Phospholipase A2 Receptor–Related Membranous Nephropathy and Mannan-Binding Lectin Deficiency

Bally, Stéphane; Dębiec, Hanna; Ponard, D.; Dijoud, Frédérique; Rendu, John; Fauré, Julien; Ronco, Pierre; Dumestre-Pérard, Chantal

doi:10.1681/asn.2015101155

Cited by 89 publications

(82 citation statements)

References 35 publications

(40 reference statements)

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“…In a study comparing 21 membranous patients with 19 patients with minimal change disease (MCD), capillary C4d deposition (via IHC) was present in 100% of membranous patients and in none of the MCD patients [37]. Bally et al [38] report a case of IMN in a patient with deficiency of MBL in whom complement activation was thought to occur via AP activation; they further evaluated 77 patients with idiopathic MN, and found similar MBL deficiency in 4 patients in whom there was weak C4d staining. However, all remaining patients with intact MBL had intense C4d staining (via IF) along glomerular capillary wall indicating activation via LP.…”

Section: Membranous Nephropathymentioning

confidence: 99%

C4d in Native Glomerular Diseases

Chandra¹

2019

Am J Nephrol

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Complement activation occurs in many glomerular diseases, the exact pathway(s) of activation has been studied in detail in some diseases but not in all. C4d is generated by the activation of classical and lectin pathways, and its presence can point to the activation of either of these pathways. This review aims to summarize the available data with regard to the deposition of glomerular C4d in native kidney biopsies in different glomerular pathologies that may be useful for future research into the role of complement activation in glomerular diseases. While there is more information on C4d in certain diseases (e.g., Immunoglobulin A (IgA) nephropathy), there is scant data in other diseases (such as focal segmental glomerulosclerosis).

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Section: Membranous Nephropathymentioning

confidence: 99%

C4d in Native Glomerular Diseases

Chandra¹

2019

Am J Nephrol

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“…Although immune complexes mainly activate complement via the classical pathway, glomerular deposition of factor B and properdin also occurs in membranous nephropathy [108, 109], lupus nephritis [110], and anti-GBM antibody disease [111], indicative of the alternative pathway activation. These findings suggest insufficient complement regulation by factor H, which may be exacerbated by the loss of GBM heparan sulfate, as depicted in Figure 3.…”

Section: The Role Of Gbm Heparan Sulfate Chains In Local Complemenmentioning

confidence: 99%

Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation

Borza

2017

Matrix Biology

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The glomerular basement membrane (GBM) is an essential component of the glomerular filtration barrier. Heparan sulfate proteoglycans such as agrin are major components of the GBM, along with α345(IV) collagen, laminin-521 and nidogen. A loss of GBM heparan sulfate chains is associated with proteinuria in several glomerular diseases and may contribute to the underlying pathology. As the major determinants of the anionic charge of the GBM, heparan sulfate chains have been thought to impart charge selectivity to the glomerular filtration, a view challenged by the negligible albuminuria in mice that lack heparan sulfate in the GBM. Recent studies provide increasing evidence that heparan sulfate chains modulate local complement activation by recruiting complement regulatory protein factor H, the major inhibitor of the alternative pathway in plasma. Factor H selectively inactivates C3b bound to surfaces bearing host-specific polyanions such as heparan sulfate, thus limiting complement activation on self surfaces such as the GBM, which are not protected by cell-bound complement regulators. We discuss mechanisms whereby the acquired loss of GBM heparan sulfate can impair the local regulation of the alternative pathway, exacerbating complement activation and glomerular injury in immune-mediated kidney diseases such as membranous nephropathy and lupus nephritis.

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“…In the present study, genotype O/O, previously related to a 2.6-fold greater risk of developing LN [20], was not encountered in any of the patients. Only Bally et al [21] have evaluated the presence of MBL2 polymorphism in IMN. The authors reported that 5 out of 78 patients presented genotypes associated with low serum levels of MBL; however, there was no comparison group.…”

Section: Resultsmentioning

confidence: 99%

“…It is known that IMN occurs in genetically susceptible individuals; however, very few studies have investigated the possible relationship between this glomerulopathy and polymorphisms of the MBL2 gene, which is responsible for producing MBL [15][16][17][18]. Although lupus nephritis is associated with genetic variants of MBL2 and the consequent deficient production of the MBL protein [19,20], only Bally et al [21] have evaluated the sequencing of the MBL2 gene in IMN, and found polymorphisms in 5 out of 78 patients. This gene is responsible for producing the amino acid sequences of the collagen triple helix of the MBL2 [22].…”

Section: Introductionmentioning

confidence: 99%

<b><i>Mannose-Binding Lectin2</i></b> Gene Polymorphism and IgG4 in Membranous Nephropathy

Costa¹,

Valente²,

Vajgel³

et al. 2018

Nephron

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Background: Idiopathic membranous nephropathy (IMN) has been linked to the lectin pathway, IgG4 and genetic susceptibility. We investigated the frequency of mannose-binding lectin2 (MBL2) gene polymorphisms and the serum ratio of IgG4 in patients with membranous nephropathy (MN). Methods: Polymorphisms in the exon 1 of the MBL2 gene (codons 52, 54, and 57) and single base polymorphisms at positions -550 (HL) and -221 (XY) in the promoter region were evaluated in 60 patients compared to a control group (CG) of 101 blood donors. It established the frequency of polymorphisms and the serum ratio of IgG4 comparing 2 etiologies of MN: idiopathic (35 patients) and secondary to systemic lupus erythematosus (25 patients). Results: Patients with MN had a 2.54-fold higher probability (95% CI 1.51-4.31) of carrying the O alelle, exon 1 variant, and 11.16-fold higher probability (95% CI 4.77-28.41) of having A/O genotype when compared to CG. The frequency of polymorphisms in the promoter region was similar between the groups. Combined genotypes generally related to the defective production of MBL (YA/O, XA/O and O/O) were more frequent in patients with MN (OR 7.11;), when compared to controls. The median of serum ratio IgG4 was 5% for idiopathic MN and 3% for lupus MN patients (p = 0.016). Conclusions: Our data suggests that MBL2 polymorphisms may be associated with the activation of the lectin pathway by IgG4 subclass antibodies in MN.

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Phospholipase A2 Receptor–Related Membranous Nephropathy and Mannan-Binding Lectin Deficiency

Cited by 89 publications

References 35 publications

C4d in Native Glomerular Diseases

C4d in Native Glomerular Diseases

Glomerular basement membrane heparan sulfate in health and disease: A regulator of local complement activation

<b><i>Mannose-Binding Lectin2</i></b> Gene Polymorphism and IgG4 in Membranous Nephropathy

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