Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (1346 page)

   Limitations

   Currently, there is no international standard available for calibration of this assay. Therefore, caution should be taken when interpreting results obtained by different laboratories or assay methodologies. PCR inhibitors in the patient specimen may lead to underestimation of viral quantitation or in rare cases, false-negative results. Proper storage and timely separation serum or plasma are necessary for obtaining reliable results. EBV DNA released from the intracellular compartment may cause false-positive EBV results in plasma or serum. False-negative results can be obtained due to nuclease activities.

   
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/InVitroDiagnostics/ucm330711.htm

EPSTEIN-BARR VIRUS (EBV) SEROLOGY SCREEN ANTIBODY PROFILE

   Definition

   EBV is the etiologic agent of infectious mononucleosis (IM) and is a widely disseminated herpesvirus that is spread by intimate contact between susceptible persons and EBV shedders. EBV spreads primarily via passage of saliva but is not a particularly contagious disease. The virus can persist in the oropharynx of patients with IM for up to 18 months following clinical recovery. EBV has also been isolated in both cervical epithelial cells and in male seminal fluid, suggesting that transmission may also occur sexually. This test comprises four serologic markers: EBV-NA (nuclear antigen IgG); EBV-VCA (viral capsid antigen) IgG and IgM; infectious mononucleosis antibody; and EBV-EA IgG (early antigen IgG).

   
Normal range:
Negative.

   
Tests for EBV:

   
IgG-VCA:
Indicates past infection and immunity. May be present early in illness, usually before clinical symptoms are present. Detected at onset in 100% of cases; only 20% show a fourfold increase in titer after visiting a physician. Decreases during convalescence but detectable for many years after illness; therefore, not helpful in establishing diagnosis of IM.

   
IgM-VCA:
Detected at onset in 100% of cases; high titers present in serum 1–6 weeks after onset of illness, starts to fall by 3rd week and usually disappear in 1–6 months. Sera are often taken too late to be detected. It is almost always present in active EBV infection and, thus, most sensitive and specific to confirm acute IM. May be positive in other herpes virus infections (especially CMV); therefore, confirmation with IgG and EBV-NA assays is recommended.

   
Early antigen:
IgG antibodies to early antigen are present at the onset of clinical illness. There are two subsets of EA IgG: anti-D and anti-R. The presence of anti-D antibodies is consistent with recent infection, since titers disappear after recovery; however, their absence does not exclude acute illness because the antibodies are not expressed in a significant number of patients. Anti-R antibodies are only occasionally present in IM.

   Early antigen anti-D titers rise later (3–4 weeks after onset; is transient) in course of IM than AB-VCA and disappear with recovery; combined with IgG-VCA suggests recent EBV infection; only found in 70% of patients with IM due to EBV. High titers are found in nasopharyngeal carcinoma due to EBV. Early antigen anti-R antibodies occur rarely in primary EBV infection, 2 weeks to months after onset, and may persist for a year; more often in atypical or protracted cases. No clinical significance; high titers are found in chronic active EBV infection or Burkitt lymphoma.