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Immunologic Mechanisms in Renal Disease
Published in Robin S. Goldstein, Mechanisms of Injury in Renal Disease and Toxicity, 2020
Brian D. Schreiber, Gerald C. Groggel
Deposits in the subepithelial space are characteristic of human membranous nephropathy. At this site, deposits are formed primarily if not entirely by in situ mechanisms (Couser, 1985). The antigen can be either an endogenous, insoluble glomerular antigen or an exogenous, soluble antigen which is deposited in the glomerulus on the basis of some physiochemical characteristic. In situ formation of immune deposits was initially identified in a rat model of human membranous nephropathy, Heymann nephritis (Couser et al., 1978). In this model, antibody interacts with an antigen on the membrane of the glomerular epithelial cell. The best characterized of these antigens is a glycoprotein, GP330, which has a molecular weight of 330 kD and is also found on the brush border of the renal proximal tubule (Kerjaschki and Farquhar, 1982, 1983). If rats are injected with this antigen in passive Heymann nephritis, they deposit complement fixing IgG and develop proteinuria over a period of 4 to 5 d (Salant et al., 1980a). The heterologous IgG and rat C3 stain in a granular pattern. Subepithelial electron dense deposits are seen by electron microscopy. It appears that once the immune complexes form on the epithelial cell membrane, patching and shedding of the immune complexes from the cell surface occurs (Camussi et al., 1985; Brentjens and Andres, 1989). This phenomenon most likely produces the finely granular appearance seen. The deposits may form on a local or in situ basis.
A preliminary nomogram model for predicting relapse of patients with primary membranous nephropathy
Published in Renal Failure, 2023
Min Li, Huifang Wang, Xiaoying Lai, Dandan Guo, Chunhui Jiang, Zixuan Fu, Xuemei Liu
A total of 983 adult patients diagnosed with membranous nephropathy (MN) by renal biopsy in the Affiliated Hospital of Qingdao University from January 2013 to May 2021 were enrolled and followed up. The exclusion criteria included: (1) Secondary membranous nephropathy caused by autoimmune diseases (lupus nephritis, purpura nephritis, etc.), hepatitis, malignancy, drugs and other systemic diseases; (2) MN combined with another primary or secondary glomerulonephritis (diabetic nephropathy, hypertensive nephropathy, etc.); (3) Patients treated with immunosuppressive agents or corticosteroids before renal biopsy; (4) Patients were not followed up or followed up irregularly. After rigorous screening, 395 MN patients were excluded. Patients with PMN were followed up for more than 6 months after achieving remission, the follow-up endpoint was 30 November 2021 or relapse. Finally, 400 patients were enrolled in our study, they were divided into development group and validation group according to a ratio of 7:3 randomly (Figure 1). This study was conducted following the Declaration of Helsinki and was approved by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University (the ethics approval number is QYFY WZLL 27505).
Mercury-associated neural epidermal growth factor-like 1 protein (NELL-1) positive membranous nephropathy after use of skin lightening creams
Published in Clinical Toxicology, 2023
Amar Sultan, Deepali Mamankar, Sayali Thakare, Amey Rojekar, Tukaram Jamale
Membranous nephropathy, a leading cause of nephrotic syndrome in adults, is often primary which is attributed to antibodies against various antigens of the glomerular podocytes [1]. Membranous nephropathy can also be secondary to autoimmune conditions, infections, malignancies and after exposure to drugs or toxins. Identification of various podocyte target antigens has improved the understanding of membranous nephropathy over the last decade [2]. Neural epidermal growth factor-like 1 protein (NELL-1) is one such recently identified target antigen and is described in association with malignancy, lipoic acid, and traditional Indian medicine use [2–4]. We report a series of patients with NELL-1 positive membranous nephropathy in association with mercury exposure from skin lightening cream.
Analysis of glomerular PLA2R efficacy in evaluating the prognosis of idiopathic membranous nephropathy in the background of different serum anti-PLA2R levels
Published in Renal Failure, 2022
Yuemeng Sun, Ping Lan, Jie Feng, Zhigang Wang, Chao Liu, Liyi Xie, Xiaoyang Yu
Membranous nephropathy (MN) is characterized by the deposition of immune complexes in the subepithelial space and the diffuse thickening of the glomerular basement membrane, which is now the leading cause of nephrotic syndrome in adults [1]. The M-type phospholipase A2 receptor (PLA2R), first discovered by Beck, which located on cell surface of podocytes, is the major auto-antigen in most patients with idiopathic membranous nephropathy (IMN) [2]. Previous studies mainly focused on the serum antibody status of patients with IMN. It is generally believed that the levels of antibody titer are correlated with disease severity and prognosis [3–5], in which higher titer predicted more severe proteinuria and less chance to remission. However, there are few studies on glomerular PLA2R antigen in evaluating the prognosis of the disease, especially the relationship between different levels of glomerular PLA2R antigen combined with serum PLA2R antibody and disease risk. Based on the stratification of serum PLA2R antibody levels, our study analyzed the different effects of glomerular PLA2R antigen on the prognosis assessment of IMN, and further explained how to evaluate the disease risk by combining glomerular PLA2R antigen and serum PLA2R antibody.