Diagnosing and Treating Hypertensive Disorders of Pregnancy?
The Answer May Now Be Less BAFF-ling
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See related article, pp 1007–1013
Hypertensive disorders of pregnancy (HDP), which include gestational hypertension, preeclampsia, hemolysis, elevated liver enzymes, and low platelets, are leading causes of maternal and perinatal morbidity and mortality.1 Treatment of HDP is complicated by our relatively poor understanding of the pathophysiological processes that give rise to the conditions and by the fact that several first-line antihypertensive agents, including angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, are contraindicated during pregnancy.1 Hence, improved clinical management of HDP in the future will rely on a better understanding of disease mechanisms and identification of new targets for early diagnosis and therapeutic intervention.
Research over several decades has highlighted a potential role for dysregulation of the humoral immune system as a cause of the elevated blood pressure and end-organ damage associated with both HDP and chronic (essential) hypertension. Specifically, there is substantial clinical and preclinical evidence for B-cell activation and elevated levels of IgG and IgM autoantibodies in the blood and tissues during hypertension.2 These autoantibodies have been shown to have agonistic effects on key receptors and ion channels involved in the regulation of vascular tone, cardiac contractility, and renal function,2 suggestive of a mechanistic link between the humoral immune system and the development of high blood pressure, and highlighting B-cell activation as a potential target for future therapies.
BAFF (B-cell activating factor) is a homotrimeric cytokine belonging to the TNF (tumor necrosis factor) superfamily.3 It is produced by monocytes, macrophages, and dendritic cells and acts as the natural ligand for 3 receptors—the BAFF-R (BAFF …