Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach

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  • dc.contributor.author Aguilar, Ruthca
  • dc.contributor.author Casabonne, Delphineca
  • dc.contributor.author O’Callaghan-Gordo, Cristinaca
  • dc.contributor.author Vidal, Martaca
  • dc.contributor.author Campo, Joseph J.ca
  • dc.contributor.author Mutalima, Noraca
  • dc.contributor.author Angov, Evelinaca
  • dc.contributor.author Dutta, Sheetijca
  • dc.contributor.author Gaur, Deepakca
  • dc.contributor.author Chitnis, Chetan E.ca
  • dc.contributor.author Chauhan, Viranderca
  • dc.contributor.author Michel, Angelikaca
  • dc.contributor.author de Sanjosé, Silviaca
  • dc.contributor.author Waterboer, Timca
  • dc.contributor.author Kogevinas, Manolisca
  • dc.contributor.author Newton, Robca
  • dc.contributor.author Dobaño, Carlotaca
  • dc.date.accessioned 2018-05-25T07:35:06Z
  • dc.date.available 2018-05-25T07:35:06Z
  • dc.date.issued 2017
  • dc.description.abstract Epstein-Barr virus (EBV) is a necessary cause of endemic Burkitt lymphoma (eBL), while the role of Plasmodium falciparum in eBL remains uncertain. This study aimed to generate new hypotheses on the interplay between both infections in the development of eBL by investigating the IgG and IgM profiles against several EBV and P. falciparum antigens. Serum samples collected in a childhood study in Malawi (2005-2006) from 442 HIV-seronegative children (271 eBL cases and 171 controls) between 1.4 and 15 years old were tested by quantitative suspension array technology against a newly developed multiplex panel combining 4 EBV antigens [Z Epstein-Barr replication activator protein (ZEBRA), early antigen-diffuse component (EA-D), EBV nuclear antigen 1, and viral capsid antigen p18 subunit (VCA-p18)] and 15 P. falciparum antigens selected for their immunogenicity, role in malaria pathogenesis, and presence in different parasite stages. Principal component analyses, multivariate logistic models, and elastic-net regressions were used. As expected, elevated levels of EBV IgG (especially against the lytic antigens ZEBRA, EA-D, and VCA-p18) were strongly associated with eBL [high vs low tertile odds ratio (OR) = 8.67, 95% confidence interval (CI) = 4.81-15.64]. Higher IgG responses to the merozoite surface protein 3 were observed in children with eBL compared with controls (OR = 1.29, 95% CI = 1.02-1.64), showing an additive interaction with EBV IgGs (OR = 10.6, 95% CI = 5.1-22.2, P = 0.05). Using elastic-net regression models, eBL serological profile was further characterized by lower IgM levels against P. falciparum preerythrocytic-stage antigen CelTOS and EBV lytic antigen VCA-p18 compared with controls. In a secondary analysis, abdominal Burkitt lymphoma had lower IgM to EBV and higher IgG to EA-D levels than cases with head involvement. Overall, this exploratory study confirmed the strong role of EBV in eBL and identified differential IgG and IgM patterns to erythrocytic vs preerythrocytic P. falciparum antigens that suggest a more persistent/chronic malaria exposure and a weaker IgM immune response in children with eBL compared with controls. Future studies should continue exploring how the malaria infection status and the immune response to P. falciparum interact with EBV infection in the development of eBL.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Aguilar R, Casabonne D, O'Callaghan-Gordo C, Vidal M, Campo JJ, Mutalima . et al. Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approach. Front Immunol. 2017 Oct 26;8:1284. DOI: 10.3389/fimmu.2017.01284
  • dc.identifier.doi http://dx.doi.org/10.3389/fimmu.2017.01284
  • dc.identifier.issn 1664-3224
  • dc.identifier.uri http://hdl.handle.net/10230/34721
  • dc.language.iso eng
  • dc.publisher Frontiersca
  • dc.relation.ispartof Frontiers in Immunology. 2017 Oct 26;8:1284
  • dc.rights Copyright © 2017 Aguilar, Casabonne, O’Callaghan-Gordo, Vidal, Campo, Mutalima, Angov, Dutta, Gaur, Chitnis, Chauhan, Michel, de Sanjosé, Waterboer, Kogevinas, Newton and Dobaño. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Epstein–Barr virus
  • dc.subject.keyword Africa
  • dc.subject.keyword IgG
  • dc.subject.keyword IgM
  • dc.subject.keyword Plasmodium falciparum
  • dc.subject.keyword Children
  • dc.subject.keyword Endemic Burkitt lymphoma
  • dc.subject.keyword Multiplex
  • dc.subject.other Virus d'Epstein-Barr
  • dc.subject.other Infeccions per virus d'Epstein-Barr
  • dc.subject.other Infants -- Malalties -- Àfrica
  • dc.subject.other Burkitt, Limfoma de
  • dc.title Assessment of the Combined Effect of Epstein-Barr Virus and Plasmodium falciparumInfections on Endemic Burkitt Lymphoma Using a Multiplex Serological Approachca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion