Seroepidemiology of EBV and interpretation of the “isolated VCA IgG” pattern

Abstract

The presence of VCA IgG in the absence of VCA IgM and EBNA-1 IgG antibodies makes classifying EBV infection more difficult as this serological picture can be seen in the case of past infection with EBNA-1 IgG loss or non-appearance, or acute infections with the early disappearance or delayed onset of VCA IgM. The aim of this study was to assess the prevalence of this pattern in 2,422 outpatients with suspected EBV infection examined in 2005-2006, and to interpret its significance by means of immunoblotting. One hundred and seventy-seven (7.3%) of the patients were VCA IgG-positive, VCA IgM-negative and EBNA-1 IgG-negative, 15 of whom (8.5%) presented with heterophile antibodies. Analysis by age class showed that the prevalence of isolated VCA IgG ranged from 4.5% in the subjects aged 1-10 years to 9% in those aged >60 years. Immunoblotting allowed 18.9% of the cases to be classified as acute and 81.1% as past infections, the latter being observed in about 37% of the patients aged less than 10 years and in 100% of those aged >30 years. Therefore, in our case series, the presence of isolated VCA IgG was associated usually with past infection, particularly among adults. In children aged less than 10 years, it was associated mainly with acute infection but as past infection may be present in about one-third of such children, this possibility should not be overlooked.

Serological diagnosis of Epstein-Barr virus infection: Problems and solutions

“…Consequently, isolated VCA IgG may be found in cases of past infection with the loss or disappearance of EBNA-1 IgG, as well as in cases of acute infection with the delayed or early disappearance of VCA IgM. This pattern can be found in approximately 7% of cases in routine laboratory practice and in about 8% of all subjects with at least one marker of EBV infection; it also tends to become more frequent with advancing age [107] . Such cases require further diagnostic investigations (Table 5), including immunoblotting for IgG, avidity tests for VCA IgG, searches for viral genome, or heterophile antibodies or EA (D) IgG [43] , or a repetition of the test after about 30 d in order to identify any change in the antibody profile.…”

“…Such cases require further diagnostic investigations (Table 5), including immunoblotting for IgG, avidity tests for VCA IgG, searches for viral genome, or heterophile antibodies or EA (D) IgG [43] , or a repetition of the test after about 30 d in order to identify any change in the antibody profile. However, this last option inevitably delays the diagnosis until the second sample is collected, and physicians tend to avoid it if the symptoms improve over time, especially in the case of children, they may find it traumatic, which means the second sampling usually involves only a small number of patients [107] . Immunoblottting for IgG allows the interpretation of cases with isolated VCA IgG [23] .…”

“…Immunoblotting can therefore distinguish cases with the loss or nonappearance of EBNA-1 IgG, which however develop an anti-p18 IgG response, from those with primary EBNA-1 IgG negativity (acute infection) [23,108] . Using this method to examine cases of isolated VCA IgG, about 20% was identified as acute infections and 80% as past infections [107] . A VCA IgG avidity test can also be used to distinguish acute and past infection [64,67] , which are respectively characterized by low and high levels of avidity; studies of patients with isolated VCA IgG have found low levels in about half of the cases, and high levels in the remaining half [75,86] .…”

“…A search for heterophile antibodies may be useful in patients with isolated VCA IgG if the result is positive, although there have been reports of their presence for 6-12 mo [28,35,48] . About 60% of patients with acute infection and isolated VCA IgG present heterophile antibodies, as against none of those with past infections [107] . However, nothing can be said in the absence of heterophile antibodies, especially in children aged less than 5 years, and other tests must be used.…”

“…This serological pattern is uncommon (approximately 5% in normal routine laboratory practice) [107] , and further diagnostic tests are needed to distinguish transient infection and reactivation (Table 6). First of all, it is important to verify the specificity of VCA IgM because there may be false positive results [115][116][117] during the course of infection with other pathogens, such as HCMV, parvovirus B19, Toxoplasma gondii, hepatitis A or HIV [118][119][120][121][122][123][124] .…”