The complex regulation of the MMP3 promoter may also explain the differences in reporter activity between pGL3-mutant and pGL3-G in HUVEC cells observed here and the opposite findings in others’research. Pre-eclampsia is a serious hypertensive disorder during pregnancy that affects 3%-5% of pregnancies, and remains the leading cause of maternal and neonatal mortalities and morbidities in the world. It is a multi-systemic disease with features such as hypertension and proteinuria. In serious cases, termination of pregnancy is the only available option to prevent further health deterioration of the fetus and mother. To date, the factors and mechanisms involved in the pathogenesis of pre-eclampsia remain poorly understood. To promote academic research and health care benefits from the GPRD Studies have described the role of autoantibodies against a1 adrenoreceptor in primary and malignant hypertension. Previously, we demonstrated that the presence of autoantibodies against b1, b2, and a1 adrenoreceptors, which bind to the second extracellular loop of the receptors, are highly prevalent in hypertensive heart disease and may participate in its pathogenesis. In recent years, evidence has accumulated that suggests that autoimmunity participates in the pathogenesis of pre-eclampsia. Recently, numerous studies have shown that pre-eclamptic women possess autoantibodies against angiotension II type 1 receptor, which bind to and activate the receptor, consequently provoking biological responses relevant to the pathogenesis of pre-eclampsia. The aim of this study was to investigate differences in the frequencies of anti-b1, b2, and a1-ARs among patients with severe pre-eclampsia, compared to normal pregnancy women and non-pregnant controls. The second aim was to investigate the relationship between the presence of anti-b1, b2, and a1-ARs and perinatal mortality and morbidity. We used synthetic peptides corresponding to amino acid sequences of the second extracellular loop of the human b1, b2, and a1 ARs, to test sera from patients with severe pre-eclampsia, normal pregnancy women, and non-pregnant controls. In this study, we demonstrated for the first time that positivity for anti-b1, b2, and a1-ARs was associated with severe preeclampsia. The frequencies and titers of anti-b1, b2, and a1-ARs were significantly higher in women with severe pre-eclamptic, when compared to normal pregnancy women and non-pregnant healthy controls. The presence of the three autoantibodies was associated with both adverse maternal and perinatal clinical outcomes including hypertension, pregnancy complications, fetal growth restriction, fetal distress, preterm birth, low birth weight, perinatal death, and long-term hospitalization of neonates. The pathogenesis of pre-eclampsia remains obscure, but is likely multifactorial involving abnormal placentation, reduced placental perfusion, endothelial cell dysfunction, and systemic vasospasm. An immune mechanism has long been postulated in the pathogenesis of pre-eclampsia. Immune maladaptation may impair invasion of spiral arteries by endovascular cytotrophoblast cells. Studies have suggested that repeated exposure to sperm from a particular male partner prior to pregnancy promotes immune tolerance and reduces the risk of defective trophoblast invasion. Autoantibodies, such as anticardiolipin and anti-b2glycoprotein-1 antibody, have been detected in pre-eclampsia patients. From the first report that described the presence of autoantibody against angiotensin II type 1 receptor in preeclampsia patients.