title: Epstein-Barr virus infection and risk of lymphoma: immunoblot analysis of antibody responses against EBV-related proteins in a large series of lymphoma subjects and matched controls.
abstract: Epstein-Barr Virus (EBV) is consistently associated with distinct lymphoproliferative malignancies and aberrant EBV antibody patterns are found in most EBV cancer patients. We evaluate the detection of an abnormal reactive serological pattern to EBV (ab_EBV) infection and the risk of lymphoma in a multicentric case-control study. Serum samples were collected at study entry from 1,085 incident lymphoma cases from Spain, France, Germany, Czech Republic, Italy and 1,153 age, sex and country matched controls. EBV immunoglobulin G (IgG) serostatus was evaluated through a peptide-based ELISA combining immunodominant epitopes of EBNA1 (BKRF1) and VCA-p18 (BFRF3). Further, immunoblot analysis was performed to evaluate distinct antibody diversity patterns to EBV early antigens (EA), besides EBNA1, VCA-p18, VCA-p40 (BdRF1) and Zebra (BZLF1). Patients with chronic active EBV infection and aberrant EBV activity were characterized as having an abnormal reactive pattern (ab_EBV). Ab_EBV was observed in 20.9% of 2,238 included subjects with an increased proportion of cases presenting ab_EBV as compared to the control population (23.9% vs. 18.0% p = 0.001). Ab_EBV positivity was a risk factor for all lymphomas combined (odds ratio [OR] = 1.42, 95% confidence interval [CI]=1.15-1.74), and specifically for chronic lymphocytic leukaemia (OR = 2.96, 95%CI = 2.22-3.95). Lower levels of ab_EBV were observed for follicular lymphoma (OR = 0.38, 95%CI = 0.15-0.98). EBV may be involved in a larger subset of lymphomas among clinically immunocompetent subjects than previously thought, probably explained by an underlying loss of immune control of EBV latent infection. Ab_EBV is a useful tool to explore EBV imbalances preceding or paralleling possible EBV associated oncogenic events.
authors.affiliation: Servei d'Epidemiologia and Registre del Cancer, IDIBELL, Institut Catala d'Oncologia, Gran Via Km 2.7, 08907 L'Hospitalet, Barcelona, Spain. s.sanjose@iconcologia.net
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.forename: Ramon
authors.initials: R
authors.lastname: Bosch
authors.forename: Tabitha
authors.initials: T
authors.lastname: Schouten
authors.forename: Sandra
authors.initials: S
authors.lastname: Verkuijlen
authors.forename: Alexandra
authors.initials: A
authors.lastname: Nieters
authors.forename: Lenka
authors.initials: L
authors.lastname: Foretova
authors.forename: Marc
authors.initials: M
authors.lastname: Maynadié
authors.forename: Pier Luigi
authors.initials: PL
authors.lastname: Cocco
authors.forename: Anthony
authors.initials: A
authors.lastname: Staines
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Becker
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.forename: Paolo
authors.initials: P
authors.lastname: Boffetta
authors.forename: Chris Jlm
authors.initials: CJ
authors.lastname: Meijer
authors.forename: Jaap M
authors.initials: JM
authors.lastname: Middeldorp
mesh_terms: D000328:Adult; D000368:Aged; D000914:Antibodies, Viral / Q000097:blood*; D016022:Case-Control Studies; D018153:Czech Republic / Q000453:epidemiology; D004797:Enzyme-Linked Immunosorbent Assay; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000453:epidemiology* / Q000276:immunology; D005260:Female; D005602:France / Q000453:epidemiology; D005858:Germany / Q000453:epidemiology; D006801:Humans; D015151:Immunoblotting; D007074:Immunoglobulin G / Q000097:blood; D015994:Incidence; D007494:Ireland / Q000453:epidemiology; D007558:Italy / Q000453:epidemiology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000453:epidemiology / Q000821:virology; D008223:Lymphoma / Q000453:epidemiology* / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D000914:Antibodies, Viral; D007074:Immunoglobulin G