Differential Deposition of C4d and MBL in Glomeruli of Patients with ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis

Xing, Guangqun; Chen, Min; Liu, Gang; Zheng, Xin; E, Jie; Zhao, Ming‐Hui

doi:10.1007/s10875-009-9344-2

Cited by 45 publications

(48 citation statements)

References 34 publications

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“…Data about C4d renal deposition in AAV are scarce. A previous small study on seven ANCA-positive patients (7) documented C4d negativity in NCGN, but later C4d was found to coexist with C3d in renal biopsy specimens from patients with ANCA-negative pauci-immune NCGN (16). In this study, the activation of the complement lectin pathway was hypothesized as superimposed on the activation of the cAP via the production of C3b.…”

Section: Discussionmentioning

confidence: 68%

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: 68%

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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“…The involvement of MBL in glomeruli was reflected by a poor renal prognosis, e.g. more severe renal disease in cases of IgA nephropathy (Roos et al [19]) and in patients with antinuclear antibody-negative Pauci-immune crescentic glomerulonephritis (Xing et al [20]). In dialysis patients (Ibernon et al [21]), low pretransplant levels of MBL were associated with chronic inflammation, new-onset diabetes mellitus after transplantation, and infection.…”

Section: Introductionmentioning

confidence: 99%

Functional Mannose-Binding Lectin Levels in Patients with End-Stage Renal Disease on Maintenance Hemodialysis

Satomura¹,

Fujita

Yanai

et al. 2012

J Innate Immun

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Background: Innate immunity is generally impaired in chronic renal failure (CRF). Mannose-binding lectin (MBL) has an important role in first-line host defense against pathogens via the lectin pathway. We recently reported that functional MBL was significantly lower in CRF patients than in healthy subjects. In this study, we aimed to determine whether functional MBL would be improved following hemodialysis (HD) therapy. Methods: This study included 22 patients with end-stage renal disease (ESRD) on maintenance HD. Functional MBL was measured every 6 months for 1 year after HD using an enzyme-linked immunosorbent assay. Results: Median serum functional MBL levels of ESRD patients were significantly higher after 6 and 12 months than at the start of HD therapy (p < 0.05 and p < 0.01, respectively). Furthermore, median functional MBL levels at 12 months were significantly higher than those at 6 months (p < 0.05). Conclusions: We found significant increases in serum functional MBL levels in patients on HD. Our results indicated that HD tailored to remove uremic toxins could improve functional MBL levels in these patients.

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“…C4d is widely used as marker of antibody-mediated rejection, 14,15 and studies have also shown that it is positive in immune complex-or Ig-mediated GN, such as lupus nephritis, membranous nephropathy, antiglomerular basement membrane GN, and antineutrophil cytoplasmic antibody crescentic GN. [16][17][18][19][20][21][22] Recently, it was shown that C4d staining in IgA nephropathy might serve as a poor prognostic factor. 11 However, studies have not been done regarding its potential role in the diagnosis of C3 glomerulopathy.…”

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confidence: 99%

C4d as a Diagnostic Tool in Proliferative GN

Sethi¹,

Nasr²,

Vriese

et al. 2015

Journal of the American Society of Nephrology

110

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Proliferative GN is classified as immune complex-mediated or complement-mediated (C3 glomerulopathy). Immune complex-mediated GN results from glomerular deposition of immune-complexes/Ig and C3; the C3 is derived from activation of the classical and/or lectin pathways of complement. C3 glomerulopathy results from deposition of C3 and other complement fragments with minimal or no deposition of immune complexes/ Ig; the C3 is derived from activation of the alternative pathway of complement. C4d is a byproduct of activation of the classic and lectin pathways. Although widely used as a marker for antibody-mediated rejection, the significance of C4d in C3 glomerulopathy is undetermined. We studied glomerular C4d staining in 18 biopsy specimens of immune-complex GN, 30 biopsy specimens of C3 GN, and 13 biopsy specimens of postinfectious GN. All specimens of immune complex-mediated GN, except two specimens of IgA nephropathy and one specimen of sclerosing membranoproliferative GN, showed bright (2-3+) C4d staining. The staining pattern of C4d mirrored the staining patterns of Ig and C3. Conversely, C4d staining was completely negative in 24 (80%) of 30 specimens of C3 glomerulopathy, and only trace/1+ C4d staining was detected in six (20%) specimens. With regard to postinfectious GN, C4d staining was negative in six (46%) of 13 specimens, suggesting an abnormality in the alternative pathway, and it was positive in seven (54%) specimens. To summarize, C4d serves as a positive marker for immune complex-mediated GN but is absent or minimally detected in C3 glomerulopathy. On the other hand, complement-mediated GN, also termed C3 glomerulopathy, is caused by glomerular deposition of complement factors resulting from dysregulation of the alternative pathway (AP) of complement. 4-7 C3 glomerulopathy includes C3 GN and dense deposit disease (DDD). 8 Immunofluorescence is the key to the Mayo classification. Immune complex-mediated GN shows Ig on immunofluorescence, often along with C3, the latter because of activation of the CP by the immune complexes or LP by microbial surfaces. On the other hand, there is bright staining for C3, and Igs are typically negative in complement-mediated GN/C3 glomerulopathy. However, a proportion of C3 glomerulopathy biopsies may show small amounts of Igs on immunofluorescence. 9,10 As a result, the definition of C3 glomerulopathy now states that C3 staining should be dominant and at least 2 orders of

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Differential Deposition of C4d and MBL in Glomeruli of Patients with ANCA-Negative Pauci-Immune Crescentic Glomerulonephritis

Abstract: Complement activation was involved in renal damage of human ANCA-negative pauci-immune CrGN but with heterogeneous activation pathways. Positive staining of C4d and MBL might be associated with poor renal outcome.

Cited by 45 publications

References 34 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

Functional Mannose-Binding Lectin Levels in Patients with End-Stage Renal Disease on Maintenance Hemodialysis

C4d as a Diagnostic Tool in Proliferative GN

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