EBV and Cellular Immune Deficiencies

created 3/7/00
date of last edit: 05/16/08

EBV Serology

 This information is for individuals who may be involved in research on EBV or those using serology test results to monitor patients with EBV infection. The information that I am providing here is based on observations that I have made over 15 years of being involved with EBV serology testing in a major clinical reference laboratory in Cambridge, Massachusetts.

There four serology tests used to detect antibodies to EBV. The four are:

  • EBV viral capsid antigen antibody IgM (EBV IgM)

  • EBV viral capsid antigen antibody IgG (EBV IgG)

  • EBV early antigen antibody (EBV EA)

  • EBV nuclear antigen antibody (EBNA)

A simplified EBV serology chronology is as follows. EBV IgM when present in the blood indicates a primary current infection with this virus. IgM antibody is quickly followed by the appearance of EBV IgG antibody. Shortly after EBV IgG is detected EBV early antigen antibody appears. EBV IgM and EBV EA will eventually disappear. Finally within 30 to 60 days EBNA antibody appears. EBV IgG and EBNA will remain for life.

Once infected with EBV one remains infected for lifetime. For the most part the viral infection becomes dormant and no further illness is evident . See EBV and Cellular Immune Deficiencies.

However, if viral activity recurs it can be detected with the use of serology tests. At least this was possible with the methodologies available in clinical laboratories when serology tests for EBV were first introduced in the 1980's.

The methodology that became available in the 1980's is called indirect immunofluorescence or IFA. The methodology of choice today is the enzyme-linked immunoassay or EIA. I am not going to discuss the differences in the methodologies. I will say that the reason to switch was predicated on a number of reasons. EIA is less expensive and quicker than IFA. EIA also  does not require the degree of technical skill that IFA requires. As the requests for EBV serology testing increased, it became necessary to reduce costs and increase turnaround time.

All major laboratories have switched to EIA for EBV IgG, EBV IgM and EBNA serology testing. EBV EA is still performed by IFA although this too may soon be replaced by EIA.

When a methodology is changed there will always be discrepancies detected between the old and the new methodologies when comparing patient results. This was also noticed when IFA testing was being switched to EIA testing. However, as the switchover to EIA from IFA progressed what may have been overlooked was the increasing number of discrepancies within the EBV serology panel consisting of EBV IgG, EBV IgM, EBV EA, and EBNA.

During the years that I worked  with IFA only for EBV serology I do not recall any disagreements within a patient panel. If the EBNA was positive then the EBV IgG was positive. If the EBV EA was positive then the IgG (and possibly IgM) was positive. However, with the introduction of EIA the following disagreements have been noted:

  • EBNA present with absence of EBV IgG

  • EBV EA present with absence of EBV IgG

  • EBV IgM is not necessarily present when one would expect it to be when using other clinical signs to detect primary EBV infection

When doing research one may want to employ IFA. If not it may be possible to use EIA and to use IFA as a confirmation test when discrepancies within the EBV panel are noted. When doing research any negative or equivocal EBV IgG result determined using EIA should be confirmed with IFA.

General comments on titers

EBV IgG titers generally run between 1:320 and 1:1280 in convalescent patients and will remain so indefinitely. If viral reactivation occurs these titers will increase approximately twofold. EIA indices are unpredictable.

EBV EA titers are generally absent during convalescence or will titer from 1:10 to 1:80. Anything above 1:80 may indicate current viral activity.

EBNA is generally reported as positive or negative. Once EBNA becomes positive it should remain so for one's lifetime.