Evaluation of a Multianalyte Profiling Assay and an Enzyme-Linked Immunosorbent Assay for Serological Examination of Epstein-Barr Virus-Specific Antibody Responses in Diagnosis of Nasopharyngeal Carcinoma

Gu, Ai Di; Mo, Hao Yuan; Xie, Yan; Peng, Rou Jun; Bei, Jin Xin; Peng, Juan; Li, Miao Yan; Chen, Li Zhen; Feng, Qi Sheng; Jia, Wei Hua; Zeng, Yi Xin

doi:10.1128/cvi.00135-08

Cited by 15 publications

(10 citation statements)

References 35 publications

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“…The definition and serological use of these EBV peptide reagents has been described before [17,18]. In early studies we defined that the predominant response to Zta in BL patients was directed against the N-terminal domain, spanning amino acids 1-44 (Middeldorp, unpublished data).…”

Section: Methodsmentioning

confidence: 99%

Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

Asito

Piriou

Odada

et al. 2010

Infect Agents Cancer

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BackgroundEndemic Burkitt's lymphoma (BL) is an extranodal tumor appearing predominantly in the jaw in younger children while abdominal tumors predominate with increasing age. Previous studies have identified elevated levels of antibodies to Plasmodium falciparum schizont extracts and Epstein-Barr virus (EBV) viral capsid antigens (VCA) in endemic BL relative to malaria exposed controls. However, these studies have neither determined if there were any differences based on the site of clinical presentation of the tumor nor examined a broader panel of EBV and P. falciparum antigens.MethodsWe used a suspension bead Luminex assay to measure the IgG levels against EBV antigens, VCA, EAd, EBNA-1 and Zta as well as P. falciparum MSP-1, LSA-1, and AMA-1 antigens in children with BL (n = 32) and in population-based age-and sex-matched controls (n = 25) from a malaria endemic region in Western Kenya with high incidence of BL. EBV viral load in plasma was determined by quantitative PCR.ResultsRelative to healthy controls, BL patients had significantly increased anti-Zta (p = 0.0017) and VCA IgG levels (p < 0.0001) and plasma EBV viral loads (p < 0.0001). In contrast, comparable IgG levels to all P. falciparum antigens tested were observed in BL patients compared to controls. Interestingly, when we grouped BL patients into those presenting with abdominal tumors or with jaw tumors, we observed significantly higher levels of anti-Zta IgG levels (p < 0.0065) and plasma EBV viral loads (p < 0.033) in patients with abdominal tumors compared to patients with jaw tumors.ConclusionElevated antibodies to Zta and elevated plasma EBV viral load could be relevant biomarkers for BL and could also be used to confirm BL presenting in the abdominal region.

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Section: Methodsmentioning

confidence: 99%

Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

Asito

Piriou

Odada

et al. 2010

Infect Agents Cancer

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“…Tetanus toxoid (TT) antigen (Calbiochem, Darmstadt, Germany) was used as a control since mothers are routinely immunized against tetanus during pregnancy. The choices of the above-mentioned antigens were based on their well-characterized serological profiles as previously described (13,32,33).…”

Section: Methodsmentioning

confidence: 99%

Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy

Ogolla

Daud

Asito

et al. 2015

Clin Vaccine Immunol

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h Over 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malaria in utero. Levels of EBV-and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers. In utero malaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis, in utero malaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P ‫؍‬ 0.0234 and P ‫؍‬ 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection. E ndemic Burkitt's lymphoma (eBL) is a distinct form of nonHodgkin's lymphoma and is the most common pediatric malignancy in regions of malaria endemicity of sub-Saharan Africa (1). Both infection with Epstein-Barr virus (EBV) and repeated episodes of Plasmodium falciparum malaria are known risk factors for eBL (2), but the mechanism(s) by which these two agents interact to promote the emergence of malignant B cell clones has not been elucidated. Recently, we found that infants from a region of malaria endemicity of western Kenya were infected with EBV by 6 months of age (3). Living in regions of malaria endemicity was a predictor of this early age of primary infection. This aberrant primary EBV infection may set the stage for lymphoma development, as previously hypothesized (4-6).The lytic and latent phases of the EBV life cycle induce distinct antibodies in response to specific lytic and latent antigens. Anti-EBV nuclear antigen-1 (EBNA1) antibodies are produced against EBNA1, the only antigen expressed in latently infected memory B cells and in eBL tumors (7). Anti-viral capsid antigen (anti-VCA), anti-early antigen (ant...

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“…(Table 3)This might be due to the different sources of antigens.This aspectis also supported by Gu. [25]The EBV VCA antigen consists of several proteins, such as gp125, p18, and p23. As regards the measurement of IgA, except Euroimmun that uses gp125, other assays use the p18 peptide or other protein mixtures(Antu,New Industries,YHLO).The results depend on the use of a range of different antigens producing different serological responses.…”

Section: Discussionmentioning

confidence: 99%

Preliminary evaluation of a candidate international reference for Epstein–Barr virus capsid antigen immunoglobulin A in China

Chen

Zhong²,

et al. 2020

Preprint

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Background: The detection of the Epstein–Barr capsid antigen (VCA) immunoglobulin A (IgA) is widely used inthe diagnosis of nasopharyngeal carcinoma (NPC),but a reference standard for evaluating the presence of VCA-IgA isnot yet available. Therefore, a reference standard is urgently needed for a uniform and quantitative detection of VCA-IgA.Methods: A mixed reference serum from three NPC patients diluted with healthy subject serum was made as a potential first international standard for VCA-IgA. VCA-IgA was detected in twenty NPC patients by four ELISA kits and two chemiluminescent immunoassays kits using the reference as a calibration curve. The performance of these six kits was evaluated, and the quantitative results were compared. Results: Our results showed a good linearity of the reference in different kits. Without reference, the difference of the total coefficient of variation (from 3.98% to 43.11%) and Within-run coefficient of variation (from 2.47% to 19.66%) was large in the 6 kits. The positive and negative coincidence rate between the 6 kits and indirect immunofluorescence for NPC diagnosis was 75% overall agreement, but a difference among the six kits was found, ranging from 55% to 90%. The concentration of VCA-IgA in the 20 NPC samples led in the division into three categories such as negative, low, or medium/high positive, but these concentrations were significantly different within these three categories depending on the kit used of the 6 considered. However,a good correlation (R2=0.986) was observed between Antu and Beier ELISA kits.Conclusions: The reference serum mightbe used as a reference standard for a better comparison of the results from different kits/laboratories.However, the quantitative results of some kits are still inconsistent due to the diversity of VCA antigens.

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Evaluation of a Multianalyte Profiling Assay and an Enzyme-Linked Immunosorbent Assay for Serological Examination of Epstein-Barr Virus-Specific Antibody Responses in Diagnosis of Nasopharyngeal Carcinoma

Abstract: Assessment of antibody responses to Epstein-Barr virus (EBV) antigens has been used to assist in naso-

Cited by 15 publications

References 35 publications

Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

Elevated anti-Zta IgG levels and EBV viral load are associated with site of tumor presentation in endemic Burkitt's lymphoma patients: a case control study

Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy

Preliminary evaluation of a candidate international reference for Epstein–Barr virus capsid antigen immunoglobulin A in China

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