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A third-order test in the diagnosis of infectious mononucleosis, especially in situations when initial testing results (heterophile antibody test) are negative and follow-up testing (viral capsid antigen: VCA IgG, VCA IgM, and Epstein-Barr nuclear antigen) yields inconclusive results aiding in the diagnosis of type 2 or type 3 nasopharyngeal carcinoma
Epstein-Barr virus (EBV), a member of the herpesvirus group, is the etiologic agent of infectious mononucleosis. EBV infections are difficult to diagnose in the laboratory since the virus does not grow in standard cell cultures. The majority of infections can be recognized, however, by testing the patient's serum for heterophile antibodies (rapid latex slide agglutination test; eg, MONOS / Infectious Mononucleosis Rapid Test, Serum). Heterophile antibodies usually appear within the first 3 weeks of illness, but then decline rapidly within a few weeks. The heterophile antibody, however, fails to develop in about 10% of adults, more frequently in children, and almost uniformly in infants with primary EBV infections. Most of these heterophile antibody negative cases of infectious mononucleosis-like infections are due to cytomegalovirus, but in 1 series of 43 cases, EBV was the cause in 7. In cases where EBV is suspected but the heterophile antibody is not detected, an evaluation of EBV-specific antibodies (eg, IgM and IgG antibodies to EBV viral capsid antigen: VCA) and antibodies to EBV nuclear antigen (EBNA) may be useful. The EBV EIA tests that detect antibodies to the EBV VCA and early antigen (EA) are more sensitive than heterophile antibody tests.
Infection with EBV usually occurs early in life. For several weeks to months after acute onset of the infection, it is spread by upper respiratory secretions that contain the virus. Among the clinical disorders due to EBV infection, infectious mononucleosis is the most common. Other disorders due to EBV infection include African-type Burkitt lymphoma and nasopharyngeal carcinoma (NPC). EBV infection may also cause lymphoproliferative syndromes, especially in patients with AIDS and in patients who have undergone renal or bone marrow transplantation.
Using immunofluorescent staining techniques, 2 patterns of EA are seen-1) diffuse staining of both cytoplasm and nucleus (early antigen-diffuse: EA-D) and 2) cytoplasmic or early antigen restricted (EA-R). Antibodies responsible for the diffuse staining pattern (EA-D) are seen in infectious mononucleosis and NPC, and are measured in this assay.
The presence of antibody to the early antigen (EA) of Epstein-Barr virus (EBV) indicates that EBV is actively replicating.
Generally, this antibody can only be detected during active EBV infection, such as in patients with infectious mononucleosis. Clinical studies have indicated that patients who have chronic active or reactivated EBV infection commonly have elevated levels of IgG-class antibodies to the EA of EBV.
IgG antibody specific for the diffuse early antigen of EBV is often found in patients with nasopharyngeal carcinoma (NPC). Of patients with type 2 or 3 NPC (World Health Organization classification), 94% and 83% respectively, have positive-antibody responses to EA. Only 35% of patients with type 1 NPC have a positive response. The specificity of the test is such that 82% to 91% of healthy blood donor controls and patients who do not have NPC have negative responses (9%-18% false-positives). Although this level of specificity is useful for diagnostic purposes, the false-positive rate indicates that the test is not useful for NPC screening.
This test detects the diffuse components of early antigen only.
1. Fields BN, Knipe DM: Epstein-Barr virus. In Fields Virology. Fourth edition. Edited by BN Fields, DM Knipe, PM Howley. Philadelphia, Lippincott Williams and Wilkins, 2001
2. Lennette ET: Epstein-Barr virus. In Manual of Clinical Microbiology. Sixth edition. Edited by PR Murray, EJ Baron, MA Pfaller, et al. Washington, DC, ASM Press, 1995, pp 905-910