Complement Signaling and Regulated Cell Death in Immune-Mediated Glomerular Injury.
- 1Department of Nephrology, School of Medicine, University of Crete, 71003 Heraklion, Greece.
- 2Department of Nephrology, Heraklion University Hospital, 71500 Crete, Greece.
Abstract
The complement system is a central component of innate immunity, with essential roles in host defense, immune complex clearance, apoptotic cell removal, and tissue homeostasis. In the kidney, glomerular and tubular structures are continuously exposed to circulating and locally produced complement components. Dysregulated complement activation contributes to a wide spectrum of renal diseases, including membranous nephropathy, IgA nephropathy, ANCA-associated glomerulonephritis, lupus nephritis, thrombotic Imicroangiopathies and selected forms of podocyte injury. Regulated cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, further shape renal inflammation and injury. These pathways interact bidirectionally with complement: complement effectors such as C3a, C5a, and the membrane attack complex can trigger or modulate inflammatory cell death, whereas dying cells release danger signals and altered-self structures that amplify complement activation. This crosstalk creates self-reinforcing loops of necroinflammation, glomerular injury, tubular damage, and fibrosis. This comprehensive review integrates current evidence on complement biology and regulated cell death in renal disease, emphasizing mechanistic links, disease-specific pathways, diagnostic implications, and emerging therapeutic opportunities. Understanding this interaction may support more precise approaches to complement inhibition, modulation of cell death, and personalized treatment in immune-mediated kidney disease.
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BibTeX
@article{tzali2026complement,
title = {{Complement Signaling and Regulated Cell Death in Immune-Mediated Glomerular Injury.}},
author = {Eleni Tzali and Christos Pleros and Kostas Stylianou and Ioannis Petrakis},
journal = {Medicina (Kaunas, Lithuania)},
year = {2026},
month = oct,
doi = {10.3390/medicina62101924},
url = {https://europepmc.org/article/MED/42942455},
note = {CC BY},
}
RIS
TY - JOUR
TI - Complement Signaling and Regulated Cell Death in Immune-Mediated Glomerular Injury.
AU - Eleni Tzali
AU - Christos Pleros
AU - Kostas Stylianou
AU - Ioannis Petrakis
PY - 2026
DA - 2026/10/06
JO - Medicina (Kaunas, Lithuania)
DO - 10.3390/medicina62101924
UR - https://europepmc.org/article/MED/42942455
AB - The complement system is a central component of innate immunity, with essential roles in host defense, immune complex clearance, apoptotic cell removal, and tissue homeostasis. In the kidney, glomerular and tubular structures are continuously exposed to circulating and locally produced complement components. Dysregulated complement activation contributes to a wide spectrum of renal diseases, including membranous nephropathy, IgA nephropathy, ANCA-associated glomerulonephritis, lupus nephritis, thrombotic Imicroangiopathies and selected forms of podocyte injury. Regulated cell death pathways, including apoptosis, necroptosis, pyroptosis, ferroptosis, and autophagy, further shape renal inflammation and injury. These pathways interact bidirectionally with complement: complement effectors such as C3a, C5a, and the membrane attack complex can trigger or modulate inflammatory cell death, whereas dying cells release danger signals and altered-self structures that amplify complement activation. This crosstalk creates self-reinforcing loops of necroinflammation, glomerular injury, tubular damage, and fibrosis. This comprehensive review integrates current evidence on complement biology and regulated cell death in renal disease, emphasizing mechanistic links, disease-specific pathways, diagnostic implications, and emerging therapeutic opportunities. Understanding this interaction may support more precise approaches to complement inhibition, modulation of cell death, and personalized treatment in immune-mediated kidney disease.
SN - 1010-660X
SN - 1648-9144
ER -