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- W4318344487 abstract "Abstract Membranous nephropathy (MN) is an antibody-mediated autoimmune disease characterized by glomerular immune complexes containing complement components. However, both the initiation pathways and the pathogenic significance of complement activation in MN are poorly understood. Here, we show that components from all three complement pathways (alternative, classical and lectin) are found in renal biopsies from patients with MN. Proximity ligation assays to directly visualize complement assembly in the tissue reveal dominant activation via the classical pathway, with a close correlation to the degree of glomerular C1q-binding IgG subclasses. In an antigen-specific autoimmune mouse model of MN, glomerular damage and proteinuria are reduced in complement-deficient mice compared with wild-type littermates. Severe disease with progressive ascites, accompanied by extensive loss of the integral podocyte slit diaphragm proteins, nephrin and neph1, only occur in wild-type animals. Finally, targeted silencing of C3 using RNA interference after the onset of proteinuria significantly attenuates disease. Our study shows that, in MN, complement is primarily activated via the classical pathway and targeting complement components such as C3 may represent a promising therapeutic strategy." @default.
- W4318344487 created "2023-01-28" @default.
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- W4318344487 date "2023-01-28" @default.
- W4318344487 modified "2023-10-18" @default.
- W4318344487 title "The classical pathway triggers pathogenic complement activation in membranous nephropathy" @default.
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- W4318344487 cites W2004844864 @default.
- W4318344487 cites W2008486735 @default.
- W4318344487 cites W2037897625 @default.
- W4318344487 cites W2055761277 @default.
- W4318344487 cites W2064922682 @default.
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- W4318344487 cites W2140297546 @default.
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- W4318344487 cites W2169656611 @default.
- W4318344487 cites W2182390629 @default.
- W4318344487 cites W2211752697 @default.
- W4318344487 cites W2345937290 @default.
- W4318344487 cites W2395598045 @default.
- W4318344487 cites W2439974361 @default.
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- W4318344487 cites W2538483139 @default.
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- W4318344487 cites W2745663953 @default.
- W4318344487 cites W2755483399 @default.
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- W4318344487 cites W2792441704 @default.
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- W4318344487 cites W2894235599 @default.
- W4318344487 cites W2905773539 @default.
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- W4318344487 cites W2938956881 @default.
- W4318344487 cites W2944262545 @default.
- W4318344487 cites W2963020634 @default.
- W4318344487 cites W2970501086 @default.
- W4318344487 cites W2977665112 @default.
- W4318344487 cites W2989082294 @default.
- W4318344487 cites W2995516475 @default.
- W4318344487 cites W2996827211 @default.
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- W4318344487 cites W3019741502 @default.
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- W4318344487 cites W3084391638 @default.
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- W4318344487 cites W3151337960 @default.
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- W4318344487 cites W3164369719 @default.
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- W4318344487 doi "https://doi.org/10.1038/s41467-023-36068-0" @default.
- W4318344487 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36709213" @default.
- W4318344487 hasPublicationYear "2023" @default.
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