Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis

Chen, Min; Xing, Guangqun; Yu, Feng; Liu, Gang; Zhao, Ming‐Hui

doi:10.1093/ndt/gfn586

Cited by 107 publications

(89 citation statements)

References 20 publications

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“…The same group demonstrated that urinary levels of Bb correlated with the severity of renal injury (14). Moreover, in a cohort of 112 patients with AAV who underwent kidney biopsy, 37 patients showed C3 deposition, and these patients had more severe signs of renal involvement (higher proteinuria and a lower eGFR) (8).…”

Section: Discussionmentioning

confidence: 99%

“…Twenty years later, these findings were reconsidered and prompted subsequent in vivo studies that, through use of murine models of AAV, clearly demonstrated an activation of the terminal part of the complement cascade, particularly of C5, with an engagement of the C5a receptor (4)(5)(6). The relevance of the complement system in the pathogenesis of ANCA-associated necrotizing crescentic GN (NCGN) was further supported by immunohistochemical studies that have confirmed the deposition of C3d, factor B, and factor P in glomeruli and small blood vessels (7,8). A prevailing role of complement alternative pathway (cAP) was postulated when significantly higher plasma levels of sC5b9, that marks the terminal complement pathway, and of C3a and Bb were found in active AAV (9).…”

Section: Introductionmentioning

confidence: 99%

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Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

Manenti

Vaglio

Gnappi

et al. 2015

Clinical Journal of the American Society of Nephrology

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Background and objectives Complement alternative pathway (cAP) activation has recently been recognized as a key pathogenic event in ANCA-associated vasculitis (AAV). cAP dysregulation is also a major determinant of thrombotic microangiopathies (TMA), which can in turn complicate AAV. We explored the prognostic significance of cAP activation and of histologic evidence of TMA in a cohort of patients with renal AAV.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

Manenti

Vaglio

Gnappi

et al. 2015

Clinical Journal of the American Society of Nephrology

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“…Recently, increasing evidences have suggested an important role of complement activation in the pathogenesis of AAV (6)(7)(8)(9)(10)(11)(12)(13). In the animal study by Xiao et al (7), it was found that activation of the alternative complement pathway, but not the classic or lectin pathway, was required for induction of GN with anti-MPO IgG.…”

Section: Introductionmentioning

confidence: 99%

Alternative Complement Pathway Activation Products in Urine and Kidneys of Patients with ANCA-Associated GN

Gou¹,

Yuan²,

Wang³

et al. 2013

Clinical Journal of the American Society of Nephrology

145

100

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SummaryBackground and objectives Previous study revealed that complement activation products of the alternative pathway could be detected in renal specimens of human ANCA-associated vasculitis. The current study aimed to investigate the clinical and pathologic significance of complement activation products in the urine and kidneys of patients with ANCA-associated vasculitis.Design, setting, participants, & measurements Renal biopsy specimens from 29 patients with ANCA-associated vasculitis diagnosed at Peking University First Hospital from January of 2008 to December of 2010 were randomly collected. Urine samples from 27 of 29 patients in active stage and 22 ANCA-associated vasculitis patients in complete remission who were independent of the above-mentioned 29 patients were collected. Urine samples from 28 patients with lupus nephritis and 25 healthy individuals were also collected. The renal deposition of Bb, C3d, and C5b-9 were detected by immunohistochemistry. The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were determined by ELISA.Results The deposition, measured by the mean optical density of Bb, which is an alternative complement pathway marker, in glomeruli correlated with the proportion of total crescents (r=0.50, P=0.006), the extent of interstitial infiltrate (r=0.59, P=0.001), interstitial fibrosis (r=0.45, P=0.01), and tubular atrophy (r=0.55, P=0.002), whereas it correlated inversely with the proportion of normal glomeruli (r=20.49, P=0.008). The urinary levels of Bb, C3a, C5a, and soluble C5b-9 were all significantly higher in active compared with remission stage. The urinary levels of Bb in patients with active ANCA-associated vasculitis correlated with the serum creatinine (r=0.56, P=0.002) and correlated inversely with the proportion of normal glomeruli in renal specimens (r=20.49, P=0.009). ConclusionsThe present study provides additional evidence that complement activation through the alternative pathway occurred in the development of ANCA-associated vasculitis. The renal deposition of Bb and urinary Bb levels were associated with the severity of renal injury.

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“…Most cases (80-90%) are ANCA positive and present morphologically as necrotizing crescentic glomerulonephritis (NCGN). On IF, only scanty Ig and complement (mainly C3c) deposits may be seen in glomeruli [7,129]. According to the Chapel Hill Consensus, ANCA GN includes (SV), such as microscopic polyangiitis (MPA), granulomatosis with polyangiitis (GPA), or eosinophilic granulomatosis with polyangiitis (EGPA) [7,130,131].…”

Section: Pauci-immune Gnmentioning

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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Complement deposition in renal histopathology of patients with ANCA-associated pauci-immune glomerulonephritis

Abstract: Complement deposition was not rare in renal histopathology of human ANCA-associated pauci-immune glomerulonephritis, which was associated with more severe renal injury.

Cited by 107 publications

References 20 publications

Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

Association of Serum C3 Concentration and Histologic Signs of Thrombotic Microangiopathy with Outcomes among Patients with ANCA-Associated Renal Vasculitis

Alternative Complement Pathway Activation Products in Urine and Kidneys of Patients with ANCA-Associated GN

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

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