ArticleJournal of immunology (Baltimore, Md. : 1950)2014
A humanized antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- The complement alternative pathway in paroxysmal nocturnal hemoglobinuria: From a pathogenic mechanism to a therapeutic target.Immunological reviews · 2023Review
- Discovery of APL-1030, a Novel, High-Affinity Nanofitin Inhibitor of C3-Mediated Complement Activation.Biomolecules · 2022Article
- Novel Selection Approaches to Identify Antibodies Targeting Neoepitopes on the C5b6 Intermediate Complex to Inhibit Membrane Attack Complex Formation.Antibodies (Basel, Switzerland) · 2021Article
- Inhibition of the Complement Alternative Pathway by Chemically Modified DNA Aptamers That Bind with Picomolar Affinity to Factor B.Journal of immunology (Baltimore, Md. : 1950) · 2021Article
- A Narrative Review on C3 Glomerulopathy: A Rare Renal Disease.International journal of molecular sciences · 2020Review
- [How I diagnose and treat paroxysmal nocturnal hemoglobinuria].Zhonghua xue ye xue za zhi = Zhonghua xueyexue zazhi · 2018Article
- Complement-mediated renal diseases after kidney transplantation - current diagnostic and therapeutic options inWorld journal of transplantation · 2018Review
- Thrombotic microangiopathy after renal transplantation: Current insights inWorld journal of transplantation · 2018Review
- Expanding horizons in complement drug discovery: challenges and emerging strategies.Seminars in immunopathology · 2018Review
- Complement in ANCA-associated vasculitis: mechanisms and implications for management.Nature reviews. Nephrology · 2017Review
- Complement related kidney diseases: Recurrence after transplantation.World journal of transplantation · 2016Review
- Complement-Mediated Glomerular Diseases: A Tale of 3 Pathways.Kidney international reports · 2016Review
- Reclassification of membranoproliferative glomerulonephritis: Identification of a new GN: C3GN.World journal of nephrology · 2016Review
- Therapeutic control of complement activation at the level of the central component C3.Immunobiology · 2016Review
- New milestones ahead in complement-targeted therapy.Seminars in immunology · 2016Review
- Complement, a target for therapy in inflammatory and degenerative diseases.Nature reviews. Drug discovery · 2015Review
- Kidney Disease Caused by Dysregulation of the Complement Alternative Pathway: An Etiologic Approach.Journal of the American Society of Nephrology : JASN · 2015Review
- Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy.Immunobiology · 2015Article
- Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape.Expert review of hematology · 2014Review
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Authors and funding
8 authors.
Funding
Abstract
Dysregulation of the complement alternative pathway can cause disease in various organs that may be life-threatening. Severe alternative pathway dysregulation can be triggered by autoantibodies to the C3 convertase, termed nephritic factors, which cause pathological stabilization of the convertase enzyme and confer resistance to innate control mechanisms; unregulated complement consumption followed by deposition of C3 fragments in tissues ensues. The mAb, 3E7, and its humanized derivative, H17, have been shown previously to specifically bind activated C3 and prevent binding of both the activating protein, factor B, and the inhibitor, factor H, which are opposite effects that complicate its potential for therapy. Using ligand binding assays, functional assays, and electron microscopy, we show that these Abs bind C3b via a site that overlaps the binding site on C3 for the Ba domain within factor B, thereby blocking an interaction essential for convertase formation. Both Abs also bind the preformed convertase, C3bBb, and provide powerful inhibition of complement activation by preventing cleavage of C3. Critically, the Abs also bound and inhibited C3 cleavage by the nephritic factor-stabilized convertase. We suggest that by preventing enzyme formation and/or cleavage of C3 to its active downstream fragments, H17 may be an effective therapy for conditions caused by severe dysregulation of the C3 convertase and, in particular, those that involve nephritic factors, such as dense deposit disease.
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Registered trials
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