Differentiation of primary from secondary anti-EBNA-1-negative cases by determination of avidity of VCA-IgG.

Background: Serological techniques are used to determine Epstein Barr virus (EBV) etiology of a constellation of signs or symptoms related to lymphadenopathy, fever, respiratory tract infection, mononucleosis, hepatitis, thrombocytopenia or neurological disorder. Anti-Epstein Barr Nuclear antigen (EBNA)-1 is regularly negative during the first 3-4 weeks after the onset of clinical symptoms indicating acute EBV infection (primary anti-EBNA-1-negative). It may, however, also be negative in immunocompromised convalescent individuals (secondary anti-EBNA-1-negative) such as tumor patients, HIV-positive patients and transplant recipients.

Objective: The aim of this study was to determine the frequency of secondary anti-EBNA-1-negative cases and to find a way to distinguish them from primary anti-EBNA-1-negative cases using anticomplementary immunofluorescence (ACIF) and enzyme immunoassay (EIA).

Methods: All sera sent to our institute for EBV serology during one year were routinely tested for Viral Capsid antibody (VCA)-IgM, VCA-IgG and anti-EBNA-1.

Results: VCA-IgG-positive/anti-EBNA-1-negative cases (13.5% of total VCA-IgG-positive) comprised 55% primary and 45% secondary anti-EBNA-1-negative cases. Detection of secondary anti-EBNA-1-negative cases was independent of the method used, i.e., ACIF or EIA. VCA-IgG retained its high avidity in secondary anti-EBNA-1-negative cases, whereas primary anti-EBNA-1-negative cases taken during the early phase of acute infection showed low avidity of VCA-IgG.

Conclusions: Determination of the avidity of VCA-IgG routinely and in concert with standard serodiagnosis (VCA-IgG, VCA-IgM, anti-EBNA-1) can enable the differentiation of primary and secondary anti-EBNA-1-negative cases.