Enzyme‐Linked immunosorbent assay (ELISA) for IgA and IgG antibodies to epstein‐barr‐virus ribonucleotide reductase in patients with nasopharyngeal carcinoma

Fones-Tan, A.; Chan, Ssc; Tsao, Sai‐Wah; Gan, L. H.; Tan, W. H.; Li, B.; Khong, PL; Ye, Gan

doi:10.1002/ijc.2910590604

Cited by 16 publications

(14 citation statements)

References 18 publications

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“…Recent studies have shown that the infection of Epstein‐Barr virus has a close relationship to the incidence of undifferentiated carcinoma, nonkeratinizing carcinoma (NKC), and KSCC of the nasopharynx, whereas few studies have reported its relationship to NACC 19–21 . Previous studies demonstrated that the EBV infection percentage in nasopharyngeal NKC and KSCC was 81.0%‐100.0% in Asia 21–23 . However, this study showed that EA‐IgA, VCA‐IgA, and EBV DNase antibody levels in plasma were positive in a small group of patients, and the positive percentages were 13.3%, 25.0%, and 42.9%, respectively.…”

Section: Discussionmentioning

confidence: 60%

Adenoid Cystic Carcinoma of the Nasopharynx: 27‐Year Experience

et al. 2008

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Section: Discussionmentioning

confidence: 60%

Adenoid Cystic Carcinoma of the Nasopharynx: 27‐Year Experience

et al. 2008

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“…Although the sensitivity of existing assays has been reported, [36][37][38][39][40][41] few studies have been conducted for the purpose of screening high-risk populations and determining whether their high sensitivities in diagnosis are consistent in screening conditions. Current use of EBV viral capsid antigen (VCA) immunoglobulin A (IgA) for screening in familial NPC yields 83% sensitivity and 87% specificity.…”

Section: Discussionmentioning

confidence: 99%

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

Wong

Kong

Tsang

et al. 2011

Cancer

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BACKGROUND: Epstein-Barr virus (EBV) microRNAs are abundant in nasopharyngeal carcinoma (NPC) tumors. With recent advances in serum microRNA detection, the distinct presence of EBV microRNAs in serum could aid in screening endemic regions for NPC. A proposed network of genes targeted by these microRNAs could also shed light on EBV-associated tumorigenesis. METHODS: MicroRNA microarray profiling of 5 paired NPC biopsies was followed by validation of 12 up-regulated EBV microRNAs (BART1-3p, 2-5p, 5, 6-5p, 6-3p, 7, 8, 9, 14, 17-5p, 18-5p, 19-3p) in 15 additional cases by real-time polymerase chain reaction. Tumor (cellular) and serum microRNA copy numbers from the same 15 patients were correlated. Expression of the same microRNAs were also examined in EBV-positive cell lines C666 and NP460hTERTþEBV. Bioinformatic tools helped predict cellular target genes, which were later confirmed by gene expression analysis. RESULTS: The authors' high-throughput approach shows that EBV microRNAs are generally more up-regulated than microRNAs of human origin. Twenty-nine of 39 EBV microRNAs were significantly up-regulated in tumor versus their nontumor biopsies (P < .05). Upon successfully validating 12 selected EBV microRNAs in 15 additional paired NPC cases, the authors found that their distinct presence in the serum of NPC patients positively correlated with cellular copy numbers of EBV microRNAs. Further investigation of potential EBV microRNA target genes revealed inhibition of tumor suppressor genes (eg, PTEN) and extensive deregulation of several pathways frequently involved in NPC (eg, Wnt signaling). CONCLUSIONS: Increasing knowledge of host-virus interaction via microRNAs may provide feasible explanations underlying NPC tumorigenesis along with the development of biomarkers for screening high-risk populations. Cancer 2012;118:698-

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“…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). However, single markers may not be sufficient to identify all individual NPC patients in view of the observed diversity of antibody reactivity among individual NPC patients.…”

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confidence: 99%

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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Enzyme‐Linked immunosorbent assay (ELISA) for IgA and IgG antibodies to epstein‐barr‐virus ribonucleotide reductase in patients with nasopharyngeal carcinoma

Cited by 16 publications

References 18 publications

Adenoid Cystic Carcinoma of the Nasopharynx: 27‐Year Experience

Adenoid Cystic Carcinoma of the Nasopharynx: 27‐Year Experience

Profiling of Epstein‐Barr virus‐encoded microRNAs in nasopharyngeal carcinoma reveals potential biomarkers and oncomirs

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

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