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

Purpose:

Angiotensin-converting enzyme 2 (ACE2), a homologue of ACE, degrades angiotensin (Ang) II to Ang-(1–7). 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.

Methods:

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.

Results:

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.

Conclusion:

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
DOI: 10.1002/art.25198

Abstract Supplement

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