Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity

Liu, Wenbin; Gao, Chang; Liu, Zhiyuan; Dai, Haoran; Feng, Zhendong; Dong, Zhaocheng; Zheng, Yang; Gao, Yu; Tian, Xuefei; Liu, Baoli

doi:10.3389/fimmu.2020.01846

Cited by 30 publications

(24 citation statements)

References 119 publications

(158 reference statements)

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“…Th17 cells in IMN have been a heated topic recently, and studies from different research groups suggested the up-regulation of Th17 and the increase of IL-6 and IL-17A. This indicates that IMN is conducive to Th17 cells differentiation, and also strengthens our confidence that IMN is originated from extrarenal inflammation (115). Increased Th17 cells are also associated with a higher recurrence rate and a higher risk of venous thrombosis (71), which is a concern for clinical treatment.…”

Section: Th Cells Involved In the Immune Dysregulation Of Imnmentioning

confidence: 78%

“…Cellular immune-mediated diseases are usually infiltrated by local monocytes and cytotoxic T cells. Although IMN presents as an organ-specific autoimmune disease, there is a local lack of cell infiltration that mediates cellular immunity in the glomerulus, and the generation of proteinuria may be caused by antibody activation of complement that damages the podocytes or antibody affecting podocyte function (115)(116)(117). The predictive value of anti-PLA2R antibody titers for clinical prognosis has also been vigorously described (69).…”

Section: Th Cells Involved In the Immune Dysregulation Of Imnmentioning

confidence: 99%

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Helper T Cells in Idiopathic Membranous Nephropathy

et al. 2021

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Idiopathic membranous nephropathy (IMN) is an autoimmune disease in which the immune system produces an antibody response to its own antigens due to impaired immune tolerance. Although antibodies are derived from plasma cells differentiated by B cells, the T-B cells also contribute a lot to the immune system. In particular, the subsets of helper T (Th) cells, including the dominant subsets such as Th2, Th17, and follicular helper T (Tfh) cells and the inferior subsets such as regulatory T (Treg) cells, shape the immune imbalance of IMN and promote the incidence and development of autoimmune responses. After reviewing the physiological knowledge of various subpopulations of Th cells and combining the existing studies on Th cells in IMN, the role model of Th cells in IMN was explained in this review. Finally, the existing clinical treatment regimens for IMN were reviewed, and the importance of the therapy for Th cells was highlighted.

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Section: Th Cells Involved In the Immune Dysregulation Of Imnmentioning

confidence: 78%

Section: Th Cells Involved In the Immune Dysregulation Of Imnmentioning

confidence: 99%

Helper T Cells in Idiopathic Membranous Nephropathy

et al. 2021

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“…Podocytes are epithelial cells of the glomerular viscera, located outside the glomerular basement membrane, and autoantibodies bind to antigens on the surface of podocytes, forming an in situ immune complex that results in disease ( 2 , 5 ). In situ immune complexes differ from circulating immune complexes in that they do not come into contact with circulating inflammatory mediators and generally do not trigger inflammatory reactions ( 7 ). Therefore, they are more likely to trigger podocyte lesion formation by activating complement, leading to proteinuria and renal tissue damage ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of the Wnt/β‑catenin signaling pathway reduces autophagy levels in complement treated podocytes

et al. 2021

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In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro . Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatment with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy. The results indicated that C5b-9 resulted in a decrease in Akt in podocytes. However, the podocytes preincubated with DKK1 and then attacked by C5b-9 showed an increase in Akt levels. This may explain the observation that blocking the Wnt/β-catenin signaling pathway attenuated C5b-9 podocyte damage, while inhibiting autophagy. The results of the present study also suggest that regulation of these two pathways may serve as a novel method for the treatment of idiopathic membranous nephropathy.

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“…This association between PLA2R autoantibodies and disease activity suggests that the monitoring and quantification of autoantibodies may be for therapy in patients with MN and a valuable tool for determining treatment strategies. In addition to PLA2R, podocyte biomarkers identified in patients with IMN include neural epidermal growth factor-like 1 protein (NELL-1) and thrombospondin type-1 domain-containing 7A (THSD7A), accounting for 5–10% and 3–5% of adult IMN, respectively 15 . Currently, only serum anti-PLA2R antibody detection is widely used in guiding the IMN clinical diagnosis, prognosis, and treatment of IMN.…”

Section: Introductionmentioning

confidence: 99%

Rapid, quantitative, and high-sensitivity detection of anti-phospholipase A2 receptor antibodies using a novel CdSe/ZnS-based fluorescence immunosorbent assay

Qian

Hong

et al. 2021

Sci Rep

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Autoantibodies against M-type phospholipase A2 receptor (PLA2R) serve as specific biomarkers for idiopathic membranous nephropathy (IMN), and its quantification helps monitor disease activity. In this study, we describe a rapid and highly sensitive quantum dots-based immunochromatography assay (QD-ICA) for quantifying PLA2R autoantibodies. Serum samples from 135 biopsy-confirmed patients with nephrotic syndrome were analyzed for PLA2R autoantibodies using the novel QD-ICA as well as commercialized enzyme-linked immunosorbent assay (ELISA). Areas under the receiver operating characteristic curve (AUC-ROC) of QD-ICA were significantly greater than those of ELISA (91.1% [95% CI 85.9–96.3%] and 83.9% [95% CI 76.5–91.2%] respectively; p < 0.01). The detection sensitivity and specificity of QD-ICA (80.9% [95% CI 69.2–89.0%] and 100% [95% CI 93.2–100.0%], respectively) exceeded those of ELISA (72.1% [95% CI 59.7–81.9%] and 98.5% [95% CI 90.9–100.0%], respectively). The optimum cut-off value of QD-ICA was 18.18 relative units (RU)/mL, and the limit of detection was 2.86 RU/mL. The novel QD-ICA outperforms ELISA in detecting PLA2R autoantibodies, with shorter detection time, fewer steps, smaller equipment size, and broader testing application, suggesting its capability to improve IMN diagnosis and monitor patient response to treatment.

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Idiopathic Membranous Nephropathy: Glomerular Pathological Pattern Caused by Extrarenal Immunity Activity

Cited by 30 publications

References 119 publications

Helper T Cells in Idiopathic Membranous Nephropathy

Helper T Cells in Idiopathic Membranous Nephropathy

Inhibition of the Wnt/β‑catenin signaling pathway reduces autophagy levels in complement treated podocytes

Rapid, quantitative, and high-sensitivity detection of anti-phospholipase A2 receptor antibodies using a novel CdSe/ZnS-based fluorescence immunosorbent assay

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