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Explanation of Raised EBV Antibodies in the Blood Serum

Written by Jan Modric, February 10th, 2009

Introduction

The aim of this article is to help to explain results of tests of EBV (Epstein-Barr virus) antibodies levels in the  blood .

The main reason for elevated EBV antibodies in the blood is infectious mononucleosis (IM). 95% of us were probably infected with EBV at some point in life, but only some of us had notable symptoms of IM (1).

ACUTE Infectious Mononucleosis

Adolescents and young adults with IM typically develop fever, sore throat, and enlarged (palpable) lymph nodes in the neck, armpits and groin 30-50 days after infection. Infants, and children under 10 years of age often don’t show any symptoms of IM after infection with EBV. Severity of infection tends to increase with age. Old people often develop hepatitis (without jaundice), but not sore throat and enlarged nodes. Symptoms usually lasts for 1-2 months (seldom over 4 months) and then in most cases resolve without any consequences. Blood serum shows:

  • Normal to moderately elevated WBC (white blood cells)
  • Increased % of lymphocytes (a type of white blood cells) among which there are at least 10% of atypical lymphocytes

Antibodies that are raised in blood serum in ACUTE EBV infection:

  • VCA-IgM (IgM antibodies to EBV Viral Capsid Antigen) appear first, disappear in 4-6 weeks, but may persist for about 1 year.
  • VCA-IgG (IgG antibodies) appear within a week of infection, then it persists for life. Rising VCA-IgG levels tends to indicate an active EBV infection, while falling concentrations tend to indicate a recent EBV infection that is resolving.
  • EA-D-IgG (IgG antibodies to EBV Early Antigen Diffuse) are positive in about a week, usually gone in 2 weeks, persists in 20% of people.
  • Heterophile antibodies (“monospot” and Paul-Bunnell test (2)) appear after 7-14 days (meaning that on the beginning they are negative), and decline after 4th week, and may sometimes persist for 1 year. These antibodies, together with atypical lymphocytes and symptoms, are considered as confirmation of infectious mononucleosis. Heterophile antibodies do not appear in about 10% of adults in about 50% of children. Heterophile test also have some false positive and negative results though. If a person has negative mono spot test, but symptoms consistent with IM, specific antibody tests (see above) are needed to confirm EBV infection. Heterophile-negative infectious mononucleosis may be also caused by HIV, HHV-6, toxoplasmosis, CMV, rubella, or anicteric viral hepatitis.
  • VCA-IgA = IgA antibodies to the EBV Viral Capsid Antigen
  • EA-R-IgG = IgG antibodies to the EBV Early Antigen Restricted

Explanation. Presence of VCA-IgM and absence of EBNA-IgG antibodies speak for acute EBV infection.

Someone who was infected at any point in the life, having symptoms or not, will not develop symptoms of IM after next exposure to EBV.

LATENT EBV Infection (Indicates PAST Infection)

After acute EBV infection, EBV virus remains dormant (sleeps) in epithelial cells of the throat, in nervous tissue, and in B lymphocytes in the blood. Virus in B lymphocytes doesn’t overgrow, since it is controlled by T lymphocytes that destroy infected B lymphocytes on the regular basis. This latent phase is harmless, there’s no symptoms, and it persists for life. This is not a disease and no treatment is needed. The major hallmark of this phase is appearance of EBNA-IgG antibodies.

Antibodies that are raised in blood serum in LATENT EBV infection (they indicate PAST infection):

  • EBNA-IgG= IgG antibodies against EBV Nuclear Antigen appear 2 to 4 months (sometimes in first weeks) after onset of symptoms, and persists for life
  • VCA-IgG- IgG antibodies against EBV Virus Capsid Antigen appears after the first week of onset of symptoms and persists for life
  • (EA-D-IgG persists in 20% of people with past EBV infection)

Explanation. In latent infection, IgG antibodies are present, and IgM antibodies are absent. Latent infection speaks for PAST infection that occurred at least 4-6 months before testing.

REACTIVATED EBV Infection

In a person who was infected once in the life (having symptoms or not), raise of EBV antibodies in blood serum may be triggered by stress or disease. Typical symptoms of IM may appear or not.

Antibodies that are raised in REACTIVATED EBV infection:

  • VCA-IgM
  • EA-IgM
  • VCA-IgG
  • EA-D-IgG = antibodies against EBV Early Antigen – Diffuse. Antibodies against EA are present in the blood serum due to EBV virus that was dormant in the body and was reactivated, OR due to their persistence after acute EBV infection.
  • EBNA-IgG

Explanation. Both IgM antibodies that speak for active infection, and EBNA-IgG that speak for past infection, are present.

CHRONIC Active Infectious Mononucleosis

In persons with symptoms lasting over 6 months, specific EBV antibodies that would confirm active chronic EBV infection are rarely found in the blood serum. These are possible reasons:

  • Symptoms are of psychic nature
  • Symptoms are caused by other causes like cytomegalovirus (CMV), toxoplasmosis, viral hepatitis, etc.

