Altered Distribution of Peripheral Blood Maturation-Associated B-Cell Subsets in Chronic Alcoholism

摘要

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, na飗e, 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 na飗e B cells. AWLD showed reduced numbers of immature and na飗e 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 na飗e B cells, together with an increase in Ig-switched memory B lymphocytes and plasmablasts, particularly of IgA+ cells.