About this Research Topic
Nephrotic syndrome is a multifactorial disease characterized by massive proteinuria and hypoalbuminemia. Nephrotic syndrome is usually dichotomized either as idiopathic nephrotic syndrome - which is referred to as minimal change disease (MCD), and focal and segmental glomerulosclerosis (FSGS) - and membranous nephropathy (MN). Idiopathic nephrotic syndrome is the most frequent glomerular disease in childhood while MN remains the first etiology in non-diabetic adult nephrotic syndrome. Studies in human and animal models have shown the association of nephrotic syndrome with the impairment of the immune response. The effectiveness of therapy based on immunosuppression strongly implicates the immune system in nephrotic syndrome pathogenesis. However, the pattern of immune response in patients with nephrotic syndrome remains unclear.
Recent reports described a direct role for podocytes as drivers of the disease process. Non-genetic idiopathic nephrotic syndrome pathophysiology includes a complex interplay between circulating proteins (circulating permeability factors), immune system and podocytes. Trigger events (e.g. infections, vaccination or allergens) can stimulate antigen-presenting cells and B cells. Then, B cells can activate T cells by antigen presentation and the production of cytokines. Changes in dynamics of T lymphocytes have been described in idiopathic nephrotic syndrome: an imbalance between Th2 and Th1 cells and reduced function of regulatory T cells (Treg) opposed to an increase of Th17 cells activity. B cell activation has also been observed: increased release of the soluble form of CD23, a correlation between memory B cells recovery and relapse after rituximab therapy and the presence of anti-CD40 autoantibodies. In addition to the production of cytokines and autoantibodies, other circulating permeability proteins can directly affect podocytes, leading to foot process effacement and disruption of the glomerular permeability barrier. Furthermore, podocytes can also sense microbial products by specific toll-like receptors and express costimulatory molecules such as CD40 which are able to induce T cells activation.
Membranous nephropathy is caused by the formation of immune complexes in the space between podocytes and the glomerular basement membrane. In idiopathic MN, immune complexes are formed by circulating antibodies binding to podocytes antigens: M-type phospholipase A2 receptor (PLA2R1) in 70% of patients, thrombospondin type-1 domain containing 7A (THSD7A) in 2% to 5% of patients or NELL-1 in 2% to 7% of patients. However, the mechanism of anti-podocyte antibody production in MN remains unclear. Genetic factors have been described, but immune triggers and immune dysfunction of T cells inducing breaking immune tolerance are not yet well characterized. As in idiopathic nephrotic syndrome, an imbalance between Th17 and Treg has recently been reported in MN associated with thrombosis and relapsing MN. Proteinuria in MN probably results of podocyte injury and complement activation. Idiopathic nephrotic syndrome and idiopathic MN respond to immunosuppressive regimens, This also highlights the implication of the immune system.
This Research Topic will address the most recent updates on the immune system dysregulation in idiopathic nephrotic syndrome (i.e. MCD and FSGS) and idiopathic membranous nephropathy, shedding light on immunological pathogenesis of these diseases and try to provide potential novel therapeutic targets for nephrotic syndrome.
We welcome manuscripts focusing on, but not limited to, the following areas:
• Pathophysiology mechanisms in nephrotic syndrome and its complications
• Immune mechanisms involved in secondary nephrotic syndrome
• Immune biomarkers and monitoring in nephrotic syndrome
• Factors predicting relapses and non-response to first-line therapy
• New therapeutic targets in nephrotic syndrome
Keywords: nephropathy, autoantibodies, complement, Immune dysfunction in nephrotic syndrome
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