title: Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism.
abstract: BACKGROUND
  Although decreased counts of peripheral blood (PB) B cells-associated with an apparently contradictory polyclonal hypergammaglobulinemia-have been reported in chronic alcoholism, no information exists about the specific subsets of circulating B cells altered and their relationship with antibody production. Here, we analyzed for the first time the distribution of multiple maturation-associated subpopulations of PB B cells in alcoholism and its potential relationship with the onset of liver disease.
  
  
  METHODS
  PB samples from 35 male patients-20 had alcoholic hepatitis (AH) and 15 chronic alcoholism without liver disease (AWLD)-were studied, in parallel to 19 male healthy donors (controls). The distribution of PB B-cell subsets (immature/regulatory, naïve, CD27(-) and CD27(+) memory B lymphocytes, and circulating plasmablasts of distinct immunoglobulin-Ig-isotypes) was analyzed by flow cytometry.
  
  
  RESULTS
  Patients with AH showed significantly decreased numbers of total PB B lymphocytes (vs. controls and AWLD), at the expense of immature, memory, and, to a lesser extent, also naïve B cells. AWLD showed reduced numbers of immature and naïve B cells (vs. controls), but higher PB counts of plasmablasts (vs. the other 2 groups). Although PB memory B cells were reduced among the patients, the percentage of surface (s)IgA(+) cells (particularly CD27(-) /sIgA(+) cells) was increased in AH, whereas both sIgG(+) and sIgA(+) memory B cells were significantly overrepresented in AWLD versus healthy donors. Regarding circulating plasmablasts, patients with AH only showed significantly reduced counts of sIgG(+) cells versus controls. In contrast, the proportion of both sIgA(+) and sIgG(+) plasmablasts-from all plasmablasts-was reduced in AH and increased in AWLD (vs. the other 2 groups).
  
  
  CONCLUSIONS
  AH and AWLD patients display a significantly reduced PB B-cell count, at the expense of decreased numbers of recently produced immature/regulatory B cells and naïve B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA(+) cells.
authors.affiliation: Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer/IBMCC (CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), Cytometry Service, Salamanca, Spain.|Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.|Department of Medicine, IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Polvorosa
authors.affiliation: Department of Internal Medicine, University Hospital of Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Arturo
authors.initials: A
authors.lastname: Gonzalez-Quintela
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.|Department of Medicine, IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Madruga
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.|Department of Medicine, IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Marcos
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.|Department of Medicine, IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: Maria Angeles
authors.initials: MA
authors.lastname: Pérez-Nieto
authors.affiliation: Department of Clinical Biochemistry, University Hospital of Salamanca, Salamanca, Spain.
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Hernandez-Cerceño
authors.affiliation: Instituto de Biologia Molecular y Celular del Cancer, Centro de Investigacion del Cancer/IBMCC (CSIC-USAL), Institute of Biomedical Research of Salamanca (IBSAL), Cytometry Service, Salamanca, Spain.|Department of Medicine, University of Salamanca, Salamanca, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.affiliation: Alcoholism Unit, Department of Internal Medicine, University Hospital of Salamanca, Salamanca, Spain.|Department of Medicine, IBSAL, University of Salamanca, Salamanca, Spain.
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Laso
mesh_terms: D000437:Alcoholism / Q000097:blood* / Q000175:diagnosis*; D016175:B-Lymphocyte Subsets / Q000378:metabolism*; D006519:Hepatitis, Alcoholic / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male
keywords: Alcoholic Hepatitis; Bregs; Chronic Alcoholism; Circulating PB B-Cell Subsets; Liver Disease