Common infectious agents and monoclonal B-cell lymphocytosis: a cross-sectional epidemiological study among healthy adults

PLoS One. 2012;7(12):e52808. doi: 10.1371/journal.pone.0052808. Epub 2012 Dec 28.

Abstract

Background: Risk factors associated with monoclonal B-cell lymphocytosis (MBL), a potential precursor of chronic lymphocytic leukaemia (CLL), remain unknown.

Methods: Using a cross-sectional study design, we investigated demographic, medical and behavioural risk factors associated with MBL. "Low-count" MBL (cases) were defined as individuals with very low median absolute count of clonal B-cells, identified from screening of healthy individuals and the remainder classified as controls. 452 individuals completed a questionnaire with their general practitioner, both blind to the MBL status of the subject. Odds ratios (OR) and 95% confidence interval (CI) for MBL were estimated by means of unconditional logistic regression adjusted for confounding factors.

Results: MBL were detected in 72/452 subjects (16%). Increasing age was strongly associated with MBL (P-trend<0.001). MBL was significantly less common among individuals vaccinated against pneumococcal or influenza (OR 0.49, 95% confidence interval (CI): 0.25 to 0.95; P-value=0.03 and OR: 0.52, 95% CI: 0.29 to 0.93, P-value=0.03, respectively). Albeit based on small numbers, cases were more likely to report infectious diseases among their children, respiratory disease among their siblings and personal history of pneumonia and meningitis. No other distinguishing epidemiological features were identified except for family history of cancer and an inverse relationship with diabetes treatment. All associations described above were retained after restricting the analysis to CLL-like MBL.

Conclusion: Overall, these findings suggest that exposure to infectious agents leading to serious clinical manifestations in the patient or its surroundings may trigger immune events leading to MBL. This exploratory study provides initial insights and directions for future research related to MBL, a potential precursor of chronic lymphocytic leukaemia. Further work is warranted to confirm these findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • B-Lymphocytes* / metabolism
  • Cross-Sectional Studies
  • Female
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / epidemiology
  • Leukemia, Lymphocytic, Chronic, B-Cell / etiology
  • Lymphocyte Count
  • Lymphocytosis / epidemiology*
  • Lymphocytosis / etiology
  • Male
  • Middle Aged
  • Odds Ratio
  • Prevalence
  • Risk Factors

Grants and funding

This work was financially supported by the following grants: Red Temática de Investigación Cooperativa en Cáncer del Instituto de Salud Carlos III - FONDOS FEDER (RD06/0020/0035, 2006-RET2039-O, CIBERESP 06/02/0073); FIS PI06/0824-FEDER, PS09/02430-FEDER and PI11/01810-FEDER, from the Fondo de Investigación Sanitaria, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain; GRS206/A/08 from the Gerencia Regional de Salud de Castilla y León and Ayuda al Grupo GR37 de Excelencia de Castilla y León, Consejería de Educación, and SAN/1778/2009, Consejería de Sanidad, Junta de Castilla y León, Valladolid, Spain; and Agència de Gestió d’Ajuts Universitaris i de Recerca Generalitat de Catalunya (AGAUR 2009SGR1465). AR-C is supported by a grant from Fundación Científica de la Asociación Española contra el Cáncer. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.