title: Aberrant Epstein-Barr virus antibody patterns and chronic lymphocytic leukemia in a Spanish multicentric case-control study.
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.
authors.affiliation: Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Av. Gran Via 199 - 203, 2°; 08908 L'Hospitalet de Llobregat, Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Delphine
authors.initials: D
authors.lastname: Casabonne
authors.affiliation: Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Av. Gran Via 199 - 203, 2°; 08908 L'Hospitalet de Llobregat, Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Benavente
authors.affiliation: Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Av. Gran Via 199 - 203, 2°; 08908 L'Hospitalet de Llobregat, Barcelona, Spain.
authors.forename: Claudia
authors.initials: C
authors.lastname: Robles
authors.affiliation: Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Av. Gran Via 199 - 203, 2°; 08908 L'Hospitalet de Llobregat, Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Costas
authors.affiliation: Department of Pathology, Hospital Universitari de Bellvitge, L'Hospitalet de LLobregat, Barcelona, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Alonso
authors.affiliation: Hematology, L' Hospitalet de Llobregat, IDIBELL, Institut Català d' Oncologia, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Gonzalez-Barca
authors.affiliation: Faculty of Medicine, University of Oviedo, Oviedo, Asturias.
authors.forename: Adonina
authors.initials: A
authors.lastname: Tardón
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain ; Faculty of Medicine, University of Cantabria- IDIVAL, Santander, Spain.
authors.forename: Trinidad
authors.initials: T
authors.lastname: Dierssen-Sotos
authors.affiliation: Hematology, Hospital del Mar, Barcelona, Spain.
authors.forename: Eva Gimeno
authors.initials: EG
authors.lastname: Vázquez
authors.affiliation: Hematopathology Unit, Pathology Department, Hospital Clínic and University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.affiliation: Hematopathology Unit, Pathology Department, Hospital Clínic and University of Barcelona, Institute of Biomedical Research August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain ; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain ; Universitat Pompeu Fabra (UPF), Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Gemma
authors.initials: G
authors.lastname: Castaño-Vinyals
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain ; National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain ; Instituto de Investigación Sanitaria (IIS) of Hierro, Majadahonda, Spain.
authors.forename: Nuria
authors.initials: N
authors.lastname: Aragones
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain ; National Center for Epidemiology, Carlos III Institute of Health, Madrid, Spain ; Instituto de Investigación Sanitaria (IIS) of Hierro, Majadahonda, Spain.
authors.forename: Marina
authors.initials: M
authors.lastname: Pollan
authors.affiliation: Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain ; Hospital del Mar Medical Research Institute (IMIM), Barcelona, Spain ; Universitat Pompeu Fabra (UPF), Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain ; National School of Public Health, Athens, Greece.
authors.forename: Manolis
authors.initials: M
authors.lastname: Kogevinas
authors.affiliation: Department Pathology, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Hedy
authors.initials: H
authors.lastname: Juwana
authors.affiliation: Department Pathology, VU University medical center, Amsterdam, The Netherlands.
authors.forename: Jaap
authors.initials: J
authors.lastname: Middeldorp
authors.affiliation: Unit of Infections and Cancer (UNIC), IDIBELL, Institut Català d'Oncologia, L'Hospitalet de Llobregat, Av. Gran Via 199 - 203, 2°; 08908 L'Hospitalet de Llobregat, Barcelona, Spain ; CIBER Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjose
keywords: Case-control; Chronic lymphocytic leukemia; Epstein-Barr virus; Serology; Smoking