PMID- 27049564 OWN - NLM STAT- MEDLINE DCOM- 20160817 LR - 20220330 IS - 1872-8421 (Electronic) IS - 0165-5728 (Linking) VI - 293 DP - 2016 Apr 15 TI - Increased occurrence of anti-AQP4 seropositivity and unique HLA Class II associations with neuromyelitis optica (NMO), among Muslim Arabs in Israel. PG - 65-70 LID - S0165-5728(16)30028-5 [pii] LID - 10.1016/j.jneuroim.2016.02.006 [doi] AB - 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. CI - Copyright (c) 2016 Elsevier B.V. All rights reserved. FAU - Brill, Livnat AU - Brill L AD - 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. FAU - Mandel, Micha AU - Mandel M AD - Department of Statistics, The Hebrew University of Jerusalem, Mount Scopus, Jerusalem 91905, Israel. FAU - Karussis, Dimitrios AU - Karussis D AD - 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. FAU - Petrou, Panayiota AU - Petrou P AD - 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. FAU - Miller, Keren AU - Miller K AD - Tissue Typing Laboratory, Hadassah Medical Center, Ein Karem, Jerusalem, 91120, Israel. FAU - Ben-Hur, Tamir AU - Ben-Hur T AD - 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. FAU - Karni, Arnon AU - Karni A AD - Neuroimmunology Laboratory, Department of Neurology, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. FAU - Paltiel, Ora AU - Paltiel O AD - Department of Hematology, Braun School of Public Health, Hadassah-Hebrew University, Jerusalem, Israel. FAU - Israel, Shoshana AU - Israel S AD - Tissue Typing Laboratory, Hadassah Medical Center, Ein Karem, Jerusalem, 91120, Israel. FAU - Vaknin-Dembinsky, Adi AU - Vaknin-Dembinsky A AD - 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. LA - eng PT - Journal Article DEP - 20160215 PL - Netherlands TA - J Neuroimmunol JT - Journal of neuroimmunology JID - 8109498 RN - 0 (AQP4 protein, human) RN - 0 (Antibodies) RN - 0 (Aquaporin 4) RN - 0 (HLA-DQ beta-Chains) RN - 0 (HLA-DQB1 antigen) RN - 0 (HLA-DRB1 Chains) SB - IM MH - Adult MH - Antibodies/*blood MH - Aquaporin 4/*immunology MH - Arabs MH - Female MH - Gene Frequency MH - HLA-DQ beta-Chains/*genetics MH - HLA-DRB1 Chains/*genetics MH - Humans MH - Islam MH - Israel/epidemiology/ethnology MH - Male MH - Middle Aged MH - Neuromyelitis Optica/*blood/epidemiology/*genetics/immunology MH - Young Adult OTO - NOTNLM OT - AQP4 OT - HLA class 2 OT - Multiple sclerosis (MS) OT - Muslims Arabs OT - Neuromyelitis optica (NMO) EDAT- 2016/04/07 06:00 MHDA- 2016/08/18 06:00 CRDT- 2016/04/07 06:00 PHST- 2015/09/30 00:00 [received] PHST- 2016/01/24 00:00 [revised] PHST- 2016/02/08 00:00 [accepted] PHST- 2016/04/07 06:00 [entrez] PHST- 2016/04/07 06:00 [pubmed] PHST- 2016/08/18 06:00 [medline] AID - S0165-5728(16)30028-5 [pii] AID - 10.1016/j.jneuroim.2016.02.006 [doi] PST - ppublish SO - J Neuroimmunol. 2016 Apr 15;293:65-70. doi: 10.1016/j.jneuroim.2016.02.006. Epub 2016 Feb 15.