Role of the immune system in the pathogenesis of idiopathic nephrotic syndrome

Abstract

Idiopathic NS (nephrotic syndrome) is characterized by massive proteinuria, due to a leak in the glomerular barrier to proteins. Genetic defects that affect the function and the composition of the glomerular capillary wall, in particular of the visceral epithelial cells, have recently been recognized as the cause of familial forms of NS. MCNS (minimal change NS) and FSGS (focal and segmental glomerulosclerosis) are common non-familial forms of NS in which the causative defect has not yet been identified. Several studies have shown that non-familial NS is associated with the presence of circulating permeability factors and with complex disturbances in the immune system. Thus far, there is no direct evidence that these factors directly alter glomerular permeability to proteins, and some of these factors may be a consequence, rather than a cause, of NS. In this review, we will briefly highlight the mechanisms that underlie proteinuria in general and focus on the immunological disturbances associated with idiopathic NS, with attention to potential mechanisms whereby the immune system may directly act on the glomerular capillary filter.

Immune Mediators in Idiopathic Nephrotic Syndrome: Evidence for a Relation Between Interleukin 8 and Proteinuria

“…In 1974, Shalhoub (25) developed a hypothesis that INS was an immune disorder, with increased levels of a lymphocyte-derived permeability factor. Since then, several groups have studied possible factors that could be responsible, at least in part, for the physiologic abnormalities of INS (4,26). In this study, we specifically focused on the evaluation of blood and urinary concentrations of TGF-␤ 1 , MCP-1/CCL2, RANTES/CCL5 and IL-8/CXCL8 in children with INS, since previous reports described alterations of these immune mediators in diverse renal diseases, including glomerulopathies (8,12,15,19,27).…”

“…Cytokines are a group of proteins produced by several kinds of cells that function as soluble mediators with intercellular signaling functions (4). Chemokines constitute a large family of lowmolecular-weight cytokines whose main action is the recruitment and activation of leukocyte subsets in various models of inflammation-the word "chemokine" is a contraction of the terms "chemoattractant" and "cytokine" (9,10).…”

MicroRNAs in Idiopathic Childhood Nephrotic Syndrome

“…Dysregulation of the immune system, particularly cellular immunity, has been shown to be involved in idiopathic NS (14 ). miR-150, which is produced in lymph nodes, is associated with the maturation of functional T cells and B cells (15 ).…”

Blood T-Cell Repertoire in Idiopathic Nephrotic Syndrome Recurrence Following Kidney Transplantation

“…The predominant form of INS is an 'immunologic' form where the role of a circulating factor or factors, whose production seems to follow T-cell dysfunction, has been suggested for more than three decades (11). Most of experimental studies have focused on the role of T lymphocytes in the progression of corticosteroid-sensitive INS (12) and have tried to make a link between these cells and the putative circulating factor. Using a subtractive cDNA library screening technique on peripheral blood mononuclear cells (PBMC), Sahali et al showed a down regulation of the IL12-R b2 mRNA subunit and an upregulation of c-maf during relapse compared with MCNS patients in remission (13).…”