Clinical Relevance of Serum Immunoglobulin A Antibodies to Epstein-Barr Virus Envelope Glycoprotein gp350 in Nasopharyngeal Carcinoma Patients

Epstein-Barr virus (EBV), the main etiological agent of infectious mononucleosis, is the most oncogenic lymphotropic human herpesvirus known. EBV has been found to be associated with a variety of lymphoid and nonlymphoid malignancies. For example, 100% of nasopharyngeal carcinomas (NPC) of the undifferentiated and poorly differentiated types are associated with EBV. NPC is a highly prevalent tumor in Southeast Asia, North Africa, and some indigenous populations of North America. Serum immunoglobulin A (IgA) antibodies to EBV capsid antigen (VCA) are of diagnostic and prognostic value for this tumor (reviewed in reference 2). These antibodies are detectable as early as is NPC and are thus critical for early diagnosis of NPC as well as for monitoring its recurrence and progression. Testing for serum anti-VCA IgA is widely used for the predictive diagnosis of NPC. A limitation of this test is that a proportion of NPC patients remain negative for these antibodies (3). As part of our work with specific immune responses to the EBV major envelope glycoprotein gp350 in different EBV-associated diseases, we compared anti-VCA IgA and gp350-specific IgA titers in sera obtained (after written and informed consent was given) from 40 Malaysian NPC patients. The sera were titrated for anti-VCA IgA and anti-gp350 IgA by immunofluorescence (1, 4). As shown in Table ​Table1,1, 70% of these sera were positive for anti-VCA IgA whereas 60% were positive for anti-gp350 IgA. Six sera positive for anti-VCA IgA (at a 1:10 dilution) were negative for gp350-specific IgA. More importantly, two serum samples (5%) that were scored negative for the presence of anti-VCA IgA (at a 1:10 dilution) were positive for gp350-specific IgA (Table ​(Table1). 1). These results suggest the existence of differential humoral immune responses to these two viral antigens in NPC patients and underscore the point that determining anti-gp350 IgA antibody titers is of diagnostic value for NPC in individuals who remain negative for anti-VCA IgA. Although anti-gp350 IgA has been detected in the sera of a low proportion of healthy EBV-seropositive individuals, their titers are significantly lower than those found in NPC sera (1, 5). In our test system, in which we use gp350-expressing T-cell clones in membrane immunofluorescence assays (1) and the cells are examined with a flow cytometer, sera from some healthy EBV-seropositive individuals were found to be positive for anti-gp350 IgA at dilutions of ≤1:10. The two above-mentioned NPC sera were positive for anti-gp350 IgA at dilutions of ≥1:20. Thus, relatively high anti-gp350 IgA titers in sera (from NPC patients) that are negative for anti-VCA IgA may be predictive of NPC, and therefore detection of IgA to gp350 should complement anti-VCA IgA tests for early diagnosis of this tumor. As EBV is associated with different lymphoproliferative disorders and various tumors, it will also be of interest to determine gp350-specific serum IgA profiles in patients with these diseases. TABLE 1 Comparison of anti-VCA IgA and anti-gp350 IgA antibody titers in sera from NPC patients