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Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

The potential benefit of interferon (IFN)-alpha therapy in early-stage B cell chronic lymphocytic leukemia (B-CLL) patients is still under discussion, and no assays are available to distinguish potential responders from nonresponders. Herein we analyzed the usefulness of serum tumor necrosis factor (TNF, a cytokine released by CLL cells) and MxA protein (an intracellular marker for biologic activity of endogenous IFN) concentrations as predictive measurements for evolution and response to IFN therapy in early-stage CLL patients. TNF levels and MxA expression were determined at diagnosis in 21 CLL patients. A statistically significant correlation was found between low TNF levels and MxA expression and between high TNF levels and no measurable MxA expression. The patients were then randomized to receive IFN-alpha or no therapy and were evaluated for response and evolution. When response to IFN-alpha therapy was considered, it became apparent that early-stage CLL patients with higher TNF levels and no measurable MxA expression were more likely to benefit from IFN therapy, whereas those patients with lower TNF levels and MxA expression could be considered CLL candidates for longer survival without therapy. More patients have to be tested to strengthen the value of MxA expression and TNF concentrations for subsequent response to IFN-alpha therapy.

Abstract. One of the largest challenges with soil information around the world is how to harmonize archived soil data from different sources and how to make it accessible to soil scientist. In Ecuador, there have been two major projects that have provided soil information, but the methodology of these projects, although comparable, did not coincide, especially with respect to how information was reported. Here, we present a new soil database for Ecuador, comprising 13 542 soil profiles with 51 713 measured soil horizons, including 92 different edaphic variables. The original data were in a non-editable format (i.e., PDF), which made it difficult to access and process the information. Our study provides an integrated framework that combines multiple analytic tools for automatically converting legacy soil information from an analog format into usable digital soil mapping inputs across Ecuador. This framework allowed us to incorporate quantitative information on a broad set of soil properties and retrieve qualitative information on soil morphological properties collected in the profile description phase, which is rarely included in soil databases. We present a new harmonized national soil database using a specific methodology to preserve relevant information. The national representativeness of soil information has been enhanced compared with other international databases, and this new database contributes to filling the gaps in publicly available soil information across the country. The database is freely available at https://doi.org/10.6073/pasta/1560e803953c839e7aedef78ff7d3f6c (Armas et al., 2022).