Altered distribution of peripheral blood maturation-associated B-cell subsets in chronic alcoholism

[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.This study was supported by the Plan Nacional sobre Drogas, grant number 2007/020 to F-J. L., Ministerio de Sanidad y Consumo, Madrid, Spain and the Red de Trastornos Adictivos of Instituto de Salud Carlos III—FONDOS FEDER with expedient numbers RD06/0001/0004 and RD12/0028/0008 to FJL.Peer Reviewe