title: Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel.
abstract: BACKGROUND
  Previous studies have revealed different human leukocyte antigen (HLA) associations in multiple sclerosis (MS) and neuromyelitis optica (NMO), further discriminating these two demyelinating pathological conditions. In worldwide analyses, NMO and opticospinal MS are represented at higher proportions among demyelinating conditions in African, East-Asian and Latin American populations. There are currently no data regarding the prevalence of NMO in Middle East Muslims. The population in Israel is diverse in many ways, and includes subpopulations, based on religion and ethnicity; some exhibit genetic homogeneity. In Israel, the incidence of MS is lower in the Muslim population than the Jewish population and Muslims carry different allele frequency distribution of HLA haplotypes.
  
  
  OBJECTIVE
  To evaluate the occurrence of anti-AQP4 seropositivity in the Israeli Muslim population among patients with central nervous system (CNS) demyelinating conditions; and to identify the HLA DR and DQ profiles of Muslim Arab Israeli patients with NMO spectrum of diseases (NMOSD).
  
  
  METHODS
  The prevalence of anti-AQP4 seropositivity was analyzed in 342 samples, obtained from patients with various CNS demyelinating conditions and in a validation set of 310 samples. HLA class II alleles (HLA-DRB1 and DQB1) were examined in DNA samples from 35 Israeli Muslim Arabs NMO patients and compared to available data from 74 Israeli Muslim controls.
  
  
  RESULTS
  Our data reveal a significantly increased prevalence of anti-AQP4 seropositivity, indicative of NMOSD, in Muslim Arab Israeli patients with initial diagnosis of a CNS demyelinating syndrome. In this population, there was a positive association with the HLA-DRB1*04:04 and HLA-DRB1*10:01 alleles (p=0.03), and a strong negative association with the HLA-DRB1*07 and HLA-DQB1*02:02 alleles (p=0.003, p=0.002).
  
  
  CONCLUSIONS
  Our findings indicate a possibly increased prevalence of NMOSD in Muslim Arabs in Israel with distinct (positive and negative) HLA associations. Further studies in patients with similar genetic backgrounds worldwide could help to confirm our findings and identify more genetic susceptibility factors for NMO, contributing to our general understanding of the pathogenesis of NMOSD.
authors.affiliation: Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Medical Center, Hebrew University of Jerusalem, The faculty of Medicine, Israel.
authors.forename: Livnat
authors.initials: L
authors.lastname: Brill
authors.affiliation: Department of Statistics, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel.
authors.forename: Micha
authors.initials: M
authors.lastname: Mandel
authors.affiliation: Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Medical Center, Hebrew University of Jerusalem, The faculty of Medicine, Israel.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Karussis
authors.affiliation: Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Medical Center, Hebrew University of Jerusalem, The faculty of Medicine, Israel.
authors.forename: Panayiota
authors.initials: P
authors.lastname: Petrou
authors.affiliation: Tissue Typing Laboratory, Hadassah Medical Center, Ein Karem, Jerusalem, 91120, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Miller
authors.affiliation: Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Medical Center, Hebrew University of Jerusalem, The faculty of Medicine, Israel.
authors.forename: Tamir
authors.initials: T
authors.lastname: Ben-Hur
authors.affiliation: Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Arnon
authors.initials: A
authors.lastname: Karni
authors.affiliation: Department of Hematology, Braun School of Public Health, Hadassah-Hebrew University, Jerusalem, Israel.
authors.forename: Ora
authors.initials: O
authors.lastname: Paltiel
authors.affiliation: Tissue Typing Laboratory, Hadassah Medical Center, Ein Karem, Jerusalem, 91120, Israel.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Israel
authors.affiliation: Department of Neurology and Laboratory of Neuroimmunology, and the Agnes-Ginges Center for Neurogenetics, Hadassah Medical Center, Hebrew University of Jerusalem, The faculty of Medicine, Israel. Electronic address: adembinsky@gmail.com.
authors.forename: Adi
authors.initials: A
authors.lastname: Vaknin-Dembinsky
mesh_terms: D000328:Adult; D000906:Antibodies / Q000097:blood*; D051401:Aquaporin 4 / Q000276:immunology*; D018912:Arabs; D005260:Female; D005787:Gene Frequency; D059866:HLA-DQ beta-Chains / Q000235:genetics*; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D007514:Islam; D007557:Israel / Q000453:epidemiology / Q000208:ethnology; D008297:Male; D008875:Middle Aged; D009471:Neuromyelitis Optica / Q000097:blood* / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D055815:Young Adult
chemical_list: C496030:AQP4 protein, human; D000906:Antibodies; D051401:Aquaporin 4; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D059811:HLA-DRB1 Chains
keywords: AQP4; HLA class 2; Multiple sclerosis (MS); Muslims Arabs; Neuromyelitis optica (NMO)