenital infection, and the risk of CMV complications (e.g., birth defects including hearing loss) in the fetus is greatest if a primary infection occurs during the first trimester. In infants, children and adults, viremia can be detected for two to three weeks after a primary infection, and IgM becomes detectable at about 28 to 60 days followed by a detectable IgG antibody response.

Nucleic acid amplification testing is recommended for the diagnosis of congenital CMV in newborns (up to 12-18 months) and for monitoring infection in transplant recipients. In individuals older than 12 months, including pregnant individuals, a positive CMV IgG test indicates infection with CMV at some time during their life but does not indicate when they were infected. Measurement of CMV IgG in paired samples taken one to three months apart can be used to diagnose primary infection. Seroconversion (acute serum IgG negative, convalescent serum IgG positive) is evidence of primary infection. The clinical utility of CMV IgM is more limited as the detection of CMV IgM in itself cannot be used to diagnose primary CMV infection because IgM can also be present during secondary CMV infection and reactivation. IgM positive results in combination with low IgG avidity results are considered reliable evidence for primary infection.

For more detailed differentiation of primary and past infections, IgG avidity assays are useful. IgG avidity assays measure the binding strength between IgG antibodies and virus and can help distinguish a primary CMV infection from a past infection. Following primary CMV infection, IgG antibodies have low binding strength (low avidity), then within two to four months they mature to high binding strength (high avidity). While commercial assays for avidity testing are available, they need further standardization and should be interpreted with caution.