Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
Autoantibodies to Angiotensin Converting Enzyme 2 in Patients with Rheumatic Diseases
Takahashi, Yuko, Haga, Shiori, Yamashita, Hiroyuki, Ishizaka, Yukihito, Mimori, Akio
Angiotensin-converting enzyme 2 (ACE2), a homologue of ACE, degrades angiotensin (Ang) II to Ang-(17). Recent studies have indicated that ACE2 plays a vasoprotective role in cardiovascular pathophysiology. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with rheumatic diseases to vasculopathies.
Serum samples were obtained from 30 patients with systemic lupus erythematosus (SLE), scleroderma, or mixed connective tissue disease, and 30 normal control subjects. Of these, 9 patients had vasculopathies including pulmonary arterial hypertension (PAH) (n=4), progressive digital ischemia (n=2), or cutaneous vasculitis (n=3). The sera were assessed for anti-ACE2 antibodies by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human ACE2.
Serum anti-ACE2 antibodies were detected in all of the 9 patients with vasculopathies and were negative in the remaining patients and healthy subjects. A patient with active SLE and ischemic digital gangrene (case 1) and a scleroderma patient with lethal PAH of rapid progression (case 2) showed extremely high serum levels of anti-ACE2 antibodies. The sera of case 1 and case 2 showed a deficient peptidase activity of ACE2. Digital ischemia in case 1 resolved after combination therapy with a steroid, vasodilating drugs, and plasmapheresis. The serum tests in case 1 after therapy showed that the ELISA score of anti-ACE2 antibodies was markedly reduced (p<0.05) and ACE2 activity had recovered significantly (p<0.05) compared to those before therapy. The serum ACE2 protein levels assessed by immunoblotting were similar between before and after therapy for case 1. These results suggested that anti-ACE2 antibodies inhibited enzymatic activity of ACE2.
Serum autoantibodies to ACE2 may be associated with vasculopathies in patients with rheumatic diseases.
To cite this abstract, please use the following information:
Takahashi, Yuko, Haga, Shiori, Yamashita, Hiroyuki, Ishizaka, Yukihito, Mimori, Akio; Autoantibodies to Angiotensin Converting Enzyme 2 in Patients with Rheumatic Diseases [abstract]. Arthritis Rheum 2009;60 Suppl 10 :115