title: Distinct genetic and infectious profiles in Japanese neuromyelitis optica patients according to anti-aquaporin 4 antibody status.
abstract: OBJECTIVE
  To clarify whether genetic and common infectious backgrounds are distinct, according to anti-aquaporin 4 (AQP4) antibody status in Japanese patients with neuromyelitis optica (NMO).
  
  
  METHODS
  We analysed human leucocyte antigen (HLA)-DRB1 and HLA-DPB1 alleles, and IgG antibodies against Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus and Epstein-Barr virus nuclear antigen (EBNA) in 116 patients with NMO, including 39 patients with neuromyelitis optica spectrum disorder (NMOSD), 145 multiple sclerosis (MS) patients and 367 unrelated healthy controls. 77 NMO/NMOSD patients were seropositive for AQP4 antibody while 39 were seronegative.
  
  
  RESULTS
  Compared with healthy controls, NMO/NMOSD patients showed a significantly lower frequency of DRB1*0901 and significantly higher frequencies of DRB1*1602 and DPB1*0501, which conferred susceptibility to anti-AQP4 antibody positive NMO/NMOSD, but not antibody negative NMO/NMOSD. DRB1*0901 was a common protective allele, irrespective of the presence or absence of anti-AQP4 antibody. Anti-H pylori and anti-C pneumoniae antibodies were more commonly detected in anti-AQP4 antibody positive NMO/NMOSD patients than healthy controls. Antibody negative NMO/NMOSD patients did not differ from healthy controls regarding the presence of these antibodies. The presence or absence of antibodies against varicella zoster virus and EBNA did not vary among the groups. The frequencies of antibodies against these four pathogens were not significantly different between MS patients and healthy controls.
  
  
  CONCLUSIONS
  Our results suggest that HLA-DRB1*1602 and DPB1*0501 alleles and H pylori and Chlamydia pneumonia infection are risk factors only for anti-AQP4 antibody positive NMO/NMOSD but not for anti-AQP4 antibody negative NMO/NMOSD.
authors.affiliation: Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Noriko
authors.initials: N
authors.lastname: Isobe
authors.forename: Takuya
authors.initials: T
authors.lastname: Matsushita
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yonekawa
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Masaki
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawano
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Kira
mesh_terms: D000328:Adult; D000483:Alleles; D000907:Antibodies, Bacterial / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D051401:Aquaporin 4 / Q000276:immunology*; D001323:Autoantibodies / Q000235:genetics*; D016022:Case-Control Studies; D016993:Chlamydophila pneumoniae / Q000276:immunology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000378:metabolism; D005260:Female; D059868:HLA-DP beta-Chains; D059811:HLA-DRB1 Chains / Q000235:genetics*; D016480:Helicobacter pylori / Q000276:immunology; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000235:genetics / Q000378:metabolism; D009471:Neuromyelitis Optica / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*
chemical_list: C496030:AQP4 protein, human; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D051401:Aquaporin 4; D001323:Autoantibodies; D019309:Epstein-Barr Virus Nuclear Antigens; D059868:HLA-DP beta-Chains; C071170:HLA-DPB1 antigen; D059811:HLA-DRB1 Chains