Background/Purpose: We previously reported that inhibitory autoantibodies to angiotensin converting enzyme 2 (ACE2) predisposed individuals to connective tissue diseases (i.e., scleroderma or systemic lupus erythematosus [SLE]) and constrictive vasculopathies. That study included SLE patients with digital ulcer, scleroderma patients with pulmonary arterial hypertension (PAH), and control patients with remitted SLE without vasculopathy. Preliminary data in our further experiment suggested that patients with active SLE without vasculopathy also had high titers of serum anti-ACE2 antibodies. This study investigated the presence of anti-ACE 2 antibodies in patients with SLE and evaluated the effects of these antibodies on ACE2 activity.

Methods: Serum samples were obtained for this study from 35 non-vasculopathy patients with active SLE, three vasculopathy patients with both SLE and PAH, and 44 control patients with rheumatoid arthritis (RA). The sera were assessed for anti-ACE2 antibodies by enzyme-linked immunosorbent assay (ELISA) using purified recombinant human ACE2. Twenty-six non-vasculopathy patients with remitted SLE, 21 of whom were described in our previous study, were also (re)examined by ACE2 ELISA as a control. ELISA score above the baseline level, which was determined using sera from 28 healthy subjects, were classified as positive for anti-ACE2 antibodies. IgG fractions were prepared, using protein G sepharose beads, from the sera of subjects with high ACE2 ELISA scores and were used to evaluate inhibition of ACE2 activity in vitro.

Results: All three PAH patients with SLE were positive for anti-ACE2 antibodies (mean optical density [OD], 0.63±0.32). Of the 35 non-vasculopathy patients, 32 (91%) with active SLE were positive for anti-ACE2 antibodies (mean OD, 0.78 ±0.42), and the mean ELISA score was significantly higher than that of remitted SLE patients (mean OD, 0.18 ±0.15; p < 0.00000001) or RA patients (mean OD, 0.06 ±0.05 ;  p < 0.0000000001). Using serum IgG fractions from SLE patients with high ACE2 ELISA titers, statistically significant suppression of ACE2 activity in vitro was found for 1/15 non-vasculopathy patients, 3/3 PAH patients (p = 0.0049), and 7/7 vasculopathy (PAH or digital ulcer) patients (p= 0.000047), including four who were described in our previous study.

Conclusion: Most patients with active SLE or vasculopathy were positive for serum anti-ACE2 antibodies, and inhibitory antibodies were associated with vasculopathy, but not with active SLE.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-of-inhibitory-or-non-inhibitory-autoantibodies-to-angiotensin-converting-enzyme-2-ace2-in-patients-with-systemic-lupus-erythematosus/