Th e present fi ndings by Takahashi and colleagues reveal increased expression of circulating ACE2 in patients with vasculopathy utilizing a novel protein capture assay [1] . Despite the increased levels of the enzyme, ACE2 activity was markedly lower in comparison with the control group. Indeed, the authors report the presence of circulating levels of ACE2 antibodies that exhibit inhibitory activity in vitro. Previous studies showed that commercial sources of antibodies against ACE2 also inhibit enzyme activity, suggesting the epitope may encompass the catalytic site [4] ; however, the present study is the fi rst to identify autoantibodies that attenuate enzyme activity in a patient population.