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Copetti V.,University of Trieste | Pastore S.,University of Trieste | Pastore S.,Institute of Maternal and Child Health IRCCS Burlo Garofolo | De Pieri C.,Institute of Maternal and Child Health IRCCS Burlo Garofolo | And 6 more authors.
Archives of Disease in Childhood: Education and Practice Edition | Year: 2014

The causes of extremely elevated IgA, whether isolated or associated with an increase in other classes of immunoglobulin, are poorly defined in paediatrics. We reviewed the diagnostic significance of very high IgA levels (greater than 3 SD above the mean for age) in a cohort of patients referred to a tertiary care children's hospital. Hyper-IgA was found in 91 of 6364 subjects (1.4%) and in 68 cases was not associated with an increased IgG and/or IgM level. Most subjects with hyper-IgA (73.5%) had a severe immune defect, a chronic rheumatic disease or inflammatory bowel disease, while these conditions were very rare in a control group with normal IgA values (8%). Although our results may in part reflect the experience of a tertiary care centre, we suggest that hyper-IgA in children should always arouse suspicion of a serious disease.

Valencic E.,Institute of Maternal and Child Health IRCCS Burlo Garofolo | Loganes C.,Institute of Maternal and Child Health IRCCS Burlo Garofolo | Cesana S.,University of Milan Bicocca | Cesana S.,San Gerardo Hospital | And 6 more authors.
Stem Cell Research and Therapy | Year: 2014

Introduction. Despite having a proven immunosuppressive potential in vitro, human mesenchymal stromal cells (MSCs) are reported to display variable efficacy in vivo and, in fact, their proven benefit in the clinical practice is still limited and controversial. Methods. The interplay between clinical grade MSCs and pre-activated donor lymphocytes or selected lymphocyte subsets was studied in vitro. The kinetics of MSC growth and viability was evaluated by adhesion-dependent changes of culture plate impedance and biochemically by a colorimetric assay. Activation of natural killer (NK) cells was assessed as well, using a flow cytometry assay. Results: A strong inhibition of MSC growth was rapidly induced by the addition of pre-activated lymphocytes but not of resting lymphocytes. Inhibition seems not to be attributable to a single cell population, as similar results can be obtained by depleting NK cells or by using either selected CD4§ssup§+§esup§ or CD8§ssup§ +§esup§ lymphocytes. In addition, conditioned medium (CM) from activated lymphocytes was able to inhibit MSC growth in a dose-dependent manner. Furthermore, licensing with IFN-γ partially protected MSCs from pre-activated lymphocytes but not from their CM. These results suggest an inhibitory role of lymphocyte-activation-derived substances. However, the identification of a single molecule responsible for MSC inhibition remained elusive, even if preliminary experiments showed that ATP and, to a lesser extent, TNF- might play a role. Conclusions: These results suggest that survival of MSCs can be affected by soluble mediators released by activated lymphocytes. Thus it can be hypothesized that MSC immunosuppressive action in vivo could be impaired by ongoing immune activation through the release of inflammatory mediators. © 2014 Valencic et al.; licensee BioMed Central Ltd.

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