Hypertensive disorders are life-threatening diseases with high morbidity and mortality, affecting billions of individuals worldwide. A multitude of underlying conditions may contribute to
hypertension, thus the need for a plethora of treatment options to identify the approach that best meets the needs of individual patients. A growing body of evidence indicates that (1)
autoantibodies that bind to and activate the major
angiotensin II type I (AT₁) receptor exist in the circulation of patients with hypertensive disorders, (2) these
autoantibodies contribute to disease pathophysiology, (3) antibody titers correlate to the severity of the disease, and (4) efforts to block or remove these pathogenic
autoantibodies have therapeutic potential. These
autoantibodies, termed AT₁ agonistic
autoantibodies have been extensively characterized in
preeclampsia, a life-threatening hypertensive condition of pregnancy. As reviewed here, these
autoantibodies cause symptoms of
preeclampsia when injected into pregnant mice. Somewhat surprisingly, these auto
antibodies also appear in 3 animal models of
preeclampsia. However, the occurrence of AT₁ agonistic
autoantibodies is not restricted to pregnancy. These
autoantibodies are prevalent among kidney transplant recipients who develop severe transplant rejection and
malignant hypertension during the first week after
transplantation. AT₁ agonistic
autoantibodies are also highly abundant among a group of patients with
essential hypertension that are refractory to standard
therapy. More recently these
autoantibodies have been seen in patients with the
autoimmune disease,
systemic sclerosis. These 3 examples extend the clinical impact of AT₁ agonistic
autoantibodies beyond pregnancy. Research reviewed here raises the intriguing possibility that
preeclampsia and other hypertensive conditions are
autoimmune diseases characterized by the presence of pathogenic
autoantibodies that activate the major
angiotensin receptor, AT₁. These pathogenic
autoantibodies could serve as presymptomatic
biomarkers and therapeutic targets, thereby providing improved medical management for these conditions.