High levels of soluble ST2 protein in recurrence of idiopathic nephrotic syndrome after kidney transplantation

After transplantation, corticosteroid-resistant Idiopathic Nephrotic Syndrome (INS) rapidly recurs in 30-50% of recipients, suggesting the presence of (a) circulating factor(s) which alter(s) the glomerular filtration barrier. In this paper, we investigated the possible implication of the soluble ST2 protein (sST2), a product of the c-maf pathway and a marker of Th2 cells, in the development of INS recurrence, as an association between INS relapse and an atypical Th2 polarization involving activation of c-maf has recently been reported. We analyzed sST2 levels in the serum of kidney recipients with INS as their primary kidney disease but with (n=31) and without (n=40) recurrence after transplantation and of recipients with primary glomerular diseases different from INS (n=34). We found a significant increase of sST2 levels in the sera of patients suffering INS recurrence, but not in those of non-recurrent INS and non-INS patients. No differences were detected in these sera before transplantation. Moreover, recurrent patients displayed the same sST2 isoform as the two control groups. In vitro, a mouse podocyte cell line was profoundly altered by incubation with sera of recurrent patients. However, purified sST2 from these patients was not able to reproduce these damages. In addition, induction of high sST2 levels in rats did not trigger proteinuria. Collectively, these data suggest that sST2 is a marker of INS recurrence that could be of interest for its diagnosis in ambiguous clinical situations. Nonetheless, sST2 does not seem to be directly implicated in INS development.