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Published on: January 26, 2024
Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in
Theodora-Maria Venou1, Evangelia Vetsiou1, Christos Varelas2
1Hematological Laboratory, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece.
Insights
Preeclampsia and HELLP syndrome involve decreased ADAMTS13 activity and increased complement activation. Genetic variants in regulatory genes were also identified, suggesting potential new biomarkers for these pregnancy complications.
Area of Science:
- Reproductive Medicine
- Hematology
- Immunology
Background:
- Preeclampsia is a severe pregnancy disorder with potential complications like HELLP syndrome.
- The roles of ADAMTS13, von Willebrand factor, and the complement system in preeclampsia pathogenesis are not fully understood.
Purpose of the Study:
- To investigate the involvement of ADAMTS13, von Willebrand factor, and the complement system in preeclampsia and HELLP syndrome.
- To identify potential genetic risk factors and biomarkers for these conditions.
Main Methods:
- Genetic sequencing of ADAMTS13 and complement regulatory genes in 30 preeclamptic patients and 15 controls.
- Assays for complement activation (modified Ham test), ADAMTS13 activity, von Willebrand antigen (vWFAg), and soluble C5b-9 levels.
Main Results:
- Preeclamptic patients exhibited reduced ADAMTS13 activity and elevated C5b-9 levels.
- vWFAg levels significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003).
- Risk-factor variants were identified in ADAMTS13 and several complement regulatory genes (C3, thrombomodulin, CFB, CFH, MBL2, MASP2).
Conclusions:
- Decreased ADAMTS13 activity, elevated complement activation, and specific genetic variants are associated with preeclampsia/HELLP syndrome.
- These findings suggest that ADAMTS13, complement system components, and related genetic factors may play a role in disease pathogenesis.
- Further research is warranted to explore their potential as diagnostic or prognostic biomarkers.
Abstract:
Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.
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