IgA antibodies against the Epstein‐Barr nuclear antigen1 as a valuable biomarker for the diagnosis of nasopharyngeal carcinoma in Tunisian patients

Abstract

Serological tests for Epstein-Barr virus (EBV) have been used for many years as diagnostic predictors of nasopharyngeal carcinoma. It has been shown previously that the conventional immunofluorescence assay has a limited diagnostic value, especially in young patients from North African area. In the search for more reliable immunoglobulin (Ig) G or IgA antibody markers for the diagnosis of nasopharyngeal carcinoma, immunoblot analysis was performed using a full spectrum of EBV proteins. Sera were collected from 108 patients with nasopharyngeal carcinoma and three control groups composed of 18 patients with lymphoma, 18 other patients with autoimmune diseases and 55 healthy EBV carriers. It was observed that the IgA Epstein-Barr nuclear antigen 1 (EBNA1), IgA early antigen (EA)-p138 and IgG EA-p138 antibodies represent the most specific anti-EBV responses in either young or older patients with nasopharyngeal carcinoma which yield higher positive rates compared to the three control groups. Since the IgA EBNA1 response showed the highest sensitivity value for the detection of nasopharyngeal carcinoma, a novel enzyme-linked immunosorbent assay (ELISA) was established using a GST-EBNA1 protein expressed in bacteria, containing the P-threonine EBNA1 subtype cloned from DNA EBV sequence of C15 xenograft cells. Detection rates were 85.7% and 94.9% in young and older patients with nasopharyngeal carcinoma respectively, while only 3.6%, 11.1%, and 16.6% in healthy EBV carriers, patients with lymphoma and patients with autoimmune diseases, respectively. Thus, IgA EBNA1 ELISA may be useful for early diagnosis and mass screening of nasopharyngeal carcinoma in Tunisia even in young patients.

Differential features of nasopharyngeal carcinoma in children and adults: A SEER study

“…Among distinct biologic features in young patients with NPC are higher levels of EBV latent membrane protein expression 13, lower levels of the antiapoptotic BCL‐2 expression 14, and greater c‐KIT protein expression. Furthermore, young patients had lower IgA antibody responses against ZEBRA ( P < 0.01), VCA‐p40 ( P = 0.05), and EA‐p47/54 ( P = 0.04) antigens 15. On the other hand, there does not seem to be a viral polymorphism more consistently associated with juvenile or adult NPC 16.…”

Fluctuations of Epstein-Barr Virus Serological Antibodies and Risk for Nasopharyngeal Carcinoma: A Prospective Screening Study with a 20-Year Follow-Up

“…In 1973, presence of EBV genomes was demonstrated in epithelial NPC cells [18] and EBV-related antigens were detected in the tumor cells of all NPC patients [26]. Subsequently, the expression of the viral genome in non-keratinising NPC has been studied extensively in areas with NPC epidemic [14], [16], [27] and major types of viral expression proteins have been found, e.g., EBNA1 [28]–[30], LMP1 [15], [31]–[34] and LMP2A [31]. Moreover, in case-control studies, NPC cases showed significantly higher antibody titers to EBV antigens than controls in several retrospective studies [11], [19], [35]–[38].…”

Circulating nucleic acids as a new diagnostic tool

“…The association of a viral infection and the initiation of certain types of cancer makes the detection of viral nucleic acids an interesting potential method. There are several pieces of evidence for the presence of Epstein-Barr virus (EBV) DNA in the blood of nasopharyngeal carcinoma patients [59,60] and for the presence of Human Papilloma virus (HPV) DNA in patients with cervical cancer [61] or head and neck squamous cell carcinoma [62].…”