C3 nephritic factor can be associated with membranous glomerulonephritis

Niel, Olivier; Dallocchio, A.; Thouret, Marie-Christine; Guigonis, Vincent; Cassuto, Élisabeth; Frémeaux‐Bacchi, Véronique; Bérard, Étienne

doi:10.1007/s00467-014-3004-3

Cited by 5 publications

(5 citation statements)

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“…Pathological results play decisive role in the diagnosis of nephropathy, by which kidney diseases are classified. Primary IgA nephropathy is characterized with IgA-dominant deposition in the glomerulus [ 12 ]; in MN, the pathological characteristics is IgG-dominant deposits [ 13 ] mostly with C3 deposits [ 14 ], and IgM or IgA has also been reported in MN [ 15 , 16 ]; normally, less immonoprotein depositions are found in the patients with MCD [ 17 ]; few researches find that IgA, IgM, C3 or C1q immune complex could also exist in MCD [ 18 – 20 ].…”

Section: Discussionmentioning

confidence: 99%

A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis

et al. 2018

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BackgroundImmunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and minimal-change disease (MCD) are three common types of glomerulonephritis in China. Pathological diagnosis based on renal biopsy is the criterion and the golden standard for diagnosing the sub-types of primary or secondary glomerulonephritis. Immunoglobulin and complements might be used in the differential diagnosis of glomerulonephritis without renal biopsies. However, the relationship between IF intensities of immune proteins and the corresponding serum levels remained unclear, and seldom studies combine histopathological examination results and blood tests together for a predictive purpose. This study was considered as a pilot study for integrating histopathological indicators into serum parameters for exploring the relationship of IF intensity and serum values of immunoglobulin and complement, and for screening and investigating effective indicators inIgAN, MN and MCD.MethodsRenal tissue immunofluorescence (IF) intensity grades and serum levels of immunoglobulin and complements (IgG, IgA, IgM, C3 and C4) were retrospectively analyzed in 236 cases with IgAN, MN or MCD. IF grades were grouped as negative (−), positive (+) or strong positive (++) with both high and low magnification of microscope. Other serum indicators such as urea nitrogen (BUN), creatinine (Crea) and estimated glomerular filtration rate (eGFR) were also evaluated among the groups.ResultsThere were difference in IgA, IgG and C3 IF intensity grades among IgAN, MN and MCD groups (p = 9.82E-43, 4.60E-39, 7.45E-15, respectively). Serum values of BUN, Crea, eGFR, IgG, IgA, IgM and C4 showed difference in three groups (BUN: p = 0.045, Crea: p = 3.45E-5, eGFR: p = 0.005, IgG: p = 1.68E-14, IgA: p = 9.14E-9, IgM: p = 0.014, C4: p = 0.026). eGFR had the trend to decrease with enhanced IgA IF positive grades (p = 8.99E-4); Crea had trends to decrease with both enhanced IgA and IgG IF intensity grades (p = 2.06E-6, 2.94E-5, respectively). In all subjects, serum IgA levels was inversely correlated with eGFR(r = − 0.216, p = 0.001) and correlated with Crea levels(r = 0.189, p = 0.004); serum IgG and Crea showed no correlation which were discordance with inverse correlation of IgG IF grade and Crea(r = 0.058,p = 0.379). IgG serum level was inverse correlated with its IF grades (p = 3.54E-5, p = 7.08E-6, respectively); C3 serum levels had significantly difference between Neg and positive (+) group (p = 0.0003). IgA serum level was positive correlated with its IF grades (Neg-(+): p = 0.0001; (+)-(++): p = 0.022; Neg-(++): p = 2.01E-10). After matching comparison among C3 groups, C3 Neg. group and C3 ++ group had difference (*p = 0.017). C4 had all negative IF expression in all pathological groups. In IgAN subjects, there were statistical differences of serum C3 levels between its pathological Neg and positive (+) group(p = 0.026), and serum IgA levels showed difference between IgA pathological positive(+) and (++)(p = 0.007). In MN subjects, sIgG levels showed difference between Ig...

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Section: Discussionmentioning

confidence: 99%

A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis

et al. 2018

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“…In fact, a patient with PMN and complete C4 deficiency has been reported, implicating that the disease may develop without the LP activation [146]. The prevalence of the C3Nef (Table 2) with low C3 levels has also been described in a case report of two unrelated children with PMN [147]. Also, another study reported the loss of glomerular heparan sulfate proteoglycans from the GBM, which bind CFH, causing local dysregulation of the AP [143].…”

Section: Primary Membranous Nephropathymentioning

confidence: 90%

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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“…Although C3NeFs are closely linked with C3G, they have been detected in healthy individuals, suggesting that this autoantibody is part of the normal immune repertoire (73, 74). Therefore, a fundamental unanswered question is whether C3NeF is the cause of the disease, or whether C3NeF is a consequence of the disease process that then acts exacerbating the disease pathology (17, 74, 75). Moreover, plasma C3 consumption and disease severity do not always correlate with the presence and activity of C3NeF (76–78).…”

Section: Clinical Associationsmentioning

confidence: 99%

“…Immunosuppressive Therapy: These treatments are focused to limit and/or reduce the production of NFs, and they have mainly been proved in patients with C3G and MPGN. The benefit of long-term alternate-day steroid therapy for idiopathic MPGN has been suggested; however, these studies include a combination of patients with different types of MPGN, limiting possible conclusions (75, 146, 147). An interesting report from the Spanish Group for Glomerular Disease Study showed the effectiveness of the combination of mycophenolate mofetil (MMF) and glucocorticoids in patients with C3GN (148).…”

Section: Management and Therapeutic Perspectives For Patients With Nementioning

confidence: 99%

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations

et al. 2019

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Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephritic factor has been characterized by the ability to stabilize C5 convertase of the alternative pathway (C5NeF). In addition, there are autoantibodies against assembled C3/C5 convertase of the classical and lectin pathways (C4NeF). These autoantibodies have been mainly associated with kidney diseases, like C3 glomerulopathy and immune complex-associated-membranoproliferative glomerulonephritis. Other clinical situations where these autoantibodies have been observed include infections and autoimmune disorders such as systemic lupus erythematosus and acquired partial lipodystrophy. C3 hypocomplementemia is a common finding in all patients with nephritic factors. The methods to measure nephritic factors are not standardized, technically complex, and lack of an appropriate quality control. This review will be focused in the description of the mechanism of action of the three known nephritic factors (C3NeF, C4NeF, and C5NeF), and their association with human diseases. Moreover, we present an overview regarding the diagnostic tools for its detection, and the main therapeutic approach for the patients with nephritic factors.

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C3 nephritic factor can be associated with membranous glomerulonephritis

Abstract: C3NeF can be associated with membranous glomerulonephritis in children. Clinical presentation is mild, and mid-term outcome is favourable under adequate therapy. However, complement anomalies persist for several years.

Cited by 5 publications

References 7 publications

A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis

A pilot and comparative study between pathological and serological levels of immunoglobulin and complement among three kinds of primary glomerulonephritis

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

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations

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