EBV antibodies in blood serum in CHRONIC EBV infection:

  • VCA-IgG
  • EBNA-IgG
  • EA-D-IgG
  • EA-R-IgG

Explanation. Absence of Ig-M antibodies, and persistence of EA-D and EA-R antibodies for over the year speaks for chronic EBV infection.

Criteria for Different Types of EBV Infection

In below table there are possible combinations of EBV antibodies tests results in different types of EBV infection (15):

  • CURRENT ACUTE EBV infection:
    • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG positive, EBNA-IgG negative} or
    • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG negative, EBNA-IgG negative} or
    • {VCA-IgM and EA-IgM negative, VCA-IgG and EA-IgG positive, EBNA-IgG negative}
  • PREVIOUS EBV infection:
    • {VCA-IgM and EA-IgM negative, VCA-IgG, EA-IgG, and EBNA-IgG positive} or
    • {VCA-IgM and EA-IgM negative , VCA-IgG and EA-IgG negative, EBNA-IgG positive}
  • REACTIVATION of EBV infection:
    • {VCA-IgM and EA-IgM positive, VCA-IgG, EA-IgG, and EBNA-IgG positive} or
    • {VCA-IgM and EA-IgM positive, VCA-IgG and EA-IgG negative, EBNA-IgG positive}
  • CHRONIC EBV infection:
    • EBNA-IgG and VCA-IgG positive, EA-D-IgG possibly positive, all IgM antibodies negative

CONDITIONS With Elevated EBV Antibodies

1. ACUTE INFECTIOUS MONONUCLEOSIS. If you have VCA-IgG, EA-IgG, and all igM positive, and EBNA-IgG negative, and if you’re child or young adult with symptoms (sore throat, fever, enlarged lymph nodes), you probably have acute infectious mononucleosis. As mentioned, symptoms may be absent.

2. INFECTION WITH EBV IN THE PAST (LATENT INFECTION). If EBNA-IgG,VCA-IgG, and maybe also EA-IgG are positive (with levels as expected), and all IgM antibodies are negative, this ONLY means you’ve been infected with EBV virus at some point of your live, so this is an evidence of PAST infection. This result by itself is not a sign of any disease; most of adults in western world will have this result.

But if above antibodies are unusually high (“off the chart”), it is possible that they were triggered by one of disorders from below list (including stress).

3. REACTIVATION OF EBV INFECTION. If you have positive EBNA-IgG, and positive VCA-IgM, this is a sign of reactivation of your past infection, and you may experience some or all (or none) symptoms of acute IM. This reactivation may, again, be due to stress or a disease from below list, so you may also have symptoms of this disease.

4. CHRONIC EBV INFECTION. If you had confirmed acute infectious mononucleosis, and your symptoms persists for over 6 months, and if you have positive VCA-IgG, EBNA-IgG, EA-R, and EA-D antibodies, then it’s possible you have chronic infectious mononucleosis. Again, this type is rarely confirmed with lab tests, so it’s likely your symptoms are of psychic nature, represent complications of EBV infection, or are from some disease listed below.

5. LIST (incomplete) OF DISORDERS THAT MAY BE ASSOCIATED WITH INCREASED LEVEL OF EBV ANTIBODIES IN THE BLOOD SERUM. It is not always clear, if EBV virus has caused these disorders, or elevated EBV antibodies are result of these disorders.

References:

  1. Phases of EBV infection (cdc.gov)
  2. Mono spot test (heterophile antibodies) (drugs.com)
  3. Phases of EBV infection with accent on latent phase (detailed) (uq.edu.au)
  4. Some disorders related to EBV  (newworldencyclopedia.org)
  5. Multiple sclerosis asociated with EA and VCA antibodies (direct-ms.org)
  6. Autoimmune hepatitis/thyroiditis, polymiositis, Kawasaki – EBV antobodies (medscape.com)
  7. Antibodies in multiple sclerosis: VCA-IgG & EBNA (mult-sclerosis.org)
  8. EBV antibodies (labtestsonline.org)
  9. EBV and other diseases (smokershistory.com)
  10. EBV antibodies in CFS (palpath.com)
  11. PCBs and elevated EA IgG (safe2use.com)
  12. EBV causes interstitial lung disease (smokershistory.com)
  13. Gastric carcinoma (smokershistory.com)
  14. Lymphoepithelioma like lung cancer (smokershistory.com)
  15. EBV antibody levels in various phases of EBV infection explained (pubmedcentral.nih.gov)

Useful links:

 

This article is for educational purpose, and can not be a substitute for a doctor’s advice.

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This entry was posted on Tuesday, February 10th, 2009 at 10:00 am and is filed under Infectious Diseases, Uncategorized. You can follow any responses to this entry through the RSS 2.0 feed. You can leave a response, or trackback from your own site.

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