Serological and clinical findings in patients with serological evidence of reactivated Epstein-Barr virus infection

Abstract

Obel, N., Herier-Madsen, M. & Kangro, H. Serological and clinical findings in patients with serological evidence of reactivated Epstein-Barr virus infection. APMIS 104: 424428, 1996.IgM directed against Epstein-Barr virus (EBV) early antigen (IgM-EA) has been established as an early marker of EBV infection and IgG directed against Epstein-Barr virus nuclear antigen I (IgG-EBNA-1) as a late marker. Simultaneous seropositivity to IgM-EA and IgG-EBNA has therefore been proposed as indicating reactivation of latent EBV infection. We have studied 191 patients with serological evidence of reactivated EBV infection with regard to clinical presentation, antibodies directed against EBV viral capsid antigen (IgM-VCA, IgG-VCA), cytomegalovirus (IgM-CMV). human herpesvirus 6 (IgM-HHV-6), IgM rheumatoid factor (IgM-RF), anti-nuclear or anti-cytoplasmic antibodies (ANA/ACA), and total IgM. The clinical manifestations varied considerably. but a diagnosis was established in 121 of the patients. The diversity of the clinical diagnosis probably reflects common reasons for requesting an EBV serological test rather than clinical manifestations of reactivated EBV infection. Only 5.8% of the patients with "serological EBV reactivation" gave a positive result for IgM-VCA. We conclude that "serological EBV reactivation" does not represent an entity relating to clinical manifestations, but probably reflects a non-specific activation of the immune system.

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

“…Consequently, EBNA-1 IgG, and VCA IgG and IgM may be simultaneously present in patients with primary EBV infection if VCA IgM persist and EBNA-1 IgG have already been produced (a phase that has been variously defined as "recent infection", "primary infection, transient phase or convalescence", "past infection, IgM persisting"), or in those with reactivation and the simultaneous presence of VCA IgM and EBNA-1 IgG [42] . Reactivation is still relatively rare and often short in immunocompetent subjects, and is generally considered of no clinical relevance [113,114] ; however, it can cause serious complications in immunocompromised patients.…”

“…Other antibodies have been found in cases of reactivation. It has been suggested that EBNA IgM may be useful in identifying reactivation [114] . The combination of negative EBNA IgG and positive EBNA IgM, in addition to a high degree of avidity for VCA IgG within 3 mo of an acute infection, should reliably indicate reactivation rather than primary EBV infection [67] .…”

“…Consequently, a search for VCA IgA is considered useful only in the diagnosis and management of patients with nasopharyngeal carcinoma [133][134][135][136] . EA (R) IgG, EA IgM, EA IgA, VCA IgG-3 and the EBNA-1/EBNA-2 ratio have also been used as markers of reactivation in some studies [18,95,114,[137][138][139] but, as many of these antibodies are also present in primary infections, and some even in past infections, the usefulness of a single sample in patients with the simultaneous presence of EBNA-1 IgG, VCA IgG and IgM has yet to be evaluated.…”

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

“…Di conseguenza, tutti e tre i marcatori anti-EBNA-1 IgG, anti-VCA IgG e anti-VCA IgM possono essere contemporaneamente presenti in pazienti con infezione primaria da EBV se gli anti-VCA IgM persistono e gli anti-EBNA-1 IgG sono già stati prodotti (fase che è stata variamente definita come "infezione recente", "fase transitoria" o "tardiva infezione primaria"), o in quelli con riattivazione (31). La riattivazione è comunque relativamente rara e spesso di breve durata nei soggetti immunocompetenti, e generalmente è considerata di nessuna rilevanza clinica (78,83), tuttavia, nei pazienti immunodepressi, può esser causa di gravi complicazioni. Questo pattern sierologico è infrequente (circa il 5% della normale routine di laboratorio) (18), e ulteriori test diagnostici sono necessari per distinguere tra infezione recente e riattivazione (tabella 4).…”

“…Alti livelli sono stati riscontrati anche in pazienti con immunodeficienze, parotiti ricorrenti, sclerosi multiple, carcinoma nasofaringeo, donne in gravidanza e soggetti anziani (2,26,40,52,63,66) per cui generalmente la ricerca degli anti-VCA IgA è considerata utile solo nella diagnosi e gestione dei pazienti con carcinoma nasofaringeo (76,99,108). Anche gli anti-EA-(R) IgG, anti-EA IgM, anti-VCA IgG 3, anti-EA IgA e il rapporto anti-EBNA-1/anti-EBNA-2 (45,67,75,83,115) sono stati utilizzati in alcuni studi come marcatori di riattivazione, ma poichè molti di questi anticorpi (normalmente ricercati solo in laboratori di ricerca o di riferimento) sono presenti anche nell'infezione primaria e alcuni anche nell'infezione pregressa, la loro utilità su singolo campione nei pazienti con simultanea presenza di anti-EBNA-1 IgG, anti-VCA IgG e IgM deve essere ancora valutata. Infine, l'utilizzo di valori di cut-off differenziati proposti dai più recenti CLIA nella determinazione in parallelo di anti-VCA IgG, anti-VCA IgM, anti-VCA IgG e anti-EBNA-1 IgG sembra essere un approccio promettente dal momento che dovrebbe permettere di distinguere le diverse fasi dell'infezione da EBV, soprattutto tra infezione primaria transitoria e pregressa o riattivazione (Tabella 5) (29,73).…”