A novel CFHR1-CFHR5 hybrid leads to a familial dominant C3 glomerulopathy

Togarsimalemath, Shambhuprasad Kotresh; Sethi, Sidharth Kumar; Duggal, Rajan; Quintrec, Moglie Le; Jha, Pranaw Kumar; Daniel, Régis; Gonnet, Florence; Bansal, Shyam Bihari; Roumenina, Lubka T.; Frémeaux‐Bacchi, Véronique; Kher, Vijay; Dragon-Durey, Marie-Agnès

doi:10.1016/j.kint.2017.04.025

Cited by 36 publications

(36 citation statements)

References 29 publications

(44 reference statements)

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“…Previous studies had focused on the role of innate immune system in the tumorigenesis and progression of hepatocellular carcinoma and other malignancies . One of the critical complement regulators is complement factor H (CFH), which performs as part of a protein family that includes CFHL3 and five CFHR proteins . Plenty of researchers claimed that immune‐related tumor development could be affected by the complement system, including how CFH, complement proteins C7, and complement factor H appear to be connected with ovarian cancer, and liver cancer .…”

Section: Discussionmentioning

confidence: 99%

“…The complement system is a key component of innate immunity and can promote or inhibit tumorigenesis . The complement factor H family comprises factor H (FH), complement factor H‐like protein (CFHL1), and complement factor H‐related protein 1‐5 (CFHR1‐CFHR5) . CFHR3, also known as DOWN16 and FHR‐3, is a negative complement activation regulator, which performs as an essential member of the innate immune system.…”

Section: Introductionmentioning

confidence: 99%

“…9,10 The complement factor H family comprises factor H (FH), complement factor H-like protein (CFHL1), and complement factor H-related protein 1-5 (CFHR1-CFHR5). 11 CFHR3, also known as DOWN16 and FHR-3, is a negative complement activation regulator, which performs as an essential member of the innate immune system. Previous studies have demonstrated a connection between the CFHR3 and immune system diseases, such as atypical hemolytic-uremic syndrome, 12 macular degeneration, 13 IgA nephropathy, 14 and systemic lupus erythematosus.…”

Section: Introductionmentioning

confidence: 99%

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CFHR3 is a potential novel biomarker for hepatocellular carcinoma

Liu

Zhao

2019

J of Cellular Biochemistry

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Complement factor H‐related 3 (CFHR3) is a protein‐coding gene acting in various diseases. However, its prognostic values of CFHR3 in hepatocellular carcinoma (HCC) are not understandable. Therefore, we present a further study on CFHR3 in HCC. CFHR3 expression data were acquired from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). We compared the differential expression of CFHR3 between the low‐stage (stage I and II) and high‐stage (stage III and IV) patients with HCC in the TCGA and ICGC cohorts. Furthermore, we assessed the CFHR3 expression as a prognostic marker using the Kaplan‐Meier survival analysis, univariate, and multivariate analysis. The Kaplan‐Meier analysis declared that CFHR3 overexpression was correlated with a good prognosis for HCC patients. Multivariate analysis proved the prognostic significance of CFHR3 expression levels (P < .001 and .003 for TCGA and ICGC, respectively). Immune‐related scores in low‐risk cohorts were higher than high‐risk cohorts. Gene set enrichment analysis implied that the low CFHR3 expression phenotype was significantly enriched in critical biological functions and pathways and was associated with tumorigenesis, such as regulation of cell activation cycle, and the WNT and NOTCH signal pathway. Above all, CFHR3 could be a novel prognostic biomarker and therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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CFHR3 is a potential novel biomarker for hepatocellular carcinoma

Liu

Zhao

2019

J of Cellular Biochemistry

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“…Single SLE cases associated with different C3 mutations have been reported in the Japanese population [73,74]. Further, first described in patients of Cypriot origin, familial cases of C3G, associated with mutant CFHR proteins, have also been found in patients of other ethnicities [39,40,[75][76][77][78].…”

Section: The Genetic Background Of the Ap Abnormalities In Glomerularmentioning

confidence: 97%

“…Also, in two patients, complete CFHR1 deficiency due to CFHR3-1Δ was observed. Unlike the above-mentioned hybrid proteins, mutant CFHR1-5 was created as a result of a genetic rearrangement of 3 CFHRs genes, namely the heterozygous 147-kilobase deletion, spanning from CFHR1 intron 4 to the 5′ region of CFHR5 [78]. Altogether, the exact pathogenic mechanism by which the genetic abnormalities in CFHRs cause the disease is still unknown, but likely involves deregulation of the CS.…”

Section: Hereditary Ap Abnormalities In C3gmentioning

confidence: 99%

The role of the alternative pathway of complement activation in glomerular diseases

2018

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The complement system (CS) has recently been recognized as a bridge between innate and adaptive immunity that constitutes a very complex mechanism controlling the clearance of pathogens, cellular debris, and immune complexes. Out of three known pathways of complement activation, the alternative pathway (AP) plays a critical role in host defense by amplifying the complement response, independently of initiation pathway and continuously maintaining low-level activity in a process called 'thick-over.' A key molecule of the CS is C3, in which the AP is constantly activated. To prevent host cell destruction, a group of the AP regulators tightly controls this pathway of the CS activation. Acquired and genetic abnormalities of the CS may alter the delicate balance between enhancing and inhibiting the AP cascade. These can lead to the uncontrolled CS activation, inflammatory response, and subsequent tissue damage. Since complement components are locally produced and activated in the kidney, the abnormalities targeting the AP may cause glomerular injury. C3 glomerulopathy is a new entity, in which the AP dysregulation has been well established. However, recent studies indicate that the AP may also contribute to a wide range of kidney pathologies, including immune-complex-mediated glomerulonephritis (GN), pauci-immune GN, and primary membranous nephropathy (PMN). This article provides insight into current knowledge on the role of the AP in the pathogenesis of glomerular diseases, focusing mainly on various types of primary and secondary GN and PMN.

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