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Test ID SEBV Epstein-Barr Virus (EBV) Antibody Profile, Serum

Reporting Name

EBV Ab Profile, S

Useful For

Diagnosing infectious mononucleosis when a mononucleosis screening procedure is negative and infectious mononucleosis or a complication of Epstein-Barr virus infection is suspected


This assay is not intended for viral isolation or identification.

Profile Information

Test ID Reporting Name Available Separately Always Performed

Specimen Type


Specimen Required

Collection Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Submission Container/Tube: Plastic vial

Specimen Volume: 1 mL

Collection Instructions: Centrifuge and aliquot serum into a plastic vial.

Specimen Minimum Volume

0.6 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
  Frozen  14 days

Reference Values









Day(s) Performed

Monday through Friday

CPT Code Information


86665 x 2-VCA, IgG and IgM

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SEBV EBV Ab Profile, S 87554-2


Result ID Test Result Name Result LOINC Value
EBVG EBV VCA IgG Ab, S 30339-6
EBVM EBV VCA IgM Ab, S 30340-4
EBNA EBNA Ab, S 22296-8
INT73 Interpretation 69048-7

Clinical Information

Epstein-Barr virus (EBV), a member of the herpesvirus group, is the etiologic agent of infectious mononucleosis. EBV infections are difficult to diagnose in the laboratory since the virus does not grow in standard cell cultures. The majority of infections can be recognized, however, by testing the patient's serum for heterophile antibodies (rapid latex slide agglutination test, eg, MONOS / Infectious Mononucleosis, Rapid Test, Serum), which usually appear within the first 3 weeks of illness but then decline rapidly within a few weeks. The heterophile antibody, however, fails to develop in about 10% of adults, more frequently in children, and almost uniformly in infants with primary EBV infections. Most of these heterophile antibody-negative cases of infectious mononucleosis-like infections are due to cytomegalovirus, but in a series of 43 cases, EBV was the cause in 7. In cases where EBV is suspected but the heterophile antibody is not detected, an evaluation of the EBV-specific antibody profile (eg, EBV viral capsid antigen [VCA] IgM, EBV VCA IgG, and EBV nuclear antigen [EBNA]) may be useful.


Infection with EBV usually occurs early in life. For several weeks to months after acute onset of the infection, it is spread by upper respiratory secretions that contain the virus. Among the clinical disorders due to EBV infection, infectious mononucleosis is the most common. Other disorders due to EBV infection have been recognized for several years, including African-type Burkitt lymphoma and nasopharyngeal carcinoma. EBV infection may also cause lymphoproliferative syndromes, especially in patients who have undergone kidney or bone marrow transplantation and in those who have AIDS.


The test has 3 components: viral capsid antigen (VCA) IgG, VCA IgM, and Epstein-Barr nuclear antigen (EBNA). Presence of VCA IgM antibodies indicates recent primary infection with Epstein-Barr virus (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 detectable for life. Over 90% of the normal adult population has 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%).


Table. Possible Results








No previous exposure




Recent infection




Past infection




See note*




Past infection


*Results indicate infection with EBV at some time (VCA IgG positive). However, the time of the infection cannot be predicted (ie, recent or past) since antibodies to EBNA usually develop after primary infection (recent) or, alternatively, approximately 5% to 10% of patients with EBV never develop antibodies to EBNA (past).


Specimens collected too early during the course of the disease may not contain detectable antibody to Epstein-Barr virus (EBV). Another specimen collected 1 to 2 weeks later may be required.


Test results should be evaluated in relation to patient symptoms, clinical history, and other laboratory findings.


The timing of the appearance of IgG antibodies to viral capsid antigen (VCA) or Epstein-Barr nuclear antigen (EBNA) or IgM antibodies to VCA is subject to variations among individuals and serological assays.


This assay's performance characteristics with immunosuppressed individuals, newborns, cord blood, or matrices other than human serum have not been established.


Assay performance characteristics have not been established for the diagnosis of nasopharyngeal carcinoma, Burkitt lymphoma, and other EBV-associated lymphomas.


