CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity

T. Matsushita, N. Isobe, M. Kawajiri, M. Mogi, K. Tsukuda, M. Horiuchi, Y. Ohyagi, J. Kira

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Abstract

Background: Anti-aquaporin-4 (AQP4) antibody targets perivascular astrocyte foot processes, which contain abundant angiotensinogen, a precursor of angiotensin II, angiotensin-converting enzyme (ACE) and ACE2. Objective: To disclose any abnormality in the intrathecal angiotensin II metabolic pathway in Japanese patients with neuromyelitis optica (NMO) or NMO spectrum disorders (NMOs) and positive for anti-AQP4 antibody. Methods: We measured CSF angiotensin II, ACE and ACE2 levels in 15 anti-AQP4 antibody-positive patients with NMO or NMOs, 21 anti-AQP4 antibody-negative multiple sclerosis (MS) patients, 32 patients with other neurological diseases (OND) and 24 non-neurologic controls, using established ELISAs. Results: CSF angiotensin II levels were lower in patients with NMO/NMOs (2.01 ± 1.82 pg/ml) and those with MS (3.15 ± 1.67 pg/ml) than in the OND (5.41 ± 2.34 pg/ml) and control groups (6.71 ± 2.65 pg/ml) (Pcorr < 0.005). The difference in CSF angiotensin II levels between NMO/NMOs and MS patients was nearly significant (Puncorr = 0.052). In NMO/NMOs and MS patients, angiotensin II levels were negatively correlated with CSF/serum albumin ratio (P < 0.05). ACE levels in CSF were lower in patients with NMO/NMOs (34.3 ± 5.61 ng/ml) than in MS patients (42.5 ± 8.19 ng/ml, Pcorr = 0.035) and controls (44.7 ± 4.02 ng/ml, Pcorr < 0.0003) while ACE2 levels were lower in NMO/NMOs (1.13 ± 0.49 ng/ml) and MS (1.75 ± 0.86 ng/ml) patients than in controls (2.76 ± 0.23 ng/ml, Pcorr < 0.001 for both). Conclusion: CSF angiotensin II, ACE, and ACE2 levels are decreased in NMO/NMOs patients with anti-AQP4 antibody, reflecting severe destruction of perivascular astrocytes.

Original languageEnglish
Pages (from-to)41-45
Number of pages5
JournalJournal of the Neurological Sciences
Volume295
Issue number1-2
DOIs
Publication statusPublished - Aug 15 2010

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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