Reference ranges changed effective 12/11/2012.

Reference range for all analytes (Heterophile IgM, VCA IgG, VCA IgM, 
EBNA):
  0.8 AI or less: Negative
  0.9-1.0 AI: Indeterminate
  1.1 AI or greater: Positive

Epstein-Barr virus (EBV) is the etiologic agent of infectious 
mononucleosis. EBV infection can be difficult to diagnose by 
laboratory testing; however, the majority of acute infections can be 
recognized by testing the patient's serum for heterophile antibodies 
(e.g., by the "Monospot" latex agglutination assay), which usually 
appear within the first 3 weeks of illness, but then decline rapidly 
within a few weeks. Heterophile antibodies are found in a very high 
percentage of infants and older children with acute mononucleosis.  
However, heterophile antibodies do not develop in approximately 10% of 
adults.  In cases where EBV is suspected but the heterophile antibody 
is not detected, evaluation of a panel of 4 EBV antibodies can be 
useful:
   Heterophile IgM
   Viral capsid antigen (VCA) IgG
   VCA IgM
   EBV nuclear antibody (EBNA)

Infection with EBV usually occurs early in life, typically as 
infectious mononucleosis. Other disorders due to EBV infection have 
been recognized, including Burkitt's lymphoma and nasopharyngeal 
carcinoma. EBV infection may also cause lymphoproliferative syndromes, 
especially in patients who have undergone renal or bone marrow 
transplantation and in those who have AIDS. 

Presence of VCA IgM antibodies indicates recent primary infection with 
EBV. The presence of VCA IgG antibodies indicates infection sometime 
in the past. Antibodies to EBNA develop 6 to 8 weeks after primary 
infection and are usually detectable for life. Over 90% of the normal 
adult population have IgG class antibodies to VCA and EBNA. Few 
patients who have been infected with EBV will fail to develop 
antibodies to the EBNA (approximately 5%-10%).

EBV serology pattern interpretation is adapted from the findings in J. 
Clin. Microbiol. 47(10): 3204-3210, 2009.  The table below has the 
likely interpretations of the 16 patterns possible from the four 
assays in the EBV panel.  For purposes of classification, 
indeterminate/equivocal results are considered negative in the table 
below.  Results should always be interpreted in conjunction with 
patient history and physical examination.

Heterophile  VCA  VCA  EBNA
    IgM      IgM  IgG  IgG  Interpretation

    Neg      Neg  Neg  Neg  EBV naïve
				
    Neg      Pos  Neg  Neg  Primary acute EBV infection
    Pos      Neg  Neg  Neg  Primary acute EBV infection
    Pos      Pos  Neg  Neg  Primary acute EBV infection
    Neg      Pos  Pos  Neg  Primary acute EBV infection
    Pos      Neg  Pos  Neg  Primary acute EBV infection
    Pos      Pos  Pos  Neg  Primary acute EBV infection
				
    Neg      Pos  Neg  Pos  Recovery from/reactivation of EBV infection
    Neg      Pos  Pos  Pos  Recovery from/reactivation of EBV infection
    Pos      Neg  Pos  Pos  Recovery from/reactivation of EBV infection
    Pos      Pos  Neg  Pos  Recovery from/reactivation of EBV infection
    Pos      Pos  Pos  Pos  Recovery from/reactivation of EBV infection
				
    Neg      Neg  Pos  Neg  Past EBV infection
    Neg      Neg  Pos  Pos  Past EBV infection
				
    Pos      Neg  Neg  Pos  Unknown*
    Neg      Neg  Neg  Pos  Unknown*

* These two patterns are uncommon and have unknown significance.