title: CSF angiotensin II and angiotensin-converting enzyme levels in anti-aquaporin-4 autoimmunity.
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) (P(corr)<0.005). The difference in CSF angiotensin II levels between NMO/NMOs and MS patients was nearly significant (P(uncorr)=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, P(corr)=0.035) and controls (44.7+/-4.02 ng/ml, P(corr)<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, P(corr)<0.001 for both).
  
  
  CONCLUSIONS
  CSF angiotensin II, ACE, and ACE2 levels are decreased in NMO/NMOs patients with anti-AQP4 antibody, reflecting severe destruction of perivascular astrocytes.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: N
authors.initials: N
authors.lastname: Isobe
authors.forename: M
authors.initials: M
authors.lastname: Kawajiri
authors.forename: M
authors.initials: M
authors.lastname: Mogi
authors.forename: K
authors.initials: K
authors.lastname: Tsukuda
authors.forename: M
authors.initials: M
authors.lastname: Horiuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Ohyagi
authors.forename: J
authors.initials: J
authors.lastname: Kira
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000134:cerebrospinal fluid*; D051401:Aquaporin 4 / Q000276:immunology*; D015551:Autoimmunity / Q000502:physiology*; D002461:Cell Line, Transformed; D020278:Demyelinating Autoimmune Diseases, CNS / Q000134:cerebrospinal fluid* / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000134:cerebrospinal fluid*; D012189:Retrospective Studies; D013223:Statistics as Topic; D014162:Transfection / Q000379:methods
chemical_list: D051401:Aquaporin 4; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D007703:Peptidyl-Dipeptidase A