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Arthritis Res Ther. 2010; 12(3): R85.
Published online May 14, 2010. doi:  10.1186/ar3012
PMCID: PMC2911869
Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases
Yuko Takahashi,#1 Shiori Haga,#2 Yukihito Ishizaka,2 and Akio Mimoricorresponding author1
1Division of Rheumatic Diseases, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
2Department of Intractable Diseases, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan
corresponding authorCorresponding author.
#Contributed equally.
Yuko Takahashi: ytakahas/at/hosp.ncgm.go.jp; Shiori Haga: shihaga/at/ri.imcj.go.jp; Yukihito Ishizaka: zakay/at/ri.imcj.go.jp; Akio Mimori: amimori/at/hosp.ncgm.go.jp
Received December 12, 2009; Revised March 12, 2010; Accepted May 14, 2010.
Abstract
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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