Key result
Connective tissue disease patients with constrictive vasculopathies had significantly higher mean ELISA scores for anti-ACE2 autoantibodies compared to patients without vasculopathies (P < 0.0005), with 94% of vasculopathy patients testing above baseline.
Case-Control (n=70)
No
p-value: p=<0.0005
Autoantibodies to ACE2 are elevated in patients with connective tissue diseases and constrictive vasculopathies, and these antibodies functionally inhibit ACE2 activity.
Anti-ACE2 autoantibodies associate with constrictive vasculopathies in CTD; hypothesis-generating and requires prospective validation before any clinical role.
INTRODUCTION: Angiotensin-converting enzyme (ACE) 2, a homolog of ACE, converts angiotensin (Ang) II into Ang(1-7), and the vasoprotective effects of Ang(1-7) have been documented. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with connective tissue diseases to constrictive vasculopathy, pulmonary arterial hypertension (PAH), or persistent digital ischemia. METHODS: Serum was examined from 42 patients with systemic lupus erythematosus (SLE), scleroderma, or mixed connective tissue disease. Eighteen vasculopathy patients with PAH (five cases) and/or persistent digital ischemia (16 cases) were compared with 24 patients without these vasculopathies (control patients) for serum reactivity to purified recombinant human ACE2, using an ELISA. RESULTS: The sera from 17 of the 18 (94%) vasculopathy patients had ELISA scores above the baseline level determined using control sera from 28 healthy subjects, and the mean ELISA score in the vasculopathy patients was significantly higher than that in the control patients (P<0.0005). The relative activity of serum ACE2, which was defined using a reference serum, correlated inversely with the ELISA scores for serum anti-ACE2 antibodies in the 18 vasculopathy patients (R2=0.6872). The IgG fraction from vasculopathy patients, but not from healthy subjects, inhibited ACE2 activities in vitro. Consistent with this, immunosuppressive therapy given to one SLE patient with digital necrosis markedly decreased the anti-ACE2 antibody titer and restored serum ACE2 activity. CONCLUSIONS: Autoantibodies to ACE2 may be associated with constrictive vasculopathies.
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Takahashi et al. (2010) conducted a case-control in Connective tissue diseases with constrictive vasculopathies (n=70). Constrictive vasculopathies (PAH or persistent digital ischemia) vs. Connective tissue disease without vasculopathies was evaluated on Serum reactivity to purified recombinant human ACE2 (ELISA scores) (p=<0.0005). Connective tissue disease patients with constrictive vasculopathies had significantly higher mean ELISA scores for anti-ACE2 autoantibodies compared to patients without vasculopathies (P < 0.0005), with 94% of vasculopathy patients testing above baseline.
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