Introduction: Systemic sclerosis (SSc) is an autoimmune disease caused by the imbalance between the activity of angiotensin II and angiotensin-(1-7). Their balance should be controlled by angiotensin-converting enzyme 2 (ACE2), which degrades angiotensin II into angiotensin-(1-7). Previously, autoantibodies to ACE2 (anti-ACE2) were identified in patients with vasculopathy due to different connective tissue diseases, including SSc, but their frequency in SSc was not further analyzed. The aim of the research was to investigate the prevalence and potential role of those anti-ACE2 antibodies in SSc patients.
Materials and methods: There were enrolled 27 patients with SSc and 23 healthy donors. ELISA assay determined the presence of anti-ACE2 autoantibodies in serum samples. The results were compared to plasma measurements of angiotensin-(1-7) level via commercial ELISA.
Results: The presence of anti-ACE2 autoantibodies was confirmed in five patients with SSc and two healthy controls. Two of those SSc subjects were anti-Scl70+, another two were double anti-Scl70+ and anti-Ro/SSA+, and anti-PM/Scl antibodies were detected in one patient. Median plasma level of Ang-(1-7) in anti-ACE2 negative patients was 47.4 pg/ml and stayed below the detection level in anti-ACE2 positive subjects. The plasma level of Ang-(1-7) was undetectable in four SSc patients, and three of them were anti-ACE2 positive.
Conclusions: Anti-ACE2 antibodies appear to be other functional autoantibodies with the potential to dysregulate the balance between Ang II and Ang-(1-7). They are non-specific for SSc and probably result from polyautoimmunity which affect some of SSc patients. Their occurrence in SSc settings may be associated with a severe depletion of plasma Ang-(1-7).
Keywords: Functional autoantibodies; angiotensin; angiotensin converting enzyme 2; microvasculopathy; systemic sclerosis.