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Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression
Ignacio Criado, Santiago Muñoz-Criado, Arancha Rodríguez-Caballero, Wendy G. Nieto, Alfonso Romero, Paulino Fernández-Navarro, Miguel Alcoceba, Teresa Contreras, Marcos González, Alberto Orfao, Julia Almeida
Haematologica July 2017 102: 1238-1246; doi:10.3324/haematol.2016.159012
Ignacio Criado
Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
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Santiago Muñoz-Criado
Microbiology Service, University Hospital of Salamanca, Spain.
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Arancha Rodríguez-Caballero
Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
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Wendy G. Nieto
Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
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Alfonso Romero
Gerencia de Atención Primaria de Salud, Centro de Atención Primaria de Salud Miguel Armijo, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
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Paulino Fernández-Navarro
Centro de Atención Primaria de Salud de Ledesma, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
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Miguel Alcoceba
Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL and Department of Medicine, University of Salamanca, Spain.
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Teresa Contreras
Biochemistry Service, University Hospital of Salamanca, Spain.
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Marcos González
Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL and Department of Medicine, University of Salamanca, Spain.
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Alberto Orfao
Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
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  • For correspondence: orfao@usal.es
Julia Almeida
Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
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Author Affiliations

  1. Ignacio Criado1,
  2. Santiago Muñoz-Criado2,
  3. Arancha Rodríguez-Caballero1,
  4. Wendy G. Nieto1,
  5. Alfonso Romero3,
  6. Paulino Fernández-Navarro4,
  7. Miguel Alcoceba5,
  8. Teresa Contreras6,
  9. Marcos González5,
  10. Alberto Orfao1⇑ and
  11. Julia Almeida1
  12. The Primary Health Care Group of Salamanca for the Study of MBL
  1. 1Cancer Research Centre (IBMCC, USAL-CSIC), Department of Medicine and Cytometry Service (NUCLEUS), University of Salamanca and IBSAL, Salamanca, Spain.
  2. 2Microbiology Service, University Hospital of Salamanca, Spain.
  3. 3Gerencia de Atención Primaria de Salud, Centro de Atención Primaria de Salud Miguel Armijo, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
  4. 4Centro de Atención Primaria de Salud de Ledesma, Salamanca, Sanidad de Castilla y León (SACYL), Spain.
  5. 5Hematology Service, University Hospital of Salamanca, IBMCC, IBSAL and Department of Medicine, University of Salamanca, Spain.
  6. 6Biochemistry Service, University Hospital of Salamanca, Spain.
  1. Correspondence:
    orfao{at}usal.es
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Data supplements

  • Criado et al. Supplementary Appendix

    Criado et al. Supplementary appendix provided by the authors.

    Files in this Data Supplement:

    • Adobe PDF - 2016.159012.CRIADO_SUPPL.pdf
  • Disclosures and Contributions

    Files in this Data Supplement:

    • Adobe PDF - 2016_159012-Disclosures_and_Contributions.pdf

ARTICLE FIGURES & DATA

Figures

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  • Figure 1.
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    Figure 1.

    Soluble immunoglobulin immunoglobulin (Ig) plasma levels in monoclonal B lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) versus healthy donors. (A) The overall amount of plasma immunoglobulins (md/dl) determined by conventional nephelometry is shown for the different groups of individuals analyzed. (B–D) IgM, IgG and IgA plasma levels within the different groups of individuals studied, respectively. Notched boxes represent 25th and 75th percentile values; the lines in the middle correspond to median values (50th percentile) and vertical lines represent the highest and lowest values that are neither outliers nor extreme values. Vertical dotted lines represent the inferior limit value of normality for each immunoglobulin. Dotted lines represent the lower limit of normality for each immunoglobulin (40 mg/dl; 700 mg/dl; and 70 mg/dl). Numbers under dotted lines represent the percentage of cases with plasma levels of the corresponding immunoglobulin found to be below normal values. *P<0.05 versus healthy donors and MBLlo; **P<0.05 versus healthy donors, MBLlo and MBLhi. MBLhi: high-count monoclonal B lymphocytosis; MBLlo: low-count monoclonal B lymphocytosis.

  • Figure 2.
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    Figure 2.

    Ratio between pathogen-specific immunoglobulin (Ig) plasma levels and total immunoglobulin plasma levels per Ig isotype in monoclonal B lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) patients versus healthy subjects. (A and B) Ratio between cytomegalovirus (CMV)-specific IgM and IgG plasma titers and the overall plasma IgM and IgG levels, respectively. (C and D) Ratio between viral capside antigen (VCA)-Epstein-Barr virus (EBV)-specific IgM and IgG titers in plasma and the overall amount of IgM and IgG in plasma, respectively. (E) Anti Epstein-Barr nuclear antigen (EBNA)-EBV-specific IgG/total IgG plasma level ratio. (F and G) Influenza (strains A + B)-specific/total IgM and IgG ratios, respectively. Only data on seropositive subjects for each pathogen are included in this figure. (F and G) Data presented correspond only to subjects who referred no previous vaccination against influenza. Notched boxes represent 25th and 75th percentile values; the lines in the middle correspond to median values (50th percentile), whereas vertical lines represent the highest and lowest values that are neither outliers nor extreme values. *P<0.05 versus healthy donors and MBLlo; **P<0.05 versus healthy donors, MBLlo and MBLhi.

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    Figure 3.

    Streptococcus pneumoniae-specific IgG plasma levels in monoclonal B lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL) patients versus healthy controls. (A) Titers of antibody-specific plasma levels against the pneumococcal polysaccharide antigen for each group of individuals analyzed. (B) Ratio between anti-pneumococcus-specific IgG and total IgG plasma levels for each group of subjects investigated. Only data from those subjects that did not receive vaccination against S.pneumoniae are displayed. Notched boxes represent 25th and 75th percentile values; the lines in the middle correspond to median values (50th percentile), while vertical lines represent the highest and lowest values that are neither outliers nor extreme values. *P<0.05 versus healthy donors and MBLlo. MBLhi: high-count monoclonal B lymphocytosis; MBLlo: low-count monoclonal B lymphocytosis.

Tables

  • Figures
  • Table 1.

    Clinical and laboratory characteristics of controls versus monoclonal B-cell lymphocytosis subjects and chronic lymphocytic leukemia patients.

    Table 1.
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Vol 102 Issue 7

Haematologica: 102 (7)
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Host virus and pneumococcus-specific immune responses in high-count monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia: implications for disease progression
Ignacio Criado, Santiago Muñoz-Criado, Arancha Rodríguez-Caballero, Wendy G. Nieto, Alfonso Romero, Paulino Fernández-Navarro, Miguel Alcoceba, Teresa Contreras, Marcos González, Alberto Orfao, Julia Almeida
Haematologica Jul 2017, 102 (7) 1238-1246; DOI: 10.3324/haematol.2016.159012

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Ignacio Criado, Santiago Muñoz-Criado, Arancha Rodríguez-Caballero, Wendy G. Nieto, Alfonso Romero, Paulino Fernández-Navarro, Miguel Alcoceba, Teresa Contreras, Marcos González, Alberto Orfao, Julia Almeida
Haematologica Jul 2017, 102 (7) 1238-1246; DOI: 10.3324/haematol.2016.159012
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