Anti-angiotensin 2 receptor 1 antibody (anti-AT1R) and anti-endothelin receptor type a (anti-ETAR) as biomarkers of endothelial dysfunction in systemic sclerosis (SSc) patients

Background: Aims of this study were to evaluate the serum level of autoantibodies against G-protein-coupled receptors for Angiotensin II type 1 (anti-AT1R) and endothelin receptor type A (anti-ETAR) in systemic sclerosis (SSc) patients and healthy controls (HC) and to evaluate the associations of these antibodies with microvascular complication of SSc, such as digital ulcers (DUs), subclinical renal vasculopathy and early pulmonary vasculopathy. Research design and methods: Sixty-four SSc patients and 20 HC were tested for anti-AT1R and anti-ETAR. Results: SSc patients had higher anti-AT1R [7.78 ng/ml (IQR 6.14;12.16) vs 3.25 ng/ml (IQR 2.60;4.70), p < 0.001] and anti-ETAR [0.16 OD (IQR 0.14;0.17) vs 0.10 OD (IQR 0.10;0.12), p < 0.001] than HC. SSc patients with DUs had higher anti-AT1R [10.79 ng/ml (IQR 7.32;14.15) vs 6.76 ng/ml (IQR 5.88;7.88), p < 0.001] and anti-ETAR [0.16 OD (IQR 0.15;0.18) vs 0.15 OD (IQR 0.13;0.16), p < 0.01] than SSc patients without DUs. We found a positive correlation between renal resistive index (RRI) and anti-AT1R (r = 0.357, p < 0.01) or anti-ETAR (r = 0.442, p < 0.001) and a negative correlation between tricuspid annular plane systolic excursion/pulmonary arterial systolic pressure (TAPSE/sPAP) and anti-AT1R (r = −0.436, p < 0.001) or anti-ETAR (r = −0.334, p < 0.01). Conclusions: Anti-AT1R and anti-ETAR may play a pathogenic role in endothelial dysfunction.