title: Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression.
abstract: Patients diagnosed with chronic lymphocytic leukemia (CLL) display a high incidence of infections due to an associated immunodeficiency that includes hypogammaglobulinemia. A higher risk of infections has also been recently reported for high-count monoclonal B-cell lymphocytosis, while no information is available in low-count monoclonal B-cell lymphocytosis. Here, we evaluated the status of the humoral immune system in patients with chronic lymphocytic leukemia (n=58), as well as in low- (n=71) and high- (n=29) count monoclonal B-cell lymphocytosisversushealthy donors (n=91). Total free plasma immunoglobulin titers and specific levels of antibodies against cytomegalovirus, Epstein-Barr virus, influenza andS.pneumoniaewere measured by nephelometry and ELISA-based techniques, respectively. Overall, our results show that both CLL and high-count monoclonal B-cell lymphocytosis patients, but not low-count monoclonal B-cell lymphocytosis subjects, present with relatively high levels of antibodies specific for the latent viruses investigated, associated with progressively lower levels ofS.pneumoniae-specific immunoglobulins. These findings probably reflect asymptomatic chronic reactivation of humoral immune responses against host viruses associated with expanded virus-specific antibody levels and progressively decreased protection against other micro-organisms, denoting a severe humoral immunodeficiency state not reflected by the overall plasma immunoglobulin levels. Alternatively, these results could reflect a potential role of ubiquitous viruses in the pathogenesis of the disease. Further analyses are necessary to establish the relevance of such asymptomatic humoral immune responses against host viruses in the expansion of the tumor B-cell clone and progression from monoclonal B-cell lymphocytosis to CLL.
authors.affiliation: Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Criado
authors.affiliation: Microbiology Service, University Hospital of Salamanca, Spain.
authors.forename: Santiago
authors.initials: S
authors.lastname: Muñoz-Criado
authors.affiliation: Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
authors.forename: Arancha
authors.initials: A
authors.lastname: Rodríguez-Caballero
authors.affiliation: Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
authors.forename: Wendy G
authors.initials: WG
authors.lastname: Nieto
authors.affiliation: Gerencia de Atención Primaria de Salud, Centro de Atención Primaria de Salud Miguel Armijo, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Romero
authors.affiliation: Centro de Atención Primaria de Salud de Ledesma, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
authors.forename: Paulino
authors.initials: P
authors.lastname: Fernández-Navarro
authors.affiliation: Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL and Department of Medicine, University of Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Alcoceba
authors.affiliation: Biochemistry Service, University Hospital of Salamanca, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Contreras
authors.affiliation: Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL and Department of Medicine, University of Salamanca, Spain.
authors.forename: Marcos
authors.initials: M
authors.lastname: González
authors.affiliation: Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain. orfao@usal.es.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers; D018450:Disease Progression; D005260:Female; D054884:Host-Pathogen Interactions / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D016130:Immunophenotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D018655:Lymphocyte Count; D008218:Lymphocytosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014780:Viruses / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015415:Biomarkers; D007074:Immunoglobulin G; D007075:Immunoglobulin M