Interpretive Handbook

Cytomegalovirus (CMV) is a significant cause of morbidity and mortality, especially in organ transplant recipients and individuals with AIDS. (1,2) CMV is also responsible for congenital disease of the newborn. The most common infections with CMV in immunocompromised hosts result from reactivation of the virus (latent) from a previous infection, transmission of the virus from a donor organ or blood product, or initial or primary contact with the virus in a seronegative patient. Infection in immunologically normal patients can cause mononucleosis similar to that produced by infection with Epstein-Barr virus.

Diagnosis of primary, acute phase infection with cytomegalovirus (CMV), especially in patients with infectious mononucleosis and pregnant women who, based on clinical signs or exposure, may have primary CMV infection

Determining whether a patient (especially organ donors, blood donors, and prospective transplant recipients) had CMV infection in the past

IgG:

Individuals with negative cytomegalovirus (CMV) IgG results are presumed to have not experienced infection with CMV and, therefore, are susceptible to primary infection.

Positive CMV IgG results indicate past or current CMV infection. Such individuals are potentially at risk of transmitting CMV infection through blood products; the likelihood of transmission by other modes is not known.

A ratio of > or =2 in paired sera (acute and convalescent) IgG values, along with a convalescent antibody level of >6, indicates a seroconversion has occurred and may be indicative of a recent infection.

CMV infections are quite common. Approximately 60% to 85% of the population is believed to be infected by age 18.

IgM:

Negative CMV IgM results suggest that an individual is not experiencing a recent infection. However, a negative result does not rule out primary CMV infection. It has been reported that CMV-specific IgM antibody was not detectable in 10% to 30% of cord blood sera from infants demonstrating infection in the first week of life. In addition, up to 23% (3/13) of pregnant women with primary CMV infection did not demonstrate detectable CMV IgM responses within 8 weeks post-infection. In cases of primary infection where the time of seroconversion is not well defined, as high as 28% (10/36) of pregnant women did not demonstrate CMV IgM antibody.

Positive CMV IgM results indicate a recent infection (primary, reactivation, or reinfection).

IgM antibody responses in secondary (reactivation) CMV infections have been demonstrated in some CMV mononucleosis patients, in a few pregnant women, and in renal and cardiac transplant patients. Levels of antibody may be lower in transplant patients with secondary rather than primary infections.

Sera drawn very early in the acute stage of disease may have IgG levels <4 AU/mL.

The VIDAS cytomegalovirus (CMV) IgG assay demonstrates a linear dilution response to concentration. However, no international standard has been established.

The IgG titer of a single specimen should not be used to aid in the diagnosis of recent infection. Paired (acute and convalescent) specimens should be drawn and tested concurrently to look for seroconversion which may be indicative of primary or recent infection or of reactivation of a pre-existing latent process with active viral excretion.

Positive test results may not be valid in persons who have received blood transfusions or other blood products in the past several months.

Lack of significant increase in IgG antibody level does not exclude the possibility of CMV infection.

IgM responses can vary from patient to patient. A negative result does not preclude the possibility of recent primary CMV infection.

Serum specimens with total IgG concentrations of > or =20 mg/mL may cause interference in the CMV IgM assay.

Results must be used in conjunction with clinical symptoms and patient history.

A specimen taken late after the convalescent stage of infection may not contain detectable levels of IgM antibodies to CMV. Because CMV IgM antibody may persist for many months after primary infection, its detection in a single serum specimen is of limited value in determining the timing when infection occurred. Negative results do not preclude recent infection by CMV.

This test should not be used as a general screen in the absence of clinical symptoms or known exposure.

Epstein-Barr virus (EBV) is known to be a potent B-cell stimulator. Infections with EBV have been suspected to elicit antigen-specific IgM responses in individuals previously sensitized to a variety of non-EBV infectious agents.

CYTOMEGALOVIRUS ANTIBODIES, IgG

<4 AU/mL (negative)

4-5 AU/mL (equivocal)

> or =6 AU/mL (positive)

CYTOMEGALOVIRUS ANTIBODIES, IgM

Negative (reported as positive or negative)

The presence of IgM class antibodies or a convalescent IgG antibody level of >6 AU/mL combined with a ratio of > or =2 in a paired sera (seroconversion) IgG titer indicates recent infection. The presence of only IgG antibodies generally indicates past infection with CMV.

1. Kusne S, Shapiro R, Fung J: Prevention and treatment of cytomegalovirus infection in organ transplant recipients. Transpl Infect Dis 1999;1(3):187-203

2. Rubin RH: Importance of CMV in the transplant population. Transpl Infect Dis 1999;1(1):3-7

3. Lang D, Vornhagen R, Rothe M, et al: Cross-reactivity of Epstein-Barr virus-specific immunoglobulin M antibodies with cytomegalovirus antigens containing glycine homopolymers. Clin Diagn Lab Immunol 2001 July;8(4):747-756