Atypical IgM on T cells predict relapse and steroid dependence in idiopathic nephrotic syndrome.

The clinical heterogeneity of idiopathic nephrotic syndrome in childhood may reflect different mechanisms of disease that are as yet unclear. Here, we evaluated the association between an atypical presence of IgM on the surface of T cells (T-cell IgM) and the response to steroid therapy in a total of 153 pediatric patients with idiopathic nephrotic syndrome in different phases of disease. At disease onset, T-cell IgM median levels were significantly elevated and predictive of risk of relapse in 47 patients. They were also significantly increased comparing 58 steroid-dependent to 8 infrequently relapsing and 14 frequently relapsing patients, especially during relapse, whereas they were within the normal range in 7 genetic steroid-resistant patients. T-cell IgM in vivo was not affected by the amount of total circulating IgM, nor by concomitant acute infections or oral immunosuppression. However, it was affected by rituximab treatment in 21 steroid-dependent patients. By in vitro experiments, elevated T-cell IgM was not influenced by total circulating IgM levels or by the presence of other circulating factors, and there was no distinctive antigen-specificity or atypical IgM polymerization. Rather, we found that increased T-cell IgM correlates with reduced IgM sialylation, which influences T-cell response to steroid inhibition and T-cell production of podocyte-damaging factors. Thus, the atypical presence of IgM on the surface of T cells may predispose a subset of steroid-sensitive pediatric patients with idiopathic nephrotic syndrome to a poor response to steroid therapy since disease onset.

Immunology of idiopathic nephrotic syndrome.

The pathogenesis of idiopathic nephrotic syndrome (INS) is as yet unknown, but several lines of evidence indicate that the immune system may play a crucial pathogenic role in non-genetic INS. The most important of these are, first, the effectiveness of therapy based on immunosuppression and, second, a vast body of data derived both from experimental models and from patient studies that implicate T cells and more recently B cells as major players in INS pathogenesis. However, recent findings also suggest a direct role of podocytes as drivers of the disease process, and the interplay between the glomerulus and the immune system is still being elucidated. In this review we provide an overview of current knowledge on the role of different components of the immune system in determining disease. Advances in our understanding of the pathogenesis of INS may help drive new, more tailored therapeutic approaches.

A modified procedure based on a vacuum-driven blotting system for the detection of erythropoietin and its analogs.

BACKGROUND: The intake of erythropoietins as performance-enhancing drugs is banned in sport. The current method for their detection is based on advanced electrophoretic techniques (IEF-PAGE and SDS-PAGE/sarcosyl-PAGE) with double-blotting and chemiluminescence detection, requiring at least 2.5 days to be completed. Methodology & Results: The proposed procedure, based on vacuum-driven blotting technology, drastically reduces the time necessary to complete the analysis, while still fulfilling the criteria of the World Anti-Doping Agency. Validation was carried out on urine samples spiked with different recombinant erythropoietins, as well as on urine samples obtained following controlled excretion studies and on anonymized urine samples from antidoping tests. CONCLUSION: The proposed approach, allowing a faster turnaround time, could be very advantageous on the occasion of major sport international events (i.e., Olympic Games).