ArticleBlood2021
Functional characterization of 105 factor H variants associated with aHUS: lessons for variant classification.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 55 citations in OpenAlex.
- Association of Complement Genetics with Outcomes in IgA Nephropathy.Clinical journal of the American Society of Nephrology : CJASN · 2026Article
- Thrombotic microangiopathy after kidney transplantation: diagnosis and management strategies.Clinical kidney journal · 2026Review
- Recurrence of C3 Glomerulopathy and Immune Complex-Mediated Membranoproliferative Glomerulonephritis After Kidney Transplantation: Challenges and Opportunities.Kidney international reports · 2026Review
- Atypical hemolytic uremic syndrome in a patient with thalassemia and a CFH gene mutation: a case report.Frontiers in medicine · 2026Article
- Approach to the prevention of atypical hemolytic uremic syndrome recurrence using eculizumab in a pregnant kidney transplant recipient with complement factor H gene mutation: a case report and literature review.Journal of nephrology · 2025Review
- Atypical Hemolytic Uremic Syndrome: A Review of Complement Dysregulation, Genetic Susceptibility and Multiorgan Involvement.Journal of clinical medicine · 2025Review
- Functional characterisation of missense ceruloplasmin variants and real-world prevalence assessment of Aceruloplasminemia using population data.EBioMedicine · 2025Article
- Complement-mediated HUS revisited: evolving insights into pathophysiology, diagnosis, and treatment.Frontiers in immunology · 2025Review
- Effective long-term treatment with moss-produced factor H by overcoming the antibody response in a mouse model of C3G.Frontiers in immunology · 2025Article
- Article
- Atypical hemolytic uremic syndrome: diagnosis, management, and discontinuation of therapy.Hematology. American Society of Hematology. Education Program · 2024Review
- Complement or insult: the emerging link between complement cascade deficiencies and pathology of myeloid malignancies.Journal of leukocyte biology · 2024Review
- Anti-C5 monoclonal antibody treatment showing pathological resolution of complement-mediated atypical hemolytic uremic syndrome: a case report.BMC nephrology · 2024Article
- Complement Activation in Nephrotic Glomerular Diseases.Biomedicines · 2024Review
- Moss-produced human complement factor H with modified glycans has an extended half-life and improved biological activity.Frontiers in immunology · 2024Article
- The human factor H protein family - an update.Frontiers in immunology · 2024Review
- The role of complement in kidney disease.Nature reviews. Nephrology · 2023Review
- Underlying Genetics of aHUS: Which Connection with Outcome and Treatment Discontinuation?International journal of molecular sciences · 2023Review
- Complement gene variant effect on relapse of complement-mediated thrombotic microangiopathy after eculizumab cessation.Blood advances · 2023Article
- AnFrontiers in immunology · 2023Article
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy that can progress, when untreated, to end-stage renal disease. Most frequently, aHUS is caused by complement dysregulation due to pathogenic variants in genes that encode complement components and regulators. Among these genes, the factor H (FH) gene, CFH, presents with the highest frequency (15% to 20%) of variants and is associated with the poorest prognosis. Correct classification of CFH variants as pathogenic or benign is essential to clinical care but remains challenging owing to the dearth of functional studies. As a result, significant numbers of variants are reported as variants of uncertain significance. To address this knowledge gap, we expressed and functionally characterized 105 aHUS-associated FH variants. All FH variants were categorized as pathogenic or benign and, for each, we fully documented the nature of the pathogenicity. Twenty-six previously characterized FH variants were used as controls to validate and confirm the robustness of the functional assays used. Of the remaining 79 uncharacterized variants, only 29 (36.7%) alter FH expression or function in vitro and, therefore, are proposed to be pathogenic. We show that rarity in control databases is not informative for variant classification, and we identify important limitations in applying prediction algorithms to FH variants. Based on structural and functional data, we suggest ways to circumvent these difficulties and, thereby, improve variant classification. Our work highlights the need for functional assays to interpret FH variants accurately if clinical care of patients with aHUS is to be individualized and optimized.
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