Evidence-Based Approach for Interpretation of Epstein-Barr Virus Serological Patterns

Abstract

Diagnosis of Epstein-Barr virus (EBV) infection is based on clinical symptoms and serological markers, including the following: immunoglobulin G (IgG)and IgM antibodies to the viral capsid antigen (VCA), heterophile antibodies, and IgG antibodies to the EBV early antigen-diffuse (EA-D) and nuclear antigen (EBNA-1). The use of all five markers results in 32 possible serological patterns. As a result, interpretation of EBV serologies remains a challenge. The purpose of this study was to use a large population of patients to develop evidence-based tools for interpreting EBV results. This study utilized 1,846 serum specimens sent to the laboratory for physician-ordered EBV testing. Chart review was performed for more than 800 patients, and diagnoses were assigned based on physician-ordered testing, clinical presentation, and patient history. Testing for all five EBV antibodies was performed separately on all serum samples using the Bio-Rad BioPlex 2200 system. Presumed EBV diagnosis (based on previous publications) was compared to EBV diagnosis based on a medical record review for each serological pattern. Interestingly, of the 32 possible serological patterns, only 12 occurred in >10 patients. The remaining 20 patterns were uninterpretable because they occurred with such infrequency. Two easy-to-use tables were created to interpret EBV serological patterns based on whether three (EBV VCA IgG, IgM, and heterophile) or five markers are utilized. The use of these two tables allows for interpretation of >95% of BioPlex serological results. This is the first evidence-based study of its kind for EBV serology.

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

“…The use of heterophile antibodies is controversial because some studies have shown that they are very sensitive (94% of infected patients with transient infection) [124] , whereas others have found very few cases of simultaneous positivity for EBNA-1 IgG, VCA IgG, VCA IgM and heterophile antibodies [109] . The use of molecular biology seems to be a rather delicate question.…”

“…However, as high titers can be found during EBV reactivation [26] , as well as in 20%-30% of healthy subjects with past infection [2,25] and in patients with nasopharyngeal carcinoma [27] , the diagnostic use of these antibodies is still being debated. In general, a search for EA (D) IgG alone does not identify the stage of disease [43,109] , but combining these antibodies with other parameters can be useful in laboratory diagnoses [110] because it has been found that only 12% of the patients with isolated VCA IgG and past infection are EA (D) IgG positive, as against 90% of subjects with isolated VCA IgG and acute infection [111] .…”

Avaliação diagnóstica das infecções por vírus Epstein-Barr, parvovírus B19 e vírus linfotrópico de células T humanas em pacientes portadores de lúpus eritematoso sistêmico em hospital de referência do Estado do Pará, Brasil

“…Para infecções primárias agudas, nota-se uma produção de IgM mais eficiente em relação aos períodos de reativação do EBV 54 . Como as infecções primárias pelo vírus ocorrem, em sua grande maioria, em crianças e adultos jovens 18 , isso explicaria a associação dessa resposta humoral aguda com pacientes menos senis.…”

EBV infection in immunocompetent patient: problems and solutions in serological diagnosis

“…Utilizzando i test per l'avidità delle IgG è importante conoscere da quanto tempo dall'esordio dei sintomi il prelievo è stato effettuato per poter valutare correttamente i risultati ottenuti in relazione al tempo di maturazione dei vari anticorpi. Controverso è l'uso della ricerca degli anticorpi eterofili in quanto mentre in alcuni studi è stato visto essere molto sensibile in questi pazienti (il 94% dei pazienti con infezione recente aveva anticorpi eterofili) (50), in altri studi un pattern con contemporanea positività per anti-EBNA-1 IgG, anti-VCA IgG, anti-VCA IgM e anticorpi eterofili è stato trovato in pochissimi casi (59). L'uso della biologia molecolare sembra essere una questione abbastanza delicata.…”