Comparison of three different serological techniques for primary diagnosis and monitoring of nasopharyngeal carcinoma in two age groups from Tunisia

Karray, H.; Ayadi, Wajdi; Fki, L.; Hammami, Adnane; Daoud, J.; Drira, M.; Frikha, M.; Jlidi, R.; Middeldorp, Jaap M.

doi:10.1002/jmv.20310

Cited by 63 publications

(77 citation statements)

References 35 publications

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“…Lytic-cycle products are rarely expressed in the NPC tumor cells but may originate from viral replication in differentiating NPC cells (51). The assessment of anti-EBNA1, anti-EA, and anti-VCA antibodies requires separate assays, each contributing to NPC diagnosis (23). Individual NPC patients may respond quite differently to EBV lytic-cycle proteins, but the small capsid protein VCA-p18, encoded by the BFRF3 reading frame, is a highly prevalent target for antibody responses, including IgG and IgA (3,9,13,23,35,44).…”

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confidence: 99%

“…The assessment of anti-EBNA1, anti-EA, and anti-VCA antibodies requires separate assays, each contributing to NPC diagnosis (23). Individual NPC patients may respond quite differently to EBV lytic-cycle proteins, but the small capsid protein VCA-p18, encoded by the BFRF3 reading frame, is a highly prevalent target for antibody responses, including IgG and IgA (3,9,13,23,35,44). However, high titers of IgG against EA/VCA are not specific for NPC and can be observed in other EBV-linked diseases as well (18).…”

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confidence: 99%

“…Standardized EBV IgA ELISAs suited for field screening require the availability of high-quality, reproducible, and preferably cheap EBV antigens comprising the immunodominant markers for EBV IgA antibodies. Previously reported EBV antigens for ELISA include EBV cell extracts (11,12,46), purified native or recombinant EBV proteins (3,7,9), and synthetic peptides (16,23,44). Among the defined EBV antigens proposed as markers in ELISA are thymidine kinase (7,25), DNase (41), ribonucleotide reductase (15), ZEBRA (9,22), VCA-p18 (35,44), EBNA1 (16,21), and EAd-p47/p138 (14).…”

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Single-Assay Combination of Epstein-Barr Virus (EBV) EBNA1- and Viral Capsid Antigen-p18-Derived Synthetic Peptides for Measuring Anti-EBV Immunoglobulin G (IgG) and IgA Antibody Levels in Sera from Nasopharyngeal Carcinoma Patients: Options for Field Screening

et al. 2006

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Assessment of immunoglobulin A (IgA) antibody responses to various Epstein-Barr virus (EBV) antigencomplexes, usually involving multiple serological assays, is important for the early diagnosis of nasopharyngeal carcinoma (NPC). Through combination of two synthetic peptides representing immunodominant epitopes of EBNA1 and viral capsid antigen (VCA)-p18 we developed a one-step sandwich enzyme-linked immunosorbent assay (ELISA) for the specific detection of EBV reactive IgG and IgA antibodies in NPC patients (EBV IgG/IgA ELISA). Sera were obtained from healthy donors (n ‫؍‬ 367), non-NPC head and neck cancer patients (n ‫؍‬ 43), and biopsy-proven NPC patients (n ‫؍‬ 296) of Indonesian and Chinese origin. Higher values of optical density at 450 nm for EBV IgG were observed in NPC patients compared to the healthy EBV carriers, but the large overlap limits its use for NPC diagnosis. Using either EBNA1 or VCA-p18 peptides alone IgA ELISA correctly identified 88.5% and 79.8% of Indonesian NPC patients, with specificities of 80.1% and 70.9%, whereas combined single-well coating with both peptides yielded sensitivity and specificity values of 90.1 and 85.4%, respectively. The positive and negative predictive values (PPV and NPV, respectively) for the combined EBNA1 plus VCA EBV IgA ELISA were 78.7% and 93.9%, respectively. In the Indonesia panel, the level of EBV IgA reactivity was not associated with NPC tumor size, lymph node involvement, and metastasis stage, sex, and age group. In the China panel the sensitivity/specificity values were 86.2/92.0% (EBNA1 IgA) and 84.1/90.3% (VCA-p18 IgA) for single-peptide assays and 95.1/90.6% for the combined VCA plus EBNA1 IgA ELISA, with a PPV and an NPV for the combined EBV IgA ELISA of 95.6 and 89.3%, respectively. Virtually all NPC patients had abnormal anti-EBV IgG diversity patterns as determined by immunoblot analysis. On the other hand, healthy EBV carriers with positive EBV IgA ELISA result showed normal IgG diversity patterns. By using EBV IgG immunoblot diversity as confirmation assay for EBV IgA ELISA-positive samples, the sensitivity and specificity for NPC diagnosis increased to 98% and 99.2%, respectively, in the Indonesian NPC samples. The use of these combined methods for seroepidemiological screening studies is proposed.

