The role of the immune system in idiopathic nephrotic syndrome: a review of clinical and experimental studies

Abstract

Idiopathic nephrotic syndrome (INS) is a multifactorial disease, characterized by proteinuria, hypoalbuminemia, edema and hyperlipidemia. Studies in humans and animal models have associated INS with changes in the immune response. The purpose of this article is to review clinical and experimental findings showing the involvement of the immune response in the pathogenesis of INS. The role of the immune system in INS has been shown by clinical and experimental studies. However, the pattern of immune response in patients with INS is still not clearly defined. Many studies show changes in the dynamics of T lymphocytes, especially the regulatory T cells. Alternatively, there are other reports regarding the involvement of the complement system and B lymphocytes in the pathophysiology of INS. Indeed, none of the immunological biomarkers evaluated were undeniably linked to changes in glomerular permeability and proteinuria. On the other hand, some studies suggest a link between urinary chemokines, such as IL-8/CXCL8 and MCP-1/CCL2, and changes in glomerular permeability and/or the deterioration of glomerulopathies. To understand the pathophysiology of INS, longitudinal studies are clearly needed. The characterization of the profile of the immune response might help the development of specific and individualized therapies, leading to clinical improvement and better prognosis.

Induction of C-Mip by IL-17 Plays an Important Role in Adriamycin-Induced Podocyte Damage

“…It was reported that the severity of NS is associated with the decreased activity of Treg cells [9,11,12]. Similar finding showed that peripheral blood mononuclear cells (PBMC) of children with NS exhibited a reduction in Treg cells that is in parallel to an increase in Th17 cells [13].…”

“…Similar finding showed that peripheral blood mononuclear cells (PBMC) of children with NS exhibited a reduction in Treg cells that is in parallel to an increase in Th17 cells [13]. Treg cells have an anti-inflammatory role and maintain tolerance to self-components through direct contact with cells or by releasing anti-inflammatory cytokines such as IL-10 and TGF-β [9,14]. Nevertheless, Th17 cells play a key role in induction of autoimmune tissue injuries and inflammation by releasing IL-17 [15].…”

“…Studies in humans and animal models have shown that the pathogenesis of idiopathic NS is associated with changes in the immune responses, such as the abnormal response of T lymphocytes and the increased production of local cytokine release [9,23]. It is still unclear whether there is a potential relationship between T lymphocyte abnormality and glomerular podocyte injury, and whether there is a putative factor produced by immune cells that can alter podocyte function leading to nephrotic proteinuria.…”

“…The induction of c-mip and B7-1 in both lymphocytes and podocytes provides further evidence that there may be some relationship between lymphocyte and podocyte in MCNS. Early in 1970s, it was proposed that MCNS is a disorder of lymphocyte function with increased levels of lymphocyte-released cytokines, which could induce podocyte injury and thus increase glomerular permeability to plasma proteins [9]. Although the findings of disturbance of both lymphocyte and glomerular podocyte in the disease suggest that a putative factor produced by immune cells may alter podocyte function leading to nephrotic proteinuria, the mechanism underlying the pathophysiology of podocyte damage and proteinuria development is still not understood very well.…”

The Correlation of Regulatory T (TReg) and Vitamin D3 in Pediatric Nephrotic Syndrome

“…Conversely, regulatory T-cells (T Reg ) is an important tolerogenic T-cell possessing protective effect on podocyte destruction [6,7]. Vitamin D has been known as immunomodulator that able to induce T Reg differentiation as it has pleiotropic effects [8,9].…”