Normal range for acid-labile subunit in paediatric patients in Spain and its association with age, sex, pubertal stage and other growth factors.

INTRODUCTION: The acid-labile subunit (ALS) plays an important role in the endocrine effects of insulin-like growth factors (IGFs) on target tissues. Historically, it has attracted limited attention. The aim of our study was to describe the normal range of ALS in healthy children and its association with other growth factors. PATIENTS AND METHODS: We designed a cross-sectional descriptive study. We collected data on age, height, body mass index, gestational age, anthropometry at birth and serum levels of ALS, IGF1 and IGFBP3 in healthy children aged 2-15 years with a normal height. The levels of ALS, IGF1 and IGFBP3 were measured by ELISA. We fitted GAMLSS normalization models to standardize the variables. RESULTS: Samples were collected from 446 children. In prepubertal children, the levels of ALS, IGF1 and IGFBP3 were positively correlated in both sexes and with age (P < .01). We found significant differences in the levels of ALS, IGF1 and IGFBP3 and the IGF1/IGFBP3 molar ratio between the sexes and higher levels in pubertal boys (P < .01). We generated normal probability plots for each sex for each of the components of the ternary complex and for the IGF1/IGFBP3 and IGFBP3/ALS molar ratios. In addition, we extracted equations from the models for the calculation of z-scores for age and sex. CONCLUSIONS: This study may contribute age- and sex-specific reference values for IGF1, IGFBP3 and ALS levels and IGF1/IGFBP3 and IGFBP3/ALS ratios in Spanish children and suggests an association between age, sex, and pubertal stage.

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.

Decreased peripheral blood CD4+/CD25+ regulatory T cells in patients with alcoholic hepatitis.

BACKGROUND: Development of alcoholic hepatitis (AH) may be favored by the activation of the innate immune response. Recently, decreased numbers of circulating regulatory T cells (Tregs) have been reported in diseases associated with an immune activation status, but no studies have focused so far, in investigating the distribution of Tregs in chronic alcoholism and its potential association with liver disease. Here, we analyzed for the first time the frequency of peripheral blood (PB) Tregs and Treg subsets in AH and its relationship with the production of inflammatory cytokines by PB monocytes and dendritic cells (DCs). METHODS: PB samples from 25 male patients with AH were studied; in parallel, 15 male chronic alcoholic patients without liver disease (AWLD) and 17 male healthy donors were also studied, as controls. The distribution of CD4⁺CD25hiCD127-/lo Tregs and their maturation subsets (naïve, central memory, and peripheral memory Tregs) was analyzed by flow cytometry. Spontaneous and in vitro-stimulated production of inflammatory cytokines by PB monocytes and DCs was analyzed by flow cytometry at the cytoplasmic level. RESULTS: Patients with AH showed decreased (p < 0.05) numbers of PB CD4⁺CD25hiCD127-/lo Tregs at the expense of all maturation-associated subsets, while AWLD and healthy subjects showed a similar (p > 0.05) distribution of PB CD4⁺CD25hiCD127-/lo Tregs. Interestingly, significantly increased amounts of spontaneously produced inflammatory cytokines were found among circulating monocyte-derived DCs and monocytes from AH (and AWLD) patients in comparison with healthy donors. Conversely, the ability of these cell subsets to produce cytokines after in vitro stimulation was lower (p < 0.05) in AH versus the 2 control groups. CONCLUSIONS: PB CD4⁺CD25hiCD127-/lo Tregs are significantly decreased in patients with AH when compared to both healthy and AWLD; this may contribute to explain the more pronounced activation of the innate immune response observed in AH, as reflected by an increased secretion of inflammatory cytokines by PB DCs and monocytes, and could facilitate the development of liver disease.