AT1AA (Angiotensin II Type-1 Receptor Autoantibodies): Cause or Consequence of Human Primary Aldosteronism?

AT1AA (Angiotensin II type-1 receptor autoantibodies) were first detected in patients with primary aldosteronism (PA) because of aldosterone-producing adenoma (APA) with an in-house developed assay, but it remained unclear if they can be ascertained also with commercially available assays and if they have a functional role. Aims of our study were to investigate if (1) commercially available kits allow detection of raised AT1AA titer in APA; (2) this titer is normalized by adrenalectomy; and (3) AT1AA display any biological roles in vitro. We measured with 2 ELISA kits the AT1AA titer in serum of APA patients and its changes after adrenalectomy. We also investigated AT1AA bioactivity by using AT1-R (angiotensin type-1 receptor)-transfected Chinese hamster ovary and human adrenocortical carcinoma cells, and by measuring aldosterone synthase (CYP11B2) expression in human adrenocortical carcinoma cells after incubation with IgG. Both kits allowed detection of higher AT1AA levels in APA patients than in healthy subjects; surgical cure of PA did not decrease this titer at 1-month follow-up. Human adrenocortical carcinoma cells stimulation with IgG purified from sera of APA patients increased both CYP11B2 expression and aldosterone release (+40% and +76%, respectively, versus healthy subjects). However, no detectable effect of IgG was seen in Chinese hamster ovary cells expressing AT1-R. These findings support the contentions that (1) the raised AT1AA titer does not seem to be a consequence of hyperaldosteronism as it did not normalize after its cure; (2) AT1AA act as weak stimulators of aldosterone biosynthesis, but this effect can be identified only by using a sensitive in vitro technique.