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Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that affects more than 95% of the world's population and is the causative agent of infectious mononucleosis (IM). It is also associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and lymphoproliferative disorders occurring in primary and acquired immunodeficiency disorders. The most common screening test for IM is the Monospot, which detects IgM heterophile antibodies. The Monospot test usually becomes positive within the first three weeks of illness. Approximately 10-20% of adults and over 50% of children under four have a negative heterophile test. For these patients, and patients with unusual clinical presentations, the more sensitive and specific EBV antibody panel may be appropriate. This panel includes: IgG antibody to viral capsid antigen (IgG-VCA), IgM antibody to viral capsid antigen (IgM-VCA), and IgG antibody to Epstein-Barr nuclear antigen (IgG-EBNA). Most patients already have detectable levels of EBV specific antibodies when they become symptomatic because of the lengthy incubation period of 5 to 7 weeks following exposure to EBV. IgM-VCA becomes positive within 2 weeks of exposure and disappears within 2-6 months in adults and even sooner in young children. IgG VCA antibody develops later and persists throughout life. EBNA antibodies tend to appear even later, 6 to 12 weeks after initial symptoms, and persist indefinitely. EBV Antibody panel results are interpreted as follows:
Detection of VCA IgM usually confirms acute EBV infection, because this antibody disappears by 3 months after the illness begins. At least 90% of adults have previously been infected with EBV and have positive IgG-VCA and IgG-EBNA tests, since these antibodies remain elevated throughout life. IgG-VCA and EBNA are markers of previous EBV infection and do not indicate chronic active EBV infection. Reactivation of latent EBV can occur in immunodeficient or immunosuppressed patients. IgM-VCA antibodies may be transiently positive concurrently with rapidly rising high titers of IgG-VCA. Few patients (approximately 3%) who have been infected with EBV will fail to develop EBNA antibodies. Positive VCA IgM results are not always due to acute infection. Low levels of VCA IgM have been reported in EBV reactivation. Low level VCA IgM may also represent crossover of VCA IgG. Although VCA IgM should be undetectable within 8 weeks after acute infection, it has been seen to persist for up to a year or more. False positive IgM levels have been reported due to cross-reactivity with cytomegalovirus (CMV), toxoplasma and herpes simplex antibodies. Rheumatoid factors may also cause false positive IgM results. An increased incidence of positive IgM (12%) has been reported in patients over 60 years of age. Several reports have suggested that patients with chronic fatigue syndrome or chronic mononucleosis have EBV antibody panels consistent with reactivated EBV infections. However, it has been convincingly demonstrated that EBV serology is not helpful in the clinical evaluation of patients with chronic fatigue. Specimen requirement is one SST tube of blood. |
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