In addition to its well-known role in infectious mononucleosis (IM), Epstein-Barr virus (EBV) is implicated in several malignancies, including Burkitt's lymphoma and nasopharyngeal carcinoma. Fortunately, increasing demand for viral testing has made sophisticated blood tests for EBV more easily available, and these tests are now being routinely performed at MuirLab.
The traditional Monospot test is still helpful for evaluating patients with acute "mononucleosis syndrome." However, 10-20% of adults (and even more children) with acute IM may have negative Monospot results at the time of presentation, and conversion to a positive Monospot may take months.
Confirmation of EBV infection in these Monospot-negative patients can be obtained with additional testing. Serum antibodies to viral capsid antigen (VCA) are present in most (but not all) IM patients at the time of clinical presentation. As with many other infections, IgM antibodies disappear in a few months while IgG antibodies persist indefinitely. An acute infection can be demonstrated either by the presence of IgM antibody or by a rising level of IgG antibody upon repeat testing.
Another useful antibody is EBNA, directed against Epstein-Barr nuclear antigen. This antibody increases gradually during convalescence from IM, and persists for life. Thus, the appearance of this antibody in a patient who was previously VCA positive but EBNA negative indicates a recent infection.
Antibodies to "early antigens" (EA-R and EA-D), are found transiently in most patients with an acute EBV infection. Persistently elevated antibody titers to EA and EBNA together may suggest reactivation or persistently active EBV infection.
In order to facilitate EBV diagnosis, MuirLab offers a convenient EBV antibody panel, which includes four tests: VCA IgM, VCA IgG, EBNA, and EB Early Antigen D. Since the serologic response to early EBV infection can change over a period of several weeks, repeat testing is recommended if the initial panel results are not clear-cut or do not correlate with the patient's clinical picture.
As an example, consider the testing results for a 15 year old child who recently presented with cervical adenopathy, hepatosplenomegaly, fever, and malaise. After a Monospot test was negative, the patient's pediatrician ordered the EBV panel. All four tests in the panel were negative, and the patient was referred to a specialist. That physician decided to order tests for viral hepatitis and CMV, which were negative. At the same time, the EBV panel was repeated. By then, four weeks had elapsed, and three out of the four EBV tests had converted to positive (only the EBNA was still negative; this would be expected to turn permanently positive at some point during convalescence).
For most patients, the four-test EBV panel (repeated in several weeks if necessary) will provide the necessary diagnostic information. For special situations, PCR testing of actual viral DNA can be performed on serum or plasma, or in-situ hybridization can be performed on tissue biopsies (these tests are sent to reference laboratories).
The commonly ordered EBV panel includes only IgG and IgM antibodies. If EBV-related nasopharyngeal carcinoma is a clinical concern (for example, in patients from demographic groups at high risk), serologic testing should include IgA antibodies to VCA (tested at our reference laboratory), because these are more specific for that malignancy than are the IgG antibodies.
It has been estimated that EBV will infect 90% of the world's people over their lifetimes. The multiple roles of this virus will continue to be the focus of much research. With the four-test EBV panel now available, at least the diagnostic evaluation of MuirLab patients is now more convenient than ever before.