Demonstration of C3d Deposits in Membranous Nephropathy

Doi, Toshio; Kanatsu, Kazuro; Nagai, Hirokazu; Suehiro, Fumihiko; Kubo, Takashi; Hamashima, Yoshihiro

doi:10.1159/000183255

Cited by 54 publications

(54 citation statements)

References 7 publications

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“…It has been suggested that idiopathic MGN in adults is characterized by deposition of the predominantly IgG4 subclass (11)(12)(13)(14). The characteristics of IgG4 may explain a generally observed finding in adult idiopathic MGN of abundant C3 with little C1q deposition, which reflects activation of the alternative, rather than classical, complement pathway (11).…”

Section: Discussionmentioning

confidence: 99%

Segmental Membranous Glomerulonephritis in Children

Obana¹,

Nakanishi²,

Sako³

et al. 2006

Clinical Journal of the American Society of Nephrology

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Generally, idiopathic membranous glomerulonephritis (MGN) is a global glomerular disease that affects the whole of the glomerulus. However, idiopathic segmental MGN (SMGN) that shows IgG deposits in a portion of the glomerulus is encountered often. For clarification of whether SMGN is the same entity as idiopathic global MGN (GMGN), the two diseases were compared. From 1978 to 2004, 38 children (11 with SMGN and 27 with GMGN) received a diagnosis of idiopathic MGN. Immunofluorescence microscopy showed segmental granular IgG staining along the capillary loops in SMGN, whereas GMGN showed global staining. On light microscopy, SMGN showed segmental thickening of the glomerular basement membrane, with spike formation, whereas GMGN showed global lesions. The frequency of C1q deposits in SMGN was significantly higher than that in GMGN (91 versus 41%; P < 0.01). On electron microscopy, mesangial electron-dense deposits were detected in 10 (91%) cases of SMGN and also were found in the subepithelial and intramembranous area, whereas only six (22%) cases of GMGN had mesangial electron-dense deposits (P < 0.001). There were no significant differences in clinical features between the groups. Two children with SMGN underwent a repeat biopsy 3 yr after the first biopsy, and both patients again showed SMGN. At the final observation (mean observation time 7.5 yr in SMGN and 12.4 yr in GMGN), all children of both groups had a good outcome. In conclusion, these findings as a whole suggest that SMGN may be another glomerular disease entity with child predominance that is distinctive from GMGN.

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Section: Discussionmentioning

confidence: 99%

Segmental Membranous Glomerulonephritis in Children

Obana¹,

Nakanishi²,

Sako³

et al. 2006

Clinical Journal of the American Society of Nephrology

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“…Activation of the com plement system can occur by classical or alternative path ways and lead to generation of several biologically active fragments. The complement system plays a central role in the mediation of immunological tissue injuries [4] such as various glomerular diseases [12][13][14], However, in these reports, most diseases in cases of isolated C3 deposition showed a benign course and these patients did not mani fest immunologically active reactions such as mononuc lear cell infiltration, increase of polymorphs in the glom eruli, cellular crescents, global sclerosis or necrosis. Therefore, the groups with isolated C3 deposition re ported by these authors may include the cases with iso lated C3d deposition observed in our study.…”

Section: Discussionmentioning

confidence: 99%

Clinicopathological Study of Patients with Mesangial Isolated C3d Deposition in Various Glomerular Diseases

Doi¹,

Kanatsu²,

Suehiro³

et al. 1987

Nephron

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The clinicopathological findings of isolated mesangial C3d deposition in the absence of other complement components or immunoglobulins are summarized. 55 out of 242 individual human renal biopsies examined by immunoperoxidase microscopy had isolated C3d deposition. This group consisted of 12 patients with chronic glomerulonephritis, 8 with minimal-change nephrotic syndrome, 32 with benign recurrent hematuria, 2 with Bartter’s syndrome and 1 with Raynaud’s syndrome. None of these patients had a disorder of the renal function and in all the patients the disease took a benign clinical course. Light-microscopic findings indicated injuries ranging from minor glomerular abnormality to mild diffuse mesangial proliferative glomerulonephritis, and there were no other remarkable findings such as cellular crescents, global sclerosis or interstitial infiltration. By immunoperoxidase microscopy, fine granular deposits of C3d were identified only in the mesangium, and arteriolar C3 staining was seen in 31 of the 55 patients. In 38 of the 42 patients examined by electron microscopy, electron-dense deposits were identified in the mesangial matrix. These findings suggest that isolated C3d deposition is a new entity with benign features both clinically and pathologically.

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“…One might question the role of complement activation in human MN because the non-complement-fixing IgG4 isotype predominates in the immune deposits (29,53), and the C1qr 2 s 2 complex is quite large (M r ϳ 800 kDa), which undoubtedly impedes its access to the subepithelial space. Still, there is a good deal of circumstantial evidence that complement is activated in subepithelial immune deposits, including the presence of C3 and C5b-9 in many cases (48,99) and C3d in all cases of human MN (28); C3d is the stable C3 product generated from iC3b by factor I, presumably relying on podocyte CR1 as a cofactor.…”

Section: Implications For Human Mnmentioning

confidence: 99%

Experimental membranous nephropathy redux

Cybulsky

Quigg²,

Salant³

2005

American Journal of Physiology-Renal Physiology

117

133

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Membranous nephropathy (MN) is a common cause of nephrotic syndrome in adults. Active and passive Heymann nephritis (HN) in rats are valuable experimental models because their features so closely resemble human MN. In HN, subepithelial immune deposits form in situ as a result of circulating antibodies. Complement activation leads to assembly of C5b-9 on glomerular epithelial cell (GEC) plasma membranes and is essential for sublethal GEC injury and the onset of proteinuria. This review revisits HN and focuses on areas of substantial progress in recent years. The response of the GEC to sublethal C5b-9 attack is not simply due to disruption of the plasma membrane but is due to the activation of specific signaling pathways. These include activation of protein kinases, phospholipases, cyclooxygenases, transcription factors, growth factors, NADPH oxidase, stress proteins, proteinases, and others. Ultimately, these signals impact on cell metabolic pathways and the structure/function of lipids and key proteins in the cytoskeleton and slit-diaphragm. Some signals affect GEC adversely. Thus C5b-9 induces partial dissolution of the actin cytoskeleton. There is a decline in nephrin expression, reduction in F-actin-bound nephrin, and loss of slit-diaphragm integrity. Other signals, such as endoplasmic reticulum stress, may limit complement-induced injury, or promote recovery. The extent of complement activation and GEC injury is dependent, in part, on complement-regulatory proteins, which act at early or late steps within the complement cascade. Identification of key steps in complement activation, the cellular signaling pathways, and the targets will facilitate therapeutic intervention in reversing GEC injury in human MN.

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Demonstration of C3d Deposits in Membranous Nephropathy

Cited by 54 publications

References 7 publications

Segmental Membranous Glomerulonephritis in Children

Segmental Membranous Glomerulonephritis in Children

Clinicopathological Study of Patients with Mesangial Isolated C3d Deposition in Various Glomerular Diseases

Experimental membranous nephropathy redux

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