A high incidence of serum IgG antibodies to the Epstein-Barr virus replication activator protein in nasopharyngeal carcinoma

Abstract

The BamHI Z EBV replication activator (ZEBRA) protein is involved in the switch from latency to productive cycle of Epstein-Barr virus. A recombinant ZEBRA protein was synthesized and assessed in enzyme-linked immunosorbent assay (ELISA) for serum IgG response in nasopharyngeal carcinoma (NPC) patients. In 100 NPC serum samples that were positive for IgA to the EBV viral capsid antigen (VCA), 75% had IgG anti-ZEBRA antibodies. In contrast, only 3/83 (3.6%) serum samples from healthy donors and 2/50 (4%) from other cancers were positive for IgG to ZEBRA. Interestingly, in a selected group of 100 NPC sera negative for IgA to VCA, 25% contained IgG anti-ZEBRA antibodies. This suggests that the ELISA for IgG anti-ZEBRA may also identify earlier cases of NPC not detected by the conventional immunofluorescence test for IgA to VCA.

The disease associations of the antibody response against the Epstein--Barr virus transactivator protein ZEBRA can be separated into different epitopes

“…In the case of NPC, early detection is critical for the outcome and screening for NPC using EBV serology (IgA/VCA) has been thoroughly evaluated (Zeng et al, 1983(Zeng et al, , 1985. Both IgG anti-ZEBRA (Mathew et al, 1994) and IgA anti-EBNA-1 (Cheng et al, 1993) can be used to complement the IgA/VCA test, since they both have a high predictive value for NPC and since a substantial proportion of IgA/VCA-negative NPC cases are positive for IgG/ZEBRA or IgA/EBNA-1. However, both IgA/ VCA (Marklund et al, 1986), IgG/ZEBRA (Joab et al, 1991 a) and IgA/EBNA-1 (unpublished observation) are regularly positive in IM patients.…”

“…Antibodies against ZEBRA have been detected among 75-87% of NPC patients *Author for correspondence. Fax +46 8 326702. e-mail Joakim.Dillner @ mtc.ki.se (Joab et al, 1991 a;Mathew et al, 1994), among 85 % of IM patients and among 32% of sera from human immunodeficiency virus (HIV)-infected subjects (Joab et al, 1991b). In contrast, only 2-4% of healthy EBVseropositive donors have ZEBRA antibodies (Joab et al, 1991a, b;Mathew et al, 1994), implying that the presence of antibodies to ZEBRA is a serological marker of EBV-associated disease rather than of EBV infection.…”

Improved Accuracy of Detection of Nasopharyngeal Carcinoma by Combined Application of Circulating Epstein–Barr Virus DNA and Anti-Epstein–Barr Viral Capsid Antigen IgA Antibody

“…These were based on antibodies to different antigenic components of the EBV (9,(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Attempts to use panels of antibody-based markers have generally been useful in improving the accuracy of NPC detection (13, 15, 20, 21, 29 -32 ).…”

Serum Antibody Response to Lytic and Latent Epstein-Barr Virus Antigens in Undifferentiated Nasopharyngeal Carcinoma Patients from an Area of Nonendemicity

“…The ZEBRA protein, the master activator of EBV reactivation, was also employed for UCNT serological diagnosis by different authors (19,20,25), with sensitivities of 75 to 87% depending on the different assays used. Using a peptide-based ELISA, we found a high specificity (94.4%) and almost the same sensitivity (61%) observed in NPC sera from Chinese patients (63%) (39).…”

“…Antibodies against ZEBRA are a marker of EBV reactivation and are regularly found in UCNT patients (65 to 87%), but only rarely among healthy people (19,20,25,39).…”