Eculizumab and Complement Activation in Anti−glomerular Basement Membrane Disease
| Autor: | Frank B. Cortazar, Sujal I. Shah, Astrid Weins, John L. Niles, Reza Zonozi, Pravarut Nithagon, Anushya Jeyabalan, Karen Laliberte |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Basement membrane
Kidney business.industry Eculizumab Anti-Glomerular Basement Membrane Disease medicine.disease Complement system Type IV collagen medicine.anatomical_structure Nephrology Immunology Medicine Rapidly progressive glomerulonephritis Nephrology Rounds business Complement membrane attack complex medicine.drug |
| Zdroj: | Kidney International Reports |
| ISSN: | 2468-0249 |
| DOI: | 10.1016/j.ekir.2021.07.001 |
| Popis: | Anti−glomerular basement membrane (anti-GBM) disease is characterized by pathogenic autoantibodies targeting the α-3 chain of type IV collagen located in the glomerular and alveolar basement membranes. Clinically, it causes rapidly progressive glomerulonephritis and pulmonary hemorrhage. Observational data and mechanistic rationale have largely informed current treatment strategies, including plasmapheresis, glucocorticoids, cyclophosphamide, and rituximab. However, overall and renal prognosis remain guarded, and advancements in therapy are needed. Emerging data have implicated the complement system in the pathogenesis of anti-GBM disease.1, 2, 3, 4, 5 Eculizumab is an anti-C5 monoclonal antibody that blocks the cleavage of C5, which prevents the formation of C5a, the potent leukocyte chemoattractant, and C5b, the initial reagent in the formation of the membrane attack complex (MAC; also known as C5b-9). This provides an immediate inhibition of the downstream proinflammatory and cytotoxic sequelae of the complement system. Here, we report the use of eculizumab as rescue therapy in 2 patients with progressive anti-GBM disease on standard therapies, which, to our knowledge, has not been reported to date. We also present kidney biopsy results with extensive complement staining that add to a limited but growing body of literature on the possible role of complement in the renal damage from anti-GBM disease. |
| Databáze: | OpenAIRE |
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