Novel factor H mutation associated with familial membranoproliferative glomerulonephritis type I

Alfandary, Hadas; Davidovits, Miriam

doi:10.1007/s00467-015-3166-7

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…Two patients with homozygous CFH deficiency, the main regulatory protein of AP, have been diagnosed with Ig-MPGN. 10,11 C3Nef was positive in 50% of patients in two large Ig-MPGN cohorts. 4,12 Applying the current histopathologic definition of MPGN, ten of 14 patients in our series with available biopsy specimens were diagnosed as Ig-MPGN, because the C3 intensity of the staining evaluated by IF was identical to the other immune reactants.…”

Section: Discussionmentioning

confidence: 96%

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Marinozzi

Roumenina

Chauvet

et al. 2017

JASN

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In C3 glomerulopathy (C3G), the alternative pathway of complement is frequently overactivated by autoantibodies that stabilize the C3 convertase C3bBb. Anti-C3b and anti-factor B (anti-FB) IgG have been reported in three patients with C3G. We screened a cohort of 141 patients with C3G and Ig-associated membranoproliferative GN (Ig-MPGN) for anti-FB and anti-C3b autoantibodies using ELISA. We identified seven patients with anti-FB IgG, three patients with anti-C3b IgG, and five patients with anti-FB and anti-C3b IgG. Of these 15 patients, ten were diagnosed with Ig-MPGN. Among those patients with available data, 92% had a nephrotic syndrome, 64% had AKI, and 67% had a documented infection. Patients negative for anti-C3b and anti-FB IgG had much lower rates of infection (17 [25%] patients with C3G and one [10%] patient with Ig-MPGN). After 48 months, four of 15 (26%) positive patients had developed ESRD or died. All 15 patients had high plasma Bb levels, six (40%) patients had low levels of C3, and nine (60%) patients had high levels of soluble C5b9. , IgG purified from patients with anti-FB Abs selectively enhanced C3 convertase activity; IgG from patients with anti-C3b/anti-FB Abs enhanced C3 and C5 cleavage. IgG from patients with anti-C3b Abs stabilized C3bBb and perturbed C3b binding to complement receptor 1 but did not perturb binding to factor H. In conclusion, the prevalence of anti-C3b/anti-FB Abs and alternative pathway activation is similar in Ig-MPGN and C3G, suggesting similar pathogenic mechanisms. Identification of the underlying defect in Ig-MPGN could lead to improved treatment.

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Section: Discussionmentioning

confidence: 96%

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Marinozzi

Roumenina

Chauvet

et al. 2017

JASN

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“…In contrast, because viral, bacterial, and protozoal infections are a common cause of immune-complex MPGN, it is thought that this might be a reason why MPGN is more common in developing countries (Cook and Pickering 2015 disease mechanism, recent studies have shown mutations also affecting the alternative pathway (AP) regulatory proteins and C3 nephritic factor (C3NeF)an autoantibody that stabilizes the AP C3 convertase. These findings suggest that the alternative pathway itself could also play an active role in MPGN type I pathogenesis (Alfandary and Davidovits 2015;Dragon-Durey 2004;Iatropoulos et al 2016;Leroy et al 2011;Servais et al 2012;Radhakrishnan et al 2012).…”

Section: Epidemiologymentioning

confidence: 81%

“…Genetic causes of complement abnormalities, such as CFH and CFI mutations, have been described in various case reports. Further, a genetic abnormality in the AP was identified in more than 50% of a French cohort with MPGN type I (Servais et al 2011;Servais et al 2012;Radhakrishnan et al 2012;Alfandary and Davidovits 2015;Dragon-Durey 2004). Further studies are required to determine the extent to which AP dysregulation contributes to immune-complex-mediated MPGN.…”

Section: Epidemiologymentioning

confidence: 99%

Membranoproliferative Glomerulonephritis, Type 1, Pediatric

Viteri

Reid-Adam

2017

Glomerulonephritis

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Membranoproliferative glomerulonephritis (MPGN) Type I is most common among a group of rare glomerular diseases historically classified according to findings on electron microscopy, and is characterized by subendothelial immune deposits. Most of what was traditionally characterized as MPGN type I falls under the category of immune complexmediated MPGN, while fewer cases of MPGN type I may be attributed to complement dysregulation. In children, MPGN type I is associated with approximately 1.3% of end stage kidney disease (ESKD) patients. Hypocomplementemia, hematuria and proteinuria are common at presentation, with nephrotic syndrome in MPGN associated with a worse prognosis. While there have been various approaches to treatment of MPGN type I in children, the mainstay of therapy is alternate day prednisone.

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Membranoproliferative Glomerulonephritis, Type 1, Pediatric

Viteri¹,

Reid-Adam²

2019

Glomerulonephritis

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Novel factor H mutation associated with familial membranoproliferative glomerulonephritis type I

Cited by 6 publications

References 26 publications

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Anti-Factor B and Anti-C3b Autoantibodies in C3 Glomerulopathy and Ig-Associated Membranoproliferative GN

Membranoproliferative Glomerulonephritis, Type 1, Pediatric

Membranoproliferative Glomerulonephritis, Type 1, Pediatric

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