Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease
Anti-glomerular basement membrane (GBM) disease is a rare but life-threatening autoimmune disorder characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Renal biopsies of anti-GBM patients predominantly show linear deposition of IgG and complement component 3...
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| Format: | Article |
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Frontiers Media S.A.
2023-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229806/full |
| _version_ | 1797682390371401728 |
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| author | Anqi Tang Xin Zhao Tian Tao Dengpiao Xie Bojun Xu Youqun Huang Mingquan Li |
| author_facet | Anqi Tang Xin Zhao Tian Tao Dengpiao Xie Bojun Xu Youqun Huang Mingquan Li |
| author_sort | Anqi Tang |
| collection | DOAJ |
| description | Anti-glomerular basement membrane (GBM) disease is a rare but life-threatening autoimmune disorder characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Renal biopsies of anti-GBM patients predominantly show linear deposition of IgG and complement component 3 (C3), indicating a close association between antigen-antibody reactions and subsequent complement activation in the pathogenesis of the disease. All three major pathways of complement activation, including the classical, lectin, and alternative pathways, are involved in human anti-GBM disease. Several complement factors, such as C3, C5b-9, and factor B, show a positive correlation with the severity of the renal injury and act as risk factors for renal outcomes. Furthermore, compared to patients with single positivity for anti-GBM antibodies, individuals who are double-seropositive for anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM antibodies exhibit a unique clinical phenotype that lies between ANCA-associated vasculitis (AAV) and anti-GBM disease. Complement activation may serve as a potential “bridge” for triggering both AAV and anti-GBM conditions. The aim of this article is to provide a comprehensive review of the latest clinical evidence regarding the role of complement activation in anti-GBM disease. Furthermore, potential therapeutic strategies targeting complement components and associated precautions are discussed, to establish a theoretical basis for complement-targeted therapies. |
| first_indexed | 2024-03-12T00:00:00Z |
| format | Article |
| id | doaj.art-4a49fad99acf4b70a804e3229655b735 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-12T00:00:00Z |
| publishDate | 2023-09-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-4a49fad99acf4b70a804e3229655b7352023-09-18T05:04:48ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-09-011410.3389/fimmu.2023.12298061229806Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane diseaseAnqi Tang0Xin Zhao1Tian Tao2Dengpiao Xie3Bojun Xu4Youqun Huang5Mingquan Li6Clinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaClinical Medical College, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaDepartment of Nephrology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaAnti-glomerular basement membrane (GBM) disease is a rare but life-threatening autoimmune disorder characterized by rapidly progressive glomerulonephritis with or without pulmonary hemorrhage. Renal biopsies of anti-GBM patients predominantly show linear deposition of IgG and complement component 3 (C3), indicating a close association between antigen-antibody reactions and subsequent complement activation in the pathogenesis of the disease. All three major pathways of complement activation, including the classical, lectin, and alternative pathways, are involved in human anti-GBM disease. Several complement factors, such as C3, C5b-9, and factor B, show a positive correlation with the severity of the renal injury and act as risk factors for renal outcomes. Furthermore, compared to patients with single positivity for anti-GBM antibodies, individuals who are double-seropositive for anti-neutrophil cytoplasmic antibody (ANCA) and anti-GBM antibodies exhibit a unique clinical phenotype that lies between ANCA-associated vasculitis (AAV) and anti-GBM disease. Complement activation may serve as a potential “bridge” for triggering both AAV and anti-GBM conditions. The aim of this article is to provide a comprehensive review of the latest clinical evidence regarding the role of complement activation in anti-GBM disease. Furthermore, potential therapeutic strategies targeting complement components and associated precautions are discussed, to establish a theoretical basis for complement-targeted therapies.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229806/fullanti-glomerular basement membrane diseasecomplementautoimmune nephropathycomplement activationcomplement therapeuticsemerging therapies |
| spellingShingle | Anqi Tang Xin Zhao Tian Tao Dengpiao Xie Bojun Xu Youqun Huang Mingquan Li Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease Frontiers in Immunology anti-glomerular basement membrane disease complement autoimmune nephropathy complement activation complement therapeutics emerging therapies |
| title | Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease |
| title_full | Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease |
| title_fullStr | Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease |
| title_full_unstemmed | Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease |
| title_short | Unleashing the power of complement activation: unraveling renal damage in human anti-glomerular basement membrane disease |
| title_sort | unleashing the power of complement activation unraveling renal damage in human anti glomerular basement membrane disease |
| topic | anti-glomerular basement membrane disease complement autoimmune nephropathy complement activation complement therapeutics emerging therapies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1229806/full |
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