Autoimmune Antibodies in Orthostatic Intolerance Syndromes

Orthostatic intolerance (OI) is defined as the development of characteristic symptoms while standing, which significantly improve by recumbency. The most common forms are vasovagal syncope (VVS), orthostatic hypotension, and postural orthostatic tachycardia syndrome (POTS). Lately, there has been a growing body of evidence that autoimmunity may play a role in the pathophysiology of orthostatic intolerance syndromes. The aim was to compare the presence and levels of autoimmune autoantibodies in patients with POTS, VVS syncope, and the control group. Altogether, 61 patients with symptoms of orthostatic intolerance were evaluated in this study - 19 POTS patients and 42 VVS patients. The control group contained 22 patients with no signs of orthostatic intolerance. We evaluated levels of autoantibodies against three subtypes of G-protein coupled adrenergic receptor (alpha-1 and beta-1,2 adrenergic receptors), type 4 of muscarinic acetylcholine receptor, and angiotensin II type 1 receptor. We compared the levels between the three patient groups. Significantly higher levels of angiotensin II type 1 receptor (AT1R) autoantibodies were found in the POTS group compared with controls (0.67± 0.35 ng/ml vs. 0.38±0.32 ng/ml, p=0.008). There was no significant difference in AT1R antibodies between the VVS and control groups (0.46±0.34 ng/ml vs 0.38±0.32 ng/ml, p= 0.38). Autoantibody concentration against ADRA1, ADRB1, ADRB2, and M4R were not significantly different between the groups. Autoimmune mechanisms may lead to abnormal regulation of the renin-angiotensin-aldosterone system and may contribute to the pathophysiology of POTS.