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Abstract: SA-PO979

Circulating Hypo-Sialylated IgM by FSGS Subjects Induce Proteinuria and Podocyte Injury

Session Information

Category: Glomerular Diseases

  • 1403 Podocyte Biology

Authors

  • Angeletti, Andrea, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Bruschi, Maurizio, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Candiano, Giovanni, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Kajana, Xhuliana, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Lugani, Francesca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Verrina, Enrico E., Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Caridi, Gianluca, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Spinelli, Sonia, Istituto Giannina Gaslini, Genova, Liguria, Italy
  • Ghiggeri, Gian Marco, Istituto Giannina Gaslini, Genova, Liguria, Italy
Background

Sialylation is an important regulator of protein function. Previous data showed that sialylation of total circulating IgM in Idiopathic Nephrotic Syndrome is significantly reduced compared to healthy subjects. The role of hiposialylated-IgM (hIgM) on podocytes in FSGS pathogenesis is unknown.

Methods

We characterized IgM derived by patients affected by multi-drug resistant FSGS (defined as lack of antiproteinuric effect of a double therapy based on steroid plus CNI and MMF for at least 12 months before enrolment). IgM were first analysed through two-dimensional electrophoresis. Sialylation levels were measured in total circulating IgM through incubation with biotinylated Sambucus nigra agglutinin (SNA). Then, sialylated and hyposialylated-IgM were put in culture with human podocytes. Incubation of podocytes with medium was used as control. IgM purified from serum of a patient were injected in rats.

Results

We enrolled 10 patients with resistant FSGS and 5 healthy controls, matched for age and sex (Fig1a). IgM derived from FSGS subjects induced significantly higher proteinuria than IgM from HC when injected in rats (Fig1b). IgM purified from serum of FSGS patients resulted significantly more cationic than IgM of HC (Fig1c), and as previously demonstrated, IgM cationic charge derived by hyposialylation (Fig1d). Co-incubation with hIgM, significantly induced human podocytes damage as opposed to sialylated IgM, which had no injurious effect (Fig1e).

Conclusion

Pathophysiology of FSGS is still largely unknown and common treatments often result poorly effective. We here reported that sialylation of IgM may be of relevance in this context, showing that hIgM induce in vivo proteinuria and in vitro podocytes structural damage. Therefore, hIgM may represent a promising therapeutic target for FSGS.