Diagnosing Epstein-Barr Virus Infection In Chronic Fatigue Syndrome
- A Laymen's Guide by Cort Johnson (Oct 09)
Diagnosing EBV in chronic fatigue syndrome is fraught with controversy. Dr.
Lerner and Dr. Glaser believe that increased levels of antibodies to nonstructural proteins indicate a smoldering
but still problematic EBV infection. Dr. Montoya believes that high IgG levels
are indicative of EBV reactivation (not a first-time infection). The CDC
believes neither of these tests are indicative of an important infection.
Since
the issues revolve around antibodies a short primer on the antibody response and
antibodies is below.
The Antibody Response
Immunoglobulins or antibodies are produced by B-cells when they are
triggered by the presence of antigens. Antigens are anything that
stimulates the immune system but typically they are proteins produced by
pathogens. Not necessarily dangerous in themselves, they are signs of
danger that provoke the immune system to attack.
After a B-cell is
activated it turns into a plasma cell which produces antibodies designed to
attack anything carrying the antigen which activated that B-cell.
Antibodies neutralize pathogens in various ways. Quite large in size they
can stop pathogens from infecting cells simply by attaching themselves to
pathogens and blocking their docking mechanisms. Once they are attached
antibodies also send signals to phagocytes and to the complement system to
attack and remove the invader. Antibodies only attack pathogens found outside of
cells they are unable to attack intracellular pathogens except when they are
dispersed in the bloodstream. Antibody production is a hallmark of the humoral
or Th2 immune response responsible for killing extracellular pathogens.
Antibodies can also neutralize toxins.
Since pathogens typically carry several antigens the immune system
typically produces multiple types of antibodies for each pathogen. Since the
different antigens are often associated with different stages of the pathogens
life cycle, assessing the types of antibodies present can help physicians chart
the course of an infection.
Antibody Tests
The Epstein Barr Virus Pages
- IgM antibodies –
because IgM antibodies usually appear early in an infection and then disappear
they are often a sign of a recent infection or reactivation.
- IgG antibodies – since IgG antibodies to a protein on the viral coat (viral capsid antigen) peak
early in an infection and usually persist for life they usually denote nothing
more than that a person has been exposed to a pathogen. IgG antibodies to an
antigen produced early in EBV’s life cycle (early antigen) are produced
only for 3-6 months and are a good indicator of an active infection. Since about
20% of healthy people carry this antibody for years the IgG early antigen test is, not
definitive. Dr. Montoya believes, however, high IgG levels found in
combination with other clinical signs of chronic fatigue syndrome accurately reflect EBV reactivation.
The success of the B-cell depleting drug Rituximab in post infectious
mononucleosis ME/CFS patients with high IgG titers but no other evidence of
infection ( including serological tests) suggests Dr. Montoya may be correct
(see EBV Part II).
- EBV nuclear antigen (EBNA)
– since EBNA antibodies are found two to four months following the onset of EBV
infection and persist for life they simply indicate that a very recent infection
has not occurred. Assessing the EBNA test is complicated by the different
ways of measuring it; while the standard immunoflorescent test does not
detect EBNA for two to four months some immunoassays can detect within a few
weeks of the initial infection.
There’s obviously some real grey area here and situation is quite complicated.
The CDC posts the following guidelines for assessing EBV tests. The CDC believes
EBV reactivation plays no role in chronic fatigue syndrome.
CDC Guidelines
CDC Guidelines for Assessing EBV Infection
First-Time or Primary Infection - A
first time
EBV infection is indicated if IgM antibody to the viral capsid antigen
is present and antibody to EBV nuclear antigen, or EBNA, is absent. A rising or
high IgG antibody to the viral capsid antigen and negative antibody to EBNA
after at least 4 weeks of illness is also strongly suggestive of primary
infection. In addition, 80% of patients with active EBV infection produce
antibody to early antigen.
Past Infection - If
antibodies to both the viral capsid antigen and EBNA are present, then past
infection (from to 6
months to years earlier) is indicated. Since 95% of adults have been infected
with EBV, most adults will show antibodies to EBV from infection years earlier.
High or elevated antibody levels may be present for years and are not
diagnostic of recent infection.
Reactivation - In the
presence of antibodies to EBNA, an elevation of antibodies to early antigen
suggests reactivation. However, when EBV antibody to the early antigen test is
present, this result does not automatically indicate that a patient's current
medical condition is caused by EBV. A number of healthy people with no
symptoms have antibodies to the EBV early antigen for years after their initial
EBV infection. Many times reactivation occurs subclinically.
Chronic EBV Infection -
Reliable laboratory evidence for continued active EBV
infection is very seldom found in patients who have been ill for more than 4
months. When the illness lasts more than 6 months, other causes of chronic
illness or CFS
should be investigated
The Phoenix Rising website and most of the articles in it are created by a layman. It is not a substitute for a
physician and is for informational uses only.