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Single-Assay Combination of Epstein-Barr Virus (EBV) EBNA1- and Viral Capsid Antigen-p18-Derived Synthetic Peptides for Measuring Anti-EBV Immunoglobulin G (IgG) and IgA Antibody Levels in Sera from Nasopharyngeal Carcinoma Patients: Options for Field Screening

et al. 2006

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“…Combined detection of anti-NA1, anti-early antigen (EA), anti-viral capsid antigen and anti-replication and transcription activator increases the sensitivity and has been considered as a useful serological method for NPC screening and diagnosis (16)(17)(18)(19)(20). Salivary IgA antibody titers were previously reported to be increased in response to EA, gp340 or NA1-p107 in healthy individuals compared with patients with NPC.…”

Section: Discussionmentioning

confidence: 99%

Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

Jiang

et al. 2017

Oncology Letters

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Abstract. Nuclear antigen-1 (NA1) protein of Epstein-Barr virus (EBV) is expressed in EBV-infected cells in the microenvironment of cancer. Since immune cells infiltrate abundantly in nasopharyngeal carcinoma (NPC) tumor tissues, we hypothesized that the local tumor microenvironment may perform an important role in the production of antibodies directed at NA1. Furthermore, we hypothesized that anti-NA1 antibody originating in the local microenvironment could be secreted into the saliva of patients with NPC. In the present study, 20 healthy controls and 39 patients with NPC treated with intensity-modulated radiation therapy were recruited for the study. Saliva and serum samples were collected from the NPC patients, and nasopharyngeal tissue samples from the patients with NPC. The titers of anti-NA1 antibody [immunoglobulin A (IgA)] were determined by ELISA. Expression of NA1, human leukocyte antigen-antigen D related (HLA-DR), cluster of differentiation (CD)80, CD86, CD3, CD4, CD19 and IgA was detected by immunohistochemical staining on paraffin-embedded nasopharyngeal tissue sections. Anti-NA1 antibodies were detected in the serum and saliva samples of the patients with NPC. In infiltrating cells, expression of HLA-DR, CD80, CD86, CD3, CD4, CD19 and IgA was detected, indicating that dendritic cells, T lymphocytes and B lymphocytes were all present in the local tumor tissues. Furthermore, expression of EBNA1 protein was detected on the membrane of the NPC tumor cells. Therefore, the NPC tumor microenvironment has the potential to initiate a humoral response to EBNA1 by producing IgA antibodies.

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“…Specific antibody responses to EBV proteins have become a powerful tool to detect reactivation of this virus in human body. Previous studies reported various serological biomarkers as prognostic factors with inconsistent results (Karray et al, 2005;Liu et el., 2004;Neel and Taylor, 1990;Yip et al, 1994;de Vathaire et al, 1988). Fan et al (2004) reported the use of IgA early antigen (EA) serology to predict post treatment outcome.…”

Section: Discussionmentioning

confidence: 99%

The prognostic value of IgA/[EBNA1+VCA-p18] on survival of nasopharyngeal cancer patients

Taroeno-Hariadi¹,

Kurnianda²,

Hariwiyanto³

et al. 2014

J. Cancer Res. Exp. Oncol.

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Comparison of three different serological techniques for primary diagnosis and monitoring of nasopharyngeal carcinoma in two age groups from Tunisia

Cited by 63 publications

References 35 publications

Single-Assay Combination of Epstein-Barr Virus (EBV) EBNA1- and Viral Capsid Antigen-p18-Derived Synthetic Peptides for Measuring Anti-EBV Immunoglobulin G (IgG) and IgA Antibody Levels in Sera from Nasopharyngeal Carcinoma Patients: Options for Field Screening

Single-Assay Combination of Epstein-Barr Virus (EBV) EBNA1- and Viral Capsid Antigen-p18-Derived Synthetic Peptides for Measuring Anti-EBV Immunoglobulin G (IgG) and IgA Antibody Levels in Sera from Nasopharyngeal Carcinoma Patients: Options for Field Screening

Tumor microenvironment contributes to Epstein-Barr virus anti-nuclear antigen-1 antibody production in nasopharyngeal carcinoma

The prognostic value of IgA/[EBNA1+VCA-p18] on survival of nasopharyngeal cancer patients

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