ArticleClinical and experimental immunology2002
Coupling complement regulators to immunoglobulin domains generates effective anti-complement reagents with extended half-life in vivo.
Article in Clinical and experimental immunology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 49 citations in OpenAlex.
- Therapeutic Efficacy of aFrontiers in microbiology · 2020Article
- Modulation of PBMC-decay accelerating factor (PBMC-DAF) and cytokines in rheumatoid arthritis.Molecular and cellular biochemistry · 2016Article
- Expression of an engineered soluble coxsackievirus and adenovirus receptor by a dimeric AAV9 vector inhibits adenovirus infection in mice.Gene therapy · 2015Article
- Functional analysis of a complement polymorphism (rs17611) associated with rheumatoid arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
- Sensitive and specific assays for C3 nephritic factors clarify mechanisms underlying complement dysregulation.Kidney international · 2012Article
- Protective effect of scFv-DAF fusion protein on the complement attack to acetylcholine receptor: a possible option for treatment of myasthenia gravis.Muscle & nerve · 2012Article
- Pharmacological and biological antiviral therapeutics for cardiac coxsackievirus infections.Molecules (Basel, Switzerland) · 2011Review
- Upregulating CD59: a new strategy for protection of neurons from complement-mediated degeneration.The pharmacogenomics journal · 2010Article
- Therapeutic potential of complement modulation.Nature reviews. Drug discovery · 2010Review
- Hepatic inflammation mediated by hepatitis C virus core protein is ameliorated by blocking complement activation.BMC medical genomics · 2009Article
- Implication of complement system and its regulators in Alzheimer's disease.Current neuropharmacology · 2009Article
- Anticomplement therapy.Biologics : targets & therapy · 2008Article
- Prevention of experimental autoimmune myasthenia gravis by rat Crry-Ig: A model agent for long-term complement inhibition in vivo.Molecular immunology · 2008Article
- Statin-induced expression of CD59 on vascular endothelium in hypoxia: a potential mechanism for the anti-inflammatory actions of statins in rheumatoid arthritis.Arthritis research & therapy · 2006Article
- Biological activity, membrane-targeting modification, and crystallization of soluble human decay accelerating factor expressed in E. coli.Protein science : a publication of the Protein Society · 2004Article
- Nontransgenic hyperexpression of a complement regulator in donor kidney modulates transplant ischemia/reperfusion damage, acute rejection, and chronic nephropathy.The American journal of pathology · 2003Article
- Neuronal death in Alzheimer's disease and therapeutic opportunities.Journal of cellular and molecular medicineReview
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Complement activation and subsequent generation of inflammatory molecules and membrane attack complex contributes to the pathology of a number of inflammatory and degenerative diseases, including arthritis, glomerulonephritis and demyelination. Agents that specifically inhibit complement activation might prove beneficial in the treatment of these diseases. Soluble recombinant forms of the naturally occurring membrane complement regulatory proteins (CRP) have been exploited for this purpose. We have undertaken to design better therapeutics based on CRP. Here we describe the generation of soluble, recombinant CRP comprising rat decay accelerating factor (DAF) or rat CD59 expressed as Fc fusion proteins, antibody-like molecules comprising two CRP moieties in place of the antibody Fab arms (CRP-Ig). Reagents bearing DAF on each arm (DAF-Ig), CD59 on each arm (CD59-Ig) and a hybrid reagent containing both DAF and CD59 were generated. All three reagents inhibited C activation in vitro. Compared with soluble CRP lacking Fc domains, activity was reduced, but was fully restored by enzymatic release of the regulator from the Ig moiety, implicating steric constraints in reducing functional activity. In vivo studies showed that DAF-Ig, when compared to soluble DAF, had a much extended half-life in the circulation in rats and concomitantly caused a sustained reduction in plasma complement activity. When given intra-articularly to rats in a model of arthritis, DAF-Ig significantly reduced severity of disease. The data demonstrate the potential of CRP-Ig as reagents for sustained therapy of inflammatory disorders, including arthritis, but emphasize the need for careful design of fusion proteins to retain function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.