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Alternative Complement Pathway Activation in the Severe Hypertensive Disorders of Pregnancy

1National Cerebral and Cardiovascular Center, Division of Counseling for Medical Genetics, Suita, Japan, 2National Cerebral and Cardiovascular Center, Department of Obstetrics and Gynecology, Suita, Japan, 3National Cerebral and Cardiovascular Center, Department of Cerebrovascular Medicine, Suita, Japan, 4Rakuno Gakuen University, Department of Clinical Nutrition, Ebetsu, Japan, 5Wakayama Medical University, Department of Molecular Genetics, Wakayama, Japan, 6National Cerebral and Cardiovascular Center, Department of Molecular Pathogenesis, Suita, Japan, 7Rakuno Gakuen University, Department of Medicine and Physiology, Ebetsu, Japan

Abstract Number: PB2532

Meeting: ISTH 2020 Congress

Theme: Women Health » Pregnancy and Pregnancy Complications

Background: Preeclampsia (PE) accompanied by proteinuria and/or other organ failures is categorized as one of hypertensive disorders of pregnancy (HDP). Recently, mutations of complement-related genes that predispose atypical hemolytic uremic syndrome (aHUS) have been reported in PE. This finding suggests that complement dysregulation should be involved in the pathogenesis of PE.

Aims: This study was conducted to investigate the relationship between HDP and abnormality of complement System.

Methods: We enrolled 4 normal pregnant individuals with a history of HDP and 10 HDP patients including 3 cases with gestational hypertension (GH) (severe:1, non-severe:2), 7 cases with PE (severe:5, non-severe:2). We measured plasma levels of complement-related factors (C3, C4, CH50, sC5b-9, Ba, C5a, CFH, anti-CFH antibody). In biochemical analyses, we classified plasma samples based on the symptoms, the severity, and the time of sampling (during pregnancy, early postpartum [within 3 days after delivery], and late postpartum [over 4 days after delivery]). We compared the plasma levels among the groups and non-pregnant healthy volunteers using mixed effect model. Genetic analysis of complement-related genes has been performed.

Results: Two severe HDP patients showed continuously elevated values of anti-CFH antibody, suggesting alternative pathway activation. None had rare variations in known aHUS predisposing genes. Pregnant individuals consecutively had higher levels of sC5b-9 before and after partum. Patients with severe HDP tended to have higher levels of Ba (an activation marker of alternative pathway). Patients with PE and severe HDP showed high Ba levels in the early postpartum period. Patients with PE had lower levels of C4 and CH50 before and after delivery. All pregnant individuals showed increased levels of C3, C4 and CH50 in the late postpartum period.

Conclusions: The activation of alternative pathway should be involved in the severity of HDP. Pregnancy-related thrombotic microangiopathy may be mainly induced in the late postpartum.

To cite this abstract in AMA style:

Neki R, Miyata T, Ohtani K, Hidaka Y, Ida K, Yokouchi-Konishi T, Nakanishi A, Yoshimatsu J, Kokame K, Wakamiya N, Inoue N. Alternative Complement Pathway Activation in the Severe Hypertensive Disorders of Pregnancy [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/alternative-complement-pathway-activation-in-the-severe-hypertensive-disorders-of-pregnancy/. Accessed March 3, 2021.

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