Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation

Miura, Takayoshi; Goto, Shin; Iguchi, Seitaro; Shimada, Hideaki; Ueno, Mitsuhiro; Nishi, Shinichi; Narita, Ichiei

doi:10.1007/s10157-010-0358-0

Cited by 4 publications

(1 citation statement)

References 22 publications

(35 reference statements)

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“…An epidemiological study provided strong evidence for a relationship between C9 deficiency and meningococcal sepsis and meningitis (25). An Arg95 stop mutation of exon 4 in the complement C9 gene is common in individuals in Japan with C9 deficiency, and the lack of the membrane attack complex due to this mutation predisposed patients to pathognomonic glomerulonephritis (26). Morgan et al studied the concentration of the terminal component of complement (C9) in cerebrospinal fluid (CSF) and plasma from 35 patients with multiple sclerosis and 55 controls with other neurological diseases.…”

Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function

Kim

Meyer

Bisceglie

et al. 2013

J Virol

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Hepatitis C virus (HCV) proteins inhibit complement component expression, which may attenuate immunity against infection. In this study, we examined whether HCV regulates the membrane attack complex (MAC) via complement component C9. MAC is composed of C5b to C9 (C5b-9) and mediates cell lysis of invaded pathogens. Liver biopsy specimens from chronically HCVinfected patients exhibited a lower level of C9 mRNA expression than liver biopsy specimens from unrelated disease or healthy control human liver RNA. Hepatocytes infected with cell culture-grown HCV or expressing HCV core protein also displayed significant repression of C9 mRNA and protein levels. Promoter analysis suggested that the T cell factor-4 (TCF-4E) transcription factor is responsible for HCV core-mediated C9 promoter regulation. Sera from chronically HCV-infected patients displayed a lower level of C5b-9 and a reduced antimicrobial effect on model organisms compared to unrelated patient sera or sera from healthy volunteers. Together, these results for C9 regulation by HCV core protein coupled with functional impairment of the membrane attack complex underscore HCV-mediated attenuation of immune mechanisms.

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Section: Discussionmentioning

confidence: 99%

Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function

Kim

Meyer

Bisceglie

et al. 2013

J Virol

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Role of complement in glomerular diseases

Mao

Zhang

2015

Journal of Receptors and Signal Transduction

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The complement system, composed of nearly 30 proteins, is a key regulator of immunity. The complement system is critical for protecting hosts from invading pathogens. Dysregulation of this system is associated with susceptibility to infection and various autoimmune diseases. Furthermore, complement activation due to the defective regulation of the alternative pathway will induce glomerular diseases. Anti-complement therapy has been applied in various glomerular diseases. Signaling pathways might be very important in the pathogenesis of glomerular diseases. This review will give a relatively complete signaling pathway flowchart for complement and a comprehensive understanding of the underlying role of complement in glomerular diseases.

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Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

et al. 2021

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The membrane attack complex—also known as C5b-9—is the end-product of the classical, lectin, and alternative complement pathways. It is thought to play an important role in the pathogenesis of various kidney diseases by causing cellular injury and tissue inflammation, resulting in sclerosis and fibrosis. These deleterious effects are, consequently, targeted in the development of novel therapies that inhibit the formation of C5b-9, such as eculizumab. To clarify how C5b-9 contributes to kidney disease and to predict which patients benefit from such therapy, knowledge on deposition of C5b-9 in the kidney is essential. Because immunohistochemical staining of C5b-9 has not been routinely conducted and never been compared across studies, we provide a review of studies on deposition of C5b-9 in healthy and diseased human kidneys. We describe techniques to stain deposits and compare the occurrence of deposits in healthy kidneys and in a wide spectrum of kidney diseases, including hypertensive nephropathy, diabetic nephropathy, membranous nephropathy, IgA nephropathy, lupus nephritis, C3 glomerulopathy, and thrombotic microangiopathies such as the atypical hemolytic uremic syndrome, vasculitis, interstitial nephritis, acute tubular necrosis, kidney tumors, and rejection of kidney transplants. We summarize how these deposits are related with other histological lesions and clinical characteristics. We evaluate the prognostic relevance of these deposits in the light of possible treatment with complement inhibitors.

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Membranoproliferative pattern of glomerular injury associated with complement component 9 deficiency due to Arg95Stop mutation

Abstract: These results suggested that the lack of membrane attack complex because of an Arg95Stop mutation of the C9 gene predisposed patients to pathognomonic glomerulonephritis.

Cited by 4 publications

References 22 publications

Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function

Hepatitis C Virus Suppresses C9 Complement Synthesis and Impairs Membrane Attack Complex Function

Role of complement in glomerular diseases

Deposition of the Membrane Attack Complex in Healthy and Diseased Human Kidneys

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