Epstein-Barr virus (EBV)-associated undifferentiated carcinoma of the nasopharyngeal type (UCNT) ishighly prevalent in southeast China, where immunoglobulin A (IgA) antibodies to viral capsid antigen and early antigen (EA) represent important markers, routinely used to assist in diagnosing this malignancy. Our study aimed at determining the EBV serological profiles of 78 UCNT patients from Italy, an area of nonendemicity for this tumor, using different assays specific for both lytic and latent EBV antigens. Serum IgA against both EA and EBNA1 and IgG and IgA to the latent membrane protein 1 (LMP1), to EA, and to the EBV transactivator ZEBRA protein were assessed. These serological responses were then evaluated according to the clinicopathologic parameters at diagnosis. The sensitivities of the IgG assays were 37.7% for LMP1, 73.6% for EA, and 61.0% for ZEBRA. EA/EBNA1 IgA reactivity was 84.4%, and a high association (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.7 to 4.0) with UCNT was observed. When EBV serological reactivities were analyzed according to the tumor, node, and metastasis staging system (TNM), a statistically significant association was found between N stage and IgG antibody rates for EA (OR, 3.6; 95% CI, 1.2 to 10.9) and ZEBRA (OR, 2.6; 95% CI, 1.2 to 5.5) and between M stage and IgG antibody rates for ZEBRA (OR, 7.1; 95% CI, 3.2 to 16.0) and LMP1 (OR, 14.0; 95% CI, 1.8 to 110.9). Our results show that no single serological marker allows the detection of all UCNT cases. EA/EBNA1 IgA represents a reliable marker for diagnosis, with a high predictive value also in areas where UCNT is not endemic, such as Italy. The analysis of serological results according to TNM classification is consistent with a progressive impairment of humoral immune response to EBV as the disease advances and may be used to improve the accuracy of diagnosis.
The Epstein-Barr virus BZLF1-encoded replication activator (ZEBRA) is a key mediator of reactivation from latency to the viral productive cycle. In the present study, the serum antibody responses against three defined ZEBRA epitopes (designated ZEBRA-1, -19, and -22) were determined for 50 human immunodeficiency virus (HIV)-seropositive patients and 100 matched healthy control subjects. The anti-ZEBRA responses were more commonly found among HIV-seropositive patients than among healthy controls for all the three ZEBRA epitopes tested (P < 0.0003, P < 0.003, and P < 0.001, respectively). Comparison of ZEBRA antibody levels with the degree of immunodeficiency (CD4 cell counts), CDC grouping, and HIV p24 antigen positivity showed little association, suggesting that induction of ZEBRA antibodies is an early event after HIV infection.
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