Anti-VCA-specific IgG may compete with IgM for binding sites, leading to false-negative results. Rheumatoid factor (RF), in the presence of specific IgG, may contribute to false-positive results. The absorbent in the VCA IgM diluent is intended to neutralize the effects of RF and specific IgG. Studies have shown that the absorbent was able to neutralize up to 98% of the activity in a specimen known to contain 3328 IU/mL of RF activity.


Testing for VCA IgM should not be performed as a screening procedure on the general population. The predictive value of positive or negative results depends on the pretest likelihood of Epstein-Barr-associated disease being present. Testing should only be performed when clinical evidence suggests the diagnosis of this syndrome.

Clinical Reference

1. Knipe DM, Howley PM, Griffin DE, et al, eds. Fields' Virology. 5th ed. Lippincott Williams and Wilkins; 2007

2. Linde A, Falk KI. Epstein-Barr virus. In: Manual of Clinical Microbiology. Barron EJ, Jorgensen JH, Landry ML, eds. 9th ed. ASM Press; 2007:1564-1573

3. Johannsen EC, Kaye KM. Epstein-Barr virus (infectious mononucleosis, Epstein-Barr virus-associated malignant diseases, and other diseases). In: Bennett JE, Dolin R, Blaser MJ, eds. Mandell, Douglas, and Bennett's Principles and Practice of Infectious Diseases. 9th ed. Elsevier; 2020:1872-1890

Method Description

Primary method:

For the detection of viral capsid antigen (VCA)-IgG antibody, EA-D antibody, and Epstein-Barr nuclear antigen (EBNA) antibody, an aliquot of the patient serum, sample diluent, and bead reagent are combined in a reaction vessel. After washing, antihuman-IgG antibody conjugated to phycoerythrin (PE) is added to the beads and incubated. Another wash step removes excess conjugate, and beads are subsequently resuspended in wash buffer. The bead mixture passes through a detector where the identity of each bead is determined by the bead's dye fluorescence. In addition, the amount of antibody captured by the antigen is measured by the fluorescence of the bound PE.


For the detection of VCA-IgM antibody, the patient sample is combined with diluent containing antihuman IgG and bead reagent. The antihuman IgG is incorporated in the mix because any anti-VCA-specific IgG present may compete with the IgM for binding sites, leading to false-negative VCA-IgM results. After a wash cycle, antihuman-IgM antibody conjugated to PE is added. Detection of anti-VCA-specific IgM is performed as described above for the VCA IgG assay.(Package inserts: BioPlex 2200 System EBV IgG and EBV IgM. Bio-Rad Laboratories; IgG 03/2012; IgM 03/2019)


Alternate method for VCA-IgM, as needed:

The ZEUS ELISA EBV-VCA IgM Test System is designed to detect IgM class antibodies to EBV IgM in human sera. Creation of the sensitized wells of the plastic microwell strips occurred using passive adsorption with EBV antigen. The test procedure involves three incubation steps. Test sera are diluted with the Sample Diluent provided. The Sample Diluent contains antihuman IgG that precipitates and removes IgG and rheumatoid factor from the sample leaving IgM free to react with the immobilized antigen. During sample incubation any antigen specific IgM antibody in the sample will bind to the immobilized antigen. The plate is washed to remove unbound antibody and other serum components. Peroxidase Conjugated goat ant-human IgM is added to the wells and the plate is incubated. The Conjugate will react with IgM antibody immobilized on the solid phase. The wells are washed to remove unbound Conjugate.  The microwells containing immobilized peroxidase Conjugate are incubated with peroxidase Substrate Solution. Hydrolysis of the Substrate by peroxidase produces a color change. After a period of time the reaction is stopped and the color intensity of the solution is measured photometrically. The color intensity of the solution depends upon the antibody concentration in the original test sample.(Package inserts: EBV-VCA IgM Test System. Zeus Scientific, Inc.; 12/13/2017)

Report Available

Same day/1 to 2 days

Reject Due To

Gross hemolysis Reject
Gross lipemia Reject
Gross icterus Reject
Heat-inactivated specimen Reject

Method Name

Multiplex Flow Immunoassay (MFI) or Enzyme-Linked Immunosorbent Assay (ELISA)


If not ordering electronically, complete, print, and send 1 of the following forms with the specimen:

-General Request (T239)

-Infectious Disease Serology Test Request (T916)

Test Classification

This test has been cleared, approved, or is exempt by the US Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.