- Complete panel available for the detection of the EBV infection
- Early detection of EBV EBNA IgG in the sera of infected people
- High specificity of the EBNA-1 IgG test in the primary infection
- High specificity and sensitivity of the 3 tests VCA IgG , VCA IgM and EBNA-1 IgG when used together to evaluate the stage of the infection
The EBV EBNA-1 IgG test is a chemiluminescent immunoassay (CLIA), for use on IDS automated analyzers, for quantitative determination of specific IgG class antibodies directed against the Epstein-Barr nuclear antigen (EBNA) in samples of human serum or plasma (K3-EDTA, Sodium Citrate).
This assay is used as a diagnostic aid when assessing infective mononucleosis (IM).
The Epstein Barr virus (EBV) or Human herpesvirus 4 (HHV-4)1 is a virus that resides persistently in the human organism and, may have one of two types of life cycle: a lytic cycle in which active viral replication and production of new virions leads to cell lysis and further propagation, and a latent cycle which corresponds to an apparent state of quiescence in that it is under the strict control of the immune system.
Infection by EBV has a proven aetiological role in infective mononucleosis (IM)2, the typical acute manifestation of which is more frequently found in adolescents and young adults, and in X-linked Lymphoproliferative Syndrome (XLP)3. Infective mononucleosis generally has an incubation period of around 4-6 weeks, while the duration of the acute phase is 2-3 weeks and convalescence may last from around six weeks to six months.
From the epidemiological point of view, 90-95% of the adult population prove to be seropositive and, in particular in industrialised countries, approximately 50% of children are found to be seropositive at 5 years of age.
The main problems for clinical diagnosis of EBV infections are linked to the widely varying possible symptoms. Symptoms associated with EBV infections are similar to those of infections caused by other pathogens or non-infective pathologies, such as: fever for 10-15 days (80-90%), asthenia, angina (80%), cervical and/or axillary adenopathy (80-90%), splenomegaly, hepatomegaly (occasionally with jaundice)…
EBV is ubiquitous in oropharyngeal secretions and contagion occurs via saliva. Contagion may also be caused by blood transfusion or organ transplant.
Following a primary infection by Epstein-Barr virus, an initial phase occurs in which infecting oropharyngeal epithelial cells are produced and are eliminated via the saliva during which they can be transmitted to other individuals.
At the same time, proteins and viral proteic complexes are chronologically expressed.
After the primary infection, the virus persists for the whole life of the individual in a latent non-productive state within B lymphocytes of the memory.
B lymphocytes latently infected by EBV express only the EBNA-1 antigen, corresponding to 10% of the virus’ genome.
On rare occasions, the virus may go back into a new lytic phase, beginning an authentic reactivation of the infection.
When an EBV infection is suspected, serological diagnosis is the prime tool for assessment of the individual’s immune status.
Serological diagnosis of EBV is somewhat complex and has been evolving over time, concentrating on the dosage of IgM and IgG immunoglobulins directed against the various antigens8.
Routine serological investigation measures the antibody response to the viral proteins expressed during the lytic cycle and/or during latency; This investigation consists in dosing IgM immunoglobulins against EA(D) and VCA antigens, and dosing IgG immunoglobulins against EA(D), VCA and EBNA-1
Antibody responses against EA(D), VCA and EBNA-1 antigens show differing clinical significances when used as serological markers:
Early Antigen (EA)
EA(D) are proteins expressed in the early stages of the lytic cycle (p54 and p138). Some weeks after infection IgG against EA(D) appear in 80% of patients. Anti-EA(D) IgG disappear during convalescence
Viral Capsid Antigen (VCA)
VCA are structural proteins that form the viral capsid. In the early stages of infection the first antibodies that appear in most patients’ serum are of the anti-VCA IgM type which reach a peak and then disappear after a few weeks (exceptionally they may persist for weeks or even years). Then anti-VCA IgG antibodies appear and remain indefinitely and stably over time.
Epstein-Barr Nuclear Antigen (EBNA)
The EBNA complex is formed by at least 6 proteins (EBNA 1-6). Some weeks/months after onset, anti EBNA-1 IgG antibodies, considered to be convalescence markers, appear. Anti-EBNA-1 antibodies are therefore generally absent in the acute phase of primary infection and subsequently are related to the individual’s immunological memory.
- Rickinson AB, Kieff E. Epstein-Barr virus. In: Knipe DM, Howley PM, Griffin DE, Martin MA, Lamb RA, editors. Fields virology. Philadelphia: Lippincott Williams and Wilkins;2001, pp 2575-2627
- Steven NM. Infectious mononucleosis. EBV Reports. 1996 – 3 91-95
- Tatsumi E, Purtilo DT. Epstein-Barr virus (EBV) and X-linked lymphoproliferative syndrome (XLP). AIDS Res. 1986 Dec; 2 Suppl 1 : S109-13
- Maeda E, Akahane M, Kiryu S, et al (January 2009). “Spectrum of Epstein-Barr virus related diseases: a pictorial review”. Jpn J Radiol 27 (1): 4-19
- Toussirot E, Roudier J (October 2008). “Epstein-Barr virus in autoimmune diseases”. Best Practice & Research. Clinical Rheumatology 22 (5): 883-96
- Godshall S.E. and J. T. Kirchner. 2000. Infectious mononucleosis. Complexities of a common syndrome. Postgrad. Med.107: 175-179, 183-184,186.
- Lennette E.T. 1995. Epstein-Barr virus (EBV), p. 299-312. In E.H. Lennette , D.A. Lennette E.T. Lennette (ed), Diagnostic procedures for viral, rickettsial, and chlamydial infections, 7th American Public Health Association, Washington, D.C.
- Hess RD. Routine Epstein-Barr virus diagnostics from the laboratory perspective: still challenging after 35 years. J. Clin Microbiol. 2004; 42:3381-3387