Current Understanding of the Role of Complement in IgA Nephropathy

Maillard, Nicolas; Wyatt, Robert; Julian, Bruce A.; Kiryluk, Krzysztof; Gharavi, Ali G.; Frémeaux‐Bacchi, Véronique; Novák, Jan

doi:10.1681/asn.2014101000

Cited by 274 publications

(249 citation statements)

References 98 publications

(89 reference statements)

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“…The red arrows indicate the site of the common C3 polymorphisms (F/S and HAV 4-1+/−), located in MG1 and MG3, respectively. The diagram was based on Maillard et al [32], modified important mechanism preventing the destruction of the host cells [3,[13][14][15].…”

Section: C3 Structurementioning

confidence: 99%

“…3). Its serum concentrations may range from 110 to 615 μg/mL [1,4,31,32]. The molecular structure of CFH consists of 20 SCRs, which are arranged Fig.…”

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

“…In fact, it is the only AP inhibitor present on the GBM in glomeruli. Complement FH-like protein (CFHL1), a splice form of CFH, consisting of 7N-terminal domains of CFH has also been reported [1,20,[24][25][26]32]. Recently described, the complement FH-related proteins (CFHR1-5) are also the members of the RCA gene cluster, encoded by five genes on chromosome 1q32.…”

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

“…While CFHR3 and CFHR4 were revealed to possess a weak FI cofactor activity, CFHR5 bound C3b in vitro and exhibited both FI cofactor and decay acceleration activity. However, most of these AP-regulating activities of CFHRs are weak, and they were observed in in vitro assays, which used non-physiological CFHRs concentrations [23,24,31,32,[34][35][36].…”

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

“…The activation of immune complexes by the CP led to the assumption that other complement pathways are not involved in the disease pathogenesis. However, glomerular co-deposition of CFHR5, CFH, and FP has been found in MPGN I, LN and IgAN cases, indicating the AP involvement in these diseases [7,8,32,110,111]. In MPGN I patients, Servais et al reported low AP proteins levels, such as C3, CFB, CFH, and CFI (in 46.3, 34.1, 4.9, and 7.3% of cases, respectively) and the prevalence of the C3NeF (in 53.6% cases), what suggested the AP activation [62].…”

Section: Immune-complex Glomerulonephritismentioning

confidence: 99%

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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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Section: C3 Structurementioning

confidence: 99%

“…3). Its serum concentrations may range from 110 to 615 μg/mL [1,4,31,32]. The molecular structure of CFH consists of 20 SCRs, which are arranged Fig.…”

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

Section: The Alternative Pathway Regulating Proteinsmentioning

confidence: 99%

Section: Immune-complex Glomerulonephritismentioning

confidence: 99%

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

2018

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Oral Glucocorticoids for IgA Nephropathy

Campbell

2022

JAMA

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Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy

Wong

Hladunewich

et al. 2022

JAMA

163

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The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. OBJECTIVE To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline.DESIGN, SETTING, AND PARTICIPANTS An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m 2 after at least 3 months of optimized background care from 67 centers in

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Current Understanding of the Role of Complement in IgA Nephropathy

Cited by 274 publications

References 98 publications

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

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

Oral Glucocorticoids for IgA Nephropathy

Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy

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