Supplementary Material for: Glucocorticoids Reduce Aberrant O-Glycosylation of IgA1 in IgA Nephropathy Patients

<b><i>Background/Aims:</i></b> IgA nephropathy is associated with aberrant <i>O</i>-glycosylation of IgA1, which is recognized by autoantibodies leading to the formation of circulating immune complexes. Some of them, after deposition into kidney mesangium, trigger glomerular injury. In patients with active disease nonresponding to angiotensin-converting enzyme inhibitors or angiotensin II blockers, corticosteroids are recommended. <b><i>Methods:</i></b> The relationship between the corticosteroid therapy and serum levels of IgA, aberrantly <i>O</i>-glycosylated IgA1, IgA-containing immune complexes and their mesangioproliferative activity was analyzed in IgA nephropathy patients and disease and healthy controls. <b><i>Results:</i></b> Prednisone therapy significantly reduced proteinuria and levels of serum IgA, galactose-deficient IgA1, and IgA-IgG immune complexes in IgA nephropathy patients and thus reduced differences in all of the above parameters between IgAN patients and control groups. A moderate but not significant reduction of mesangioproliferative potential of IgA-IgG immune complexes and IgA sialylation was detected. <b><i>Conclusion:</i></b> The prednisone therapy reduces overall aberrancy in IgA1 <i>O</i>-glycosylation in IgA nephropathy patients, but the measurement of IgA1 parameters does not allow us to predict the prednisone therapy outcome in individual patients

The Resistance to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia: An Overview

The introduction in the clinical practice during the last decade of the tyrosine kinase inhibitors (TKI) have signifi cantly improved the outcome of patients affected by chronic myeloid leukemia (CML). Nevertheless, about one third of them still must stop or change treatment because of toxicity or resistance. Resistance could be “primary”, when patients don’t reach the established goals at the fi xed timepoints (see ELN or NCCN guidelines), or “secondary”, when patients lose the previously achieved hematological, cytogenetic or molecular response. At the basis of resistance many different mechanisms can be considered: the ABL1 mutations (rare at diagnosis but increasing at the progression, especially the T315I), the chromosomal adjunctive aberrations, but also the activation of other pathways able to sustain the growth of the progenitor leukemic stem cell, such as the Wnt, catenin, Scr, PI3K, and Hedgehog pathways. Moreover, also the epigenetic control of disease must be considered as a cause of resistance (such as that exerted by the Polycomb family). Finally, TKIs are often substrates of different transmembrane transporters; their polymorphisms and expression would explain either their possible lower effi cacy or higher toxicities. All these causes of resistance to TKIs are discussed in this paper