ArticleJCI insight2018
Germline mutations in the alternative pathway of complement predispose to HELLP syndrome.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 87 citations in OpenAlex.
- Therapeutic plasma exchange in severe postpartum HELLP syndrome: a promising treatment.BMC pregnancy and childbirth · 2025Article
- Update in the diagnosis of complement-mediated thrombotic microangiopathy/atypical hemolytic uremic syndrome.Hematology. American Society of Hematology. Education Program · 2025Review
- Endothelial Glycocalyx: The Missing Link Between Angiogenic Imbalance in Preeclampsia and Systemic Inflammation in HELLP Syndrome.Comprehensive Physiology · 2025Review
- Exploring novel molecular mechanisms underlying recurrent pregnancy loss in decidual tissues.Scientific reports · 2025Article
- Genetic Susceptibility in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease: A Case-Control Study.International journal of molecular sciences · 2025Article
- Complement C5 inhibition in early onset HELLP syndrome.Blood advances · 2025Article
- The complement system in human pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- The role of complement in normal pregnancy and preeclampsia.Frontiers in immunology · 2025Review
- Prospective study of complement activation and thromboinflammation within sickle cell disease and its complications.HemaSphere · 2024Article
- Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.Journal of personalized medicine · 2024Article
- Molecular Advances in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease.International journal of molecular sciences · 2023Review
- Genetic investigation of Nordic patients with complement-mediated kidney diseases.Frontiers in immunology · 2023Article
- Full characterization of the three pathways of the complement system in patients with systemic lupus erythematosus.Frontiers in immunology · 2023Article
- Bioinformatics analysis of microarray data to identify hub genes, as diagnostic biomarker of HELLP syndrome: System biology approach.The journal of obstetrics and gynaecology research · 2022Article
- The yin and the yang of early classical pathway complement disorders.Clinical and experimental immunology · 2022Review
- Complement dysregulation is associated with severe COVID-19 illness.Haematologica · 2022Article
- A review of the alternative pathway of complement and its relation to HELLP syndrome: is it time to consider HELLP syndrome a disease of the alternative pathway.The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians · 2022Review
- Molecular Advances in Preeclampsia and HELLP Syndrome.International journal of molecular sciences · 2022Review
- Membrane cofactor protein (MCP; CD46): deficiency states and pathogen connections.Current opinion in immunology · 2021Review
- Thrombotic microangiopathy in aHUS and beyond: clinical clues from complement genetics.Nature reviews. Nephrology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundHELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome is a severe variant of hypertensive disorders of pregnancy affecting approximately 1% of all pregnancies, and has significant maternal and fetal morbidity. Previously, we showed that upregulation of the alternative pathway of complement (APC) plays a role in HELLP syndrome. We hypothesize that HELLP syndrome follows a 2-hit disease model similar to atypical hemolytic uremic syndrome (aHUS), requiring both genetic susceptibility and an environmental risk factor. Our objective was to perform a comparative analysis of the frequency of APC activation and germline mutations in affected women and to create a predictive model for identifying HELLP syndrome.
methodsPregnant women with HELLP syndrome, and healthy controls after 23 weeks of gestation were recruited, along with aHUS and thrombotic thrombocytopenic purpura participants. We performed a functional assay, the mHam, and targeted genetic sequencing in all groups.
resultsSignificantly more participants with rare germline mutations in APC genes were present in the HELLP cohort compared with controls (46% versus 8%, P = 0.01). In addition, significantly more HELLP participants were positive for the mHam when compared with controls (62% versus 16%, P = 0.009). Testing positive for both a germline mutation and the mHam was highly predictive for the diagnosis of HELLP syndrome.
conclusionHELLP syndrome is characterized by both activation of the APC and frequent germline mutations in APC genes. Similar to aHUS, treatment via complement inhibition to mitigate maternal and fetal morbidity and mortality may be possible.
fundingNational Heart Lung and Blood Institute grants T32HL007525 and R01HL133113.
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