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Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study

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dc.contributor.author Casabonne, Delphine
dc.contributor.author Benavente, Yolanda
dc.contributor.author Robles Hellín, Claudia, 1980-
dc.contributor.author Costas, Laura
dc.contributor.author Alonso, Esther
dc.contributor.author González, Eva
dc.contributor.author Tardón, Adonina
dc.contributor.author Dierssen Sotos, Trinidad
dc.contributor.author Gimeno Vázquez, Eva
dc.contributor.author Aymerich, Marta
dc.contributor.author Campo, Elias
dc.contributor.author Castaño Vinyals, Gemma
dc.contributor.author Aragonés, Núria
dc.contributor.author Pollan, Marina
dc.contributor.author Kogevinas, Manolis
dc.contributor.author Juwana, Hedy
dc.contributor.author Middeldorp, Jaap
dc.contributor.author de Sanjosé, Silvia
dc.date.accessioned 2015-06-16T08:18:10Z
dc.date.available 2015-06-16T08:18:10Z
dc.date.issued 2015
dc.identifier.citation Casabonne D, Benavente Y, Robles C, Costas L, Alonso E, Gonzalez-Barca E et al. Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study. Infect Agent Cancer. 2015;10:5. DOI: 10.1186/1750-9378-10-5
dc.identifier.issn 1750-9378
dc.identifier.uri http://hdl.handle.net/10230/23825
dc.description.abstract Background: Epstein-Barr virus (EBV)-related malignancies harbour distinct serological responses to EBV antigens. We hypothesized that EBV serological patterns can be useful to identify different stages of chronic lymphocytic leukemia. Methods: Information on 150 cases with chronic lymphocytic leukemia and 157 frequency-matched (by age, sex and region) population-based controls from a Spanish multicentre case-control study was obtained. EBV immunoglobulin G serostatus was evaluated through a peptide-based ELISA and further by immunoblot analysis to EBV early antigens (EA), nuclear antigen (EBNA1), VCA-p18, VCA-p40 and Zebra. Two independent individuals categorized the serological patterns of the western blot analysis. Patients with very high response and diversity in EBV-specific polypeptides, in particular with clear responses to EA-associated proteins, were categorized as having an abnormal reactive pattern (ab_EBV). Adjusted odds ratios (OR) and 95% confidence interval (CI) were estimated using logistic regression models. Results: Almost all subjects were EBV-IgG positive (>95% of cases and controls) whereas ab_EBV patterns were detected in 23% of cases (N = 34) and 11% of controls (N = 17; OR: 2.44, 95% CI, 1.29 to 4.62; P = 0.006), particularly in intermediate/high risk patients. Although based on small numbers, the association was modified by smoking with a gradual reduction of ab_EBV-related OR for all Rai stages from never smokers to current smokers. Conclusions: Highly distinct EBV antibody diversity patterns revealed by immunoblot analysis were detected in cases compared to controls, detectable at very early stages of the disease and particularly among non smokers. This study provides further evidence of an abnormal immunological response against EBV in patients with chronic lymphocytic leukemia.
dc.description.sponsorship This work was supported by the “Acción Transversal del Cancer”, approved on the Spanish Ministry Council on the 11th October 2007, by the Instituto de Salud Carlos III (Spanish Government) (grants PI08/1770, PI08/0533, PI08/1359, PS09/00773-Cantabria, PI11/01810, PI11/02213, RCESP C03/09, RTICESP C03/10, RTIC RD06/0020/0095, RTIC RD12/0036/0056, Rio Hortega CM13/00232, SV-09-CLINIC-1 and CIBERESP), by the Fundación Marques de Valdecilla (API 10/09), by Obra Social CAJASTUR (SV-CAJASTUR-1), by the Recercaixa (2010ACUP 00310), by the Spanish Association Against Cancer (AECC) Scientific Foundation and by the Agència de Gestió d’Ajuts Universitaris i de Recerca (AGAUR)–Generalitat de Catalunya (Catalonian Government) (grants AGAUR 2009SGR1026, 2014SGR756 and 2009SGR1465). The ICGC CLL-Genome Project is funded by Spanish Ministerio de Economía y Competitividad (MINECO) through the Instituto de Salud Carlos III (ISCIII) and Red Temática de Investigación del Cáncer (RTIC RD12/0036/0036) del ISCIII. Sample collection and storage was partially supported by the Instituto de Salud Carlos III FEDER (RD09/0076/00036), Xarxa de Bancs de Tumors de Catalunya sponsored by Pla Director d’Oncologia de Catalunya (XBTC).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher BioMed Central
dc.relation.ispartof Infectious Agents and Cancer. 2015;10:5
dc.rights © 2015 Casabonne et al.; licensee BioMed Central. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.rights.uri http://creativecommons.org/licenses/by/4.0
dc.subject.other Leucèmia limfocítica crònica
dc.subject.other Virus d'Epstein-Barr
dc.title Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1186/1750-9378-10-5
dc.subject.keyword Chronic lymphocytic leukemia
dc.subject.keyword Epstein-Barr virus
dc.subject.keyword Serology
dc.subject.keyword Case-control
dc.subject.keyword Smoking
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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