title: 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) is highly 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.
authors.affiliation: Microbiology-Immunology and Virology Unit, Centro di Riferimento Oncologico, Istituto di Recovero e Cura a Carattere Scientifico, Aviano, Italy. rtedeschi@cro.it
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Tedeschi
authors.forename: Elisa
authors.initials: E
authors.lastname: Pin
authors.forename: Debora
authors.initials: D
authors.lastname: Martorelli
authors.forename: Ettore
authors.initials: E
authors.lastname: Bidoli
authors.forename: Alessia
authors.initials: A
authors.lastname: Marus
authors.forename: Chiara
authors.initials: C
authors.lastname: Pratesi
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Bortolin
authors.forename: Stefania
authors.initials: S
authors.lastname: Zanussi
authors.forename: Emanuela
authors.initials: E
authors.lastname: Vaccher
authors.forename: Riccardo
authors.initials: R
authors.lastname: Dolcetti
authors.forename: Paolo
authors.initials: P
authors.lastname: De Paoli
mesh_terms: D000914:Antibodies, Viral / Q000096:biosynthesis* / Q000097:blood; D000956:Antigens, Viral / Q000276:immunology*; D036022:Capsid Proteins / Q000276:immunology*; D002277:Carcinoma / Q000276:immunology* / Q000821:virology; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology* / Q000276:immunology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000276:immunology*; D009303:Nasopharyngeal Neoplasms / Q000276:immunology* / Q000821:virology; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D000956:Antigens, Viral; D036022:Capsid Proteins; C041788:Epstein-Barr viral capsid antigen; C083204:Epstein-Barr virus early antigen diffuse component