Angiotensin II Receptor Type 1 Autoantibodies in Patients with Primary Aldosteronism

Introduction: Primary aldosteronism (PA) is a common cause of hypertension and is characterized by renin-independent aldosterone secretion. Determination of PA subtype (i.e., unilateral vs. bilateral) is clinically important to inform treatment. Immune mechanisms may have a role in the pathogenesis of PA. The aims of this study were to investigate the prevalence of AT1 autoantibodies in patients with PA, to explore whether they are differentially associated with the two main subtypes, and to determine if the presence of autoantibodies varies according to disease duration. Methods: We conducted a cross-sectional study of patients with PA who were referred through the regional Endocrine Clinic in Calgary, Alberta, Canada for adrenal vein sampling (AVS) from April 2023 to July 2024. We also included healthy controls (n=50). Patients and healthy controls had AT1 autoantibody titres measured. AT1 autoantibodies were defined as positive when >17 U/mL and negative if ≤17 U/mL. AVS was used as a standard to determine PA subtype. For the analysis, we estimated the prevalence of AT1 autoantibodies in patients with PA who were referred for AVS. Using multivariable logistic regression, we determined whether AT1 autoantibodies were independently associated with the subtype of PA, after adjusting for other major clinical predictors. And, we examined for whether the presence of AT1 autoantibodies was independently associated with duration of disease. Results: 105 patients with PA (mean age, 53.1 years; 45.7% male), and 50 healthy controls (mean age, 47.4 years; 50.0% male) were included. Positive AT1 autoantibodies were present in 23.0% (24) of patients with PA compared to 10.0% (5) of people who were healthy, and this difference bordered on statistical significance (p=0.055). Ninety-nine patients with successful AVS were included to examine if the AT1 autoantibodies predict the subtype of PA. Higher AT1 autoantibody levels were independently associated with lateralization, indicating unilateral PA (OR, 1.05; 95% CI, 1.00-1.11; p=0.047), after adjusting for other major clinical predictors. No correlation was found between AT1 autoantibodies and duration of disease. Discussion: In this study AT1 autoantibodies were found to be present in 23% of people with PA compared to 10% in the general population. AT1 autoantibodies were also found to be associated with lateralizing disease, but not disease duration. Overall, AT1 autoantibodies are common in patients with PA and may be helpful for stratifying patients according to PA subtype.