ArticleThe Journal of clinical investigation2014
Complement factor H-related hybrid protein deregulates complement in dense deposit disease.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers.
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Who cites it
62 citing papers in PubMed, 108 citations in OpenAlex.
- C3 glomerulopathy: a kidney disease mediated by alternative pathway deregulation.Frontiers in nephrology · 2024Review
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- CFH-CFHR1 hybrid genes in two cases of atypical hemolytic uremic syndrome.Journal of human genetics · 2023Article
- Increased plasma level of terminal complement complex in AMD patients: potential functional consequences for RPE cells.Frontiers in immunology · 2023Article
- The Factor H protein family: The switchers of the complement alternative pathway.Immunological reviews · 2023Review
- Genetic variability shapes the alternative pathway complement activity and predisposition to complement-related diseases.Immunological reviews · 2023Review
- C3 glomerulopathies: dense deposit disease and C3 glomerulonephritis.Frontiers in medicine · 2023Review
- A clinical approach to children with C3 glomerulopathy.Pediatric nephrology (Berlin, Germany) · 2022Review
- An Interdisciplinary Diagnostic Approach to Guide Therapy in C3 Glomerulopathy.Frontiers in immunology · 2022Article
- Case report: Novel FHR2 variants in atypical Hemolytic Uremic Syndrome: A case study of a translational medicine approach in renal transplantation.Frontiers in immunology · 2022Article
- Complement Factor H-Related Proteins FHR1 and FHR5 Interact With Extracellular Matrix Ligands, Reduce Factor H Regulatory Activity and Enhance Complement Activation.Frontiers in immunology · 2022Article
- Gain-of-function factor H-related 5 protein impairs glomerular complement regulation resulting in kidney damage.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Article
- A Family Affair: Addressing the Challenges of Factor H and the Related Proteins.Frontiers in immunology · 2021Review
- Detection of Genetic Rearrangements in the Regulators of Complement Activation RCA Cluster by High-Throughput Sequencing and MLPA.Methods in molecular biology (Clifton, N.J.) · 2021Article
- The solution structure of the complement deregulator FHR5 reveals a compact dimer and provides new insights into CFHR5 nephropathy.The Journal of biological chemistry · 2020Article
- Review
- Large-Scale Whole-Genome Sequencing Reveals the Genetic Architecture of Primary Membranoproliferative GN and C3 Glomerulopathy.Journal of the American Society of Nephrology : JASN · 2020Article
- Interaction of the Factor H Family Proteins FHR-1 and FHR-5 With DNA and Dead Cells: Implications for the Regulation of Complement Activation and Opsonization.Frontiers in immunology · 2020Article
- Complement and Complement Targeting Therapies in Glomerular Diseases.International journal of molecular sciences · 2019Review
2 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The renal disorder C3 glomerulopathy with dense deposit disease (C3G-DDD) pattern results from complement dysfunction and primarily affects children and young adults. There is no effective treatment, and patients often progress to end-stage renal failure. A small fraction of C3G-DDD cases linked to factor H or C3 gene mutations as well as autoantibodies have been reported. Here, we examined an index family with 2 patients with C3G-DDD and identified a chromosomal deletion in the complement factor H-related (CFHR) gene cluster. This deletion resulted in expression of a hybrid CFHR2-CFHR5 plasma protein. The recombinant hybrid protein stabilized the C3 convertase and reduced factor H-mediated convertase decay. One patient was refractory to plasma replacement and exchange therapy, as evidenced by the hybrid protein quickly returning to pretreatment plasma levels. Subsequently, complement inhibitors were tested on serum from the patient for their ability to block activity of CFHR2-CFHR5. Soluble CR1 restored defective C3 convertase regulation; however, neither eculizumab nor tagged compstatin had any effect. Our findings provide insight into the importance of CFHR proteins for C3 convertase regulation and identify a genetic variation in the CFHR gene cluster that promotes C3G-DDD. Monitoring copy number and sequence variations in the CFHR gene cluster in C3G-DDD and kidney patients with C3G-DDD variations will help guide treatment strategies.
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