OC 25.5 - Endothelial damage and complement dysregulation in fetuses from mothers with preeclampsia

Sunday, June 25, 2023

15:45 – 16:00 ET

Room: 511

Session Available As: On-Demand

Presenting Author(s)

Alex Ramos López

Phd Student
Hemostasis and Erythropathology Unit, Centre Diagnòstic Biomèdic (CDB), Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain

Co-Author(s)

ly

lina youssef

Doctor
Josep Carreras Leukaemia Research Institute
barcelona, Catalonia, Spain
PM

Patricia Molina

Laboratory Technician
Hemostasis and Erythropathology Laboratory, Hematopathology, Pathology Department, Centre Diagnòstic Biomèdic (CDB), Hospital Clínic, Barcelona, Spain
Barcelona, Catalonia, Spain
Blanca De Moner Rafel, PhD Student (she/her/hers)

PhD student
Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona
Barcelona, Catalonia, Spain
Julia Martinez-Sanchez, PhD

PhD student
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
Ana Belén Moreno-Castaño, MD

Medical Doctor
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
GE

Gines Escolar

MD PhD Senior Consultant
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
EC

Enric Carreras

Medical Doctor
Josep Carreras Leukaemia Research Institute, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
EG

Eduard Gratacos

Doctor
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
barcelona, Catalonia, Spain
FC

Fatima Crispi

Doctor
BCNatal | Fetal Medicine Research Center (Hospital Clínic and Hospital Sant Joan de Déu), Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
MD

Maribel Diaz-Ricart

PhD Senior Consultant
Hemostasis and Erythropathology Laboratory, Hematopathology, Department of Pathology, Centre de Diagnòstic Biomèdic (CDB), Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain
MP

Marta Palomo

PhD
Hematology External Quality Assessment Laboratory, Biomedical Diagnostic Center, Hospital Clinic of Barcelona, Barcelona, Spain.
Barcelona, Catalonia, Spain

Background: Preeclampsia (PE) is a pathological pregnancy condition characterized by elevated blood pressure and proteinuria that can result in complications for both the mother and the fetus. Recent studies demonstrated that PE is associated with endothelial damage and complement dysregulation in mothers, however, there is no data regarding fetuses.

Aims: To evaluate endothelial damage and complement biomarkers, and the complement system function in fetuses from PE pregnancies.

Methods: Cord blood samples were obtained from PE (n=41) and normotensive (n=40) pregnancies. Plasma biomarkers were analyzed, including VCAM-1, TNFR1, VWF and sC5b-9. Complement activation was assessed by analyzing deposits of the complement membrane attack complex (C5b-9) on cultured endothelial cells (HMEC-1), by immunofluorescence, after exposing them to activated plasma (1:1 mix of patient’s citrated plasma and healthy subjects pooled sera). C5b-9 deposits were calculated as percentage of labeled area vs. the total area analyzed. Results were expressed as fold increase (mean±SEM) vs. those obtained with the plasma pool from healthy subjects.

Results: VCAM-1 and TNFR1 levels were significantly higher in PE fetal sera (549,0±15,7 ng/mL vs. 352,3±28,9 ng/mL; and 2989,1±289,2 pg/mL vs 1252,2±247,3 pg/mL respectively p< 0,05). Differences in soluble VWF were not significant between groups (22807,1±4144,2 ng/mL vs. 10435,8±1829,2 ng/mL). sC5b-9 was higher in PE fetal samples (873,7±110,4 ng/mL vs. 631,1±121,9 ng/mL) while C5b-9 deposits induced by PE fetal plasma were significantly lower than those induced by control fetus samples (0,09±0,02 vs. 0,60±0,17 p< 0,05).

Conclusion(s): High levels of the inflammation-related markers VCAM-1 and TNFR1 indicate endothelial damage in the fetuses of PE mothers compared to healthy fetuses , whereas no differences were observed regarding prothrombotic biomarkers. Regarding the complement system, the superior levels of sC5b9 in PE fetuses are in contrast with the reduction in complement function assays. More research is needed to clarify these data.

Learning Objectives:

identify the impact of preeclampsia in fetuses endothelial health and complement system
reproduce the assays to evaluate in vitro the endothelial state and complement dysregulation.
describe the most important characteristics of preeclampsia and its severe consequences and improve the manage of these patients in future