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

Abstract

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.

Analyses of the prognostic significance of the Epstein–Barr virus transactivator ZEBRA protein and diagnostic value of its two synthetic peptides in nasopharyngeal carcinoma

“…One may note here that EBV is able to induce the production of IL-10 by B lymphocytes; this could suppress the antiviral immunity and enhance survival and the growth of B cells (Burdin et al, 1993). However, Tedeschi et al (2007) reported that humoral immune response decreases in very advanced stage of NPC disease. This is clearly supported by our data showing a decrease in IgG-ZEBRA titer and the persistence of a stable and very low titer of IgA-EA in adult NPC patients who died.…”

Fiber Intake and Risk of Nasopharyngeal Carcinoma: A Case-Control Study

“…We are aware that lack of information on EBV status in the majority of NPC cases represents a weakness of the study (32). In the subset of cases with available EBV information, all undifferentiated NPCs were EBV-positive.…”

The extent of genetic diversity of Epstein-Barr virus and its geographic and disease patterns: A need for reappraisal

“…Several variants of Zp have been identified: Zp-P which resembles the B95-8 Zp sequence, Zp-V3, Zp-V4, and most recently Zp-PV (Gutierrez et al, 2002; Martini et al, 2007). Table 8 summarizes the distribution of Zp variants across geographic regions and health conditions (Gutierrez et al, 2002; Martini et al, 2007; Tong et al, 2003). Among controls studied, the prototype Zp-P was observed more commonly in the Americas and Europe than in China, where an almost even split was observed in the prevalence of the Zp-P and Zp-V3 variants.…”