What a pathologist needs to know about disorders of the complement system
Authors:
Eva Honsová
Authors‘ workplace:
Unilabs Patologie, Praha
Published in:
Čes.-slov. Patol., 60, 2024, No. 3, p. 144-149
Category:
Reviews Article
Overview
The complement system is an important component of innate immunity, which is part of the first line of defense against infections. In addition, complement plays an important role in the removal of apoptotic and damaged endogenous cells and, according to recent discoveries, contributes significantly to the homeostasis of the organism. The complement system includes several dozen soluble and membrane-bound proteins, which, after activation, function as a cascade, at the end of which is the elimination of the infectious agent. Complement activation occurs through one of 3 pathways (classical, lectin, and alternative) and all 3 pathways lead to the central C3 component. The cleavage of C3 starts the activation of the so-called effector terminal cascade, which participates in the elimination of pathogens through pro-inflammatory mechanisms, opsonization and, at the end, the creation of a channel in the basement membrane. The systematic control of complement activation plays an important role, because that represents prevention against damage to one’s own tissues. Especially, the alternative pathway, which provides more than 80% of the activity of the terminal complement cascade, requires tight control. Dysregulation of complement and especially its alternative pathways is behind many acute and chronic diseases.
Keywords:
thrombotic microangiopathy – Complement – alternative pathway – aHUS – C3 nephropathy
Sources
- Kolev M, Le Friec G, Kemper C. Complement – tapping into new sites and effector systems. Nat Rev Immunol 2014; (14): 811–820.
- Harboe M, Mollnes TE. The alternative complement pathway revisited. J Cell Mol Med 2008; 12(4): 1074–1084.
- Merle N, Noe R, Halbwachs-Mecarelli L, et al. Complement system part II: role in immunity. Frontiers in Immunology 2015;
- de Nooijer AH, Grondman I, Janssen N, et al. Complement activation in the disease course of coronavirus disease 2019 and its effect on clinical outcomes. J Infect Dis 2021; (223): 214-224.
- Perico L, Morigi M, Pezzota A, et al. SARS-CoV-2 spike protein induces lung endothelial cell dysfunction and thrombo-inflammation depending on the C3a/C3a receptor signalling. Sci Rep 2023
- Warwicker P, Donne RL, Goodship JA, et al. Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency. Nephrol Dial Transplant 1999; 14(5): 1229-1233.
- Noris M, and Remuzzi G. Glomerular diseases dependent on complement activation, including atypical hemolytic uremic syndrome, membranoproliferative glomerulonephritis, and C3 glomerulopthy: Core curriculum 2015. Am J Kidney Dis 2015; (66): 359-499.
- Noris M, Galbusera M, Gastoldi S, et al. Dynamics of complement activation in aHUS and how to monitor eculizumab therapy. Blood 2014; 124(11): 1715-1726.
- Noris M and Remuzzi G. Eculizumab-Every Fifteen Days Forever? Kidney Int Rep 2023; (8): 4-7.
- Noris M, Donadelli R and Remuzzi G. Autoimmune abnormalities of the alternative complement pathway in membranoproliferative glomerulonephritis and C3 glomerulopathy. Pediatric Nephrol 2019; (34): 1311-1323.
- Tarragon Estebanez B, Bomback AS. C3 Glomerulopathy: Novel Treatment Paradigms. Kidney Int Rep 2023;
- Sethi S, Fervenza FC, Zhang Y, et al. Atypical post-infectious glomerulonephritis is associated with abnormalities in the alternative pathway of complement. Kidney Int 2013; (83): 293-299..
- Khalighi MA, Wang S, Henriksen K, et al. Revisiting post-infectious glomerulonephritis in the emerging era of C3 glomerulopathy. Clin Kidney J 2016; (9): 397-402.
- Avasare R, Andeen N, Havasi A, et al. The Clone Wars: Diagnosing and Treating Dysproteinemic Kidney Disease in the Modern Era. J Clin Med 2021; 10(8): 1633.
- Macedo ACL and Isaac L. Systemic Lupus Erythematosus and Deficiencies of Early Components of the Complement Classical Pathway. Front Immunol 2016;
- Salant DJ, Belok S, Madaio MP, et al. A new role for complement in experimental membranous nephropathy in rats. J Clin Invest 1980; (66): 1339-1350.
- Zipfel PF, Wiech T, Grone HJ, et al. Complement catalyzing glomerular diseases. Cell and Tissue Research 2012; (385): 355-370.
- Thurnberg D, Lewis M, Moss J, et al. Complement activation contributes to both glomerular and tubulointerstitial damage in adriamycin nephropathy in mice. J Immunol 2006; (177): 4094-4102.
- Boudhabhay I, Poillerat V, Grunenwald A, et al. Complement activation is crucial driver of acute kidney injury in rhabdomyolysis. Kidney Int 2021; (99): 581-597.
Labels
Anatomical pathology Forensic medical examiner ToxicologyArticle was published in
Czecho-Slovak Pathology
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