Anti-factor B autoantibody in dense deposit disease

Strobel, Stefanie; Zimmering, Miriam; Papp, Krisztián; Prechl, József; Józsi, Mihály

doi:10.1016/j.molimm.2010.02.002

Cited by 98 publications

(80 citation statements)

References 39 publications

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“…The different phenotypes reflect antibody specificity for either the amino-or carboxy-terminal SCRs of FH, respectively. There has also been a single report describing a FBAA-positive DDD patient (44). In both that patient and the three FBAA-positive DDD patients in our study, the antibody also showed affinity for C3 convertase but not for other individual complement proteins.…”

Section: Discussionsupporting

confidence: 61%

Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

Zhang¹,

Meyer²,

Wang

et al. 2012

Clinical Journal of the American Society of Nephrology

171

160

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SummaryBackground and objectives This study was designed to investigate the causes of alternative pathway dysregulation in a cohort of patients with dense deposit disease (DDD).Design, setting, participants, & measurements Thirty-two patients with biopsy-proven DDD underwent screening for C3 nephritic factors (C3Nefs), factor H autoantibodies (FHAAs), factor B autoantibodies (FBAAs), and genetic variants in CFH. C3Nefs were detected by: ELISA, C3 convertase surface assay (C3CSA), C3CSA with properdin (C3CSAP), two-dimensional immunoelectrophoresis (2DIEP), and immunofixation electrophoresis (IFE). FHAAs and FBAAs were detected by ELISA, and CFH variants were identified by Sanger sequencing.Results Twenty-five patients (78%) were positive for C3Nefs. Three C3Nef-positive patients were also positive for FBAAs and one of these patients additionally carried two novel missense variants in CFH. Of the seven C3Nef-negative patients, one patient was positive for FHAAs and two patients carried CFH variants that may be causally related to their DDD phenotype. C3CASP was the most sensitive C3Nef-detection assay. C3CASP and IFE are complementary because C3CSAP measures the stabilizing properties of C3Nefs, whereas IFE measures their expected consequence-breakdown of C3b.Conclusions A test panel that includes C3CSAP, IFE, FHAAs, FBAAs, and genetic testing for CFH variants will identify a probable cause for alternative pathway dysregulation in approximately 90% of DDD patients. Dysregulation is most frequently due to C3Nefs, although some patients test positive for FHAAs, FBAAs, and CFH mutations. Defining the pathophysiology of DDD should facilitate the development of mechanism-directed therapies.

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Section: Discussionsupporting

confidence: 61%

Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

Zhang¹,

Meyer²,

Wang

et al. 2012

Clinical Journal of the American Society of Nephrology

171

160

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“…Acquired dysregulation of the alternative pathway due to neutralizing autoantibodies against CFH [20] has also been described. Recently, an autoantibody to factor B, an activation protein within the alternative pathway, has also been associated with MPGN [21]. In summary factors that increase alternative pathway activation h a v e b e e n a s s o c i a t e d w i t h M P G N i n w h i c h there is glomerular C3 with little or no immunoglobulin.…”

Section: Complement and Mpgnmentioning

confidence: 99%

Membranoproliferative Glomerulonephritis

Matthew¹,

Joshua²

2011

An Update on Glomerulopathies - Clinical and Treatment Aspects

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“…Autoantibodies may be directed against the complementregulating factors, such as factor H, factor I, factor B as well as against C3 convertase itself [55,56] . The first described autoantibody was the C3 ne phritic factor (C3 NeF), which binds and stabilizes C3 convertase [57] .…”

Section: Pathophysiologymentioning

confidence: 99%

Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN

Salvadori¹,

Rosso²

2016

WJN

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This review revises the reclassification of the membranoproliferative glomerulonephritis (MPGN) after the consensus conference that by 2015 reclassified all the glomerulonephritis basing on etiology and pathogenesis, instead of the histomorphological aspects. After reclassification, two types of MPGN are to date recognized: The immunocomplexes mediated MPGN and the complement mediated MPGN. The latter type is more extensively described in the review either because several of these entities are completely new or because the improved knowledge of the complement cascade allowed for new diagnostic and therapeutic approaches. Overall the complement mediated MPGN are related to acquired or genetic cause. The presence of circulating auto antibodies is the principal acquired cause. Genetic wide association studies and family studies allowed to recognize genetic mutations of different types as causes of the complement dysregulation. The complement cascade is a complex phenomenon and activating factors and regulating factors should be distinguished. Genetic mutations causing abnormalities either in activating or in regulating factors have been described. The diagnosis of the complement mediated MPGN requires a complete study of all these different complement factors. As a consequence, new therapeutic approaches are becoming available. Indeed, in addition to a nonspecific treatment and to the immunosuppression that has the aim to block the auto antibodies production, the specific inhibition of complement activation is relatively new and may act either blocking the C5 convertase or the C3 convertase. The drugs acting on C3 convertase are still in different phases of clinical development and might represent drugs for the future. Overall the authors consider that one of the principal problems in finding new types of drugs are both the rarity of the disease and the consequent poor interest in the marketing and the lack of large international cooperative studies.

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Anti-factor B autoantibody in dense deposit disease

Cited by 98 publications

References 39 publications

Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

Causes of Alternative Pathway Dysregulation in Dense Deposit Disease

Membranoproliferative Glomerulonephritis

Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN

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