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Molecular mimicry b...
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Tengvall, Katarina,1980-Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
(author)
Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk
- Article/chapterEnglish2019
Publisher, publication year, extent ...
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2019-08-02
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NATL ACAD SCIENCES,2019
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-257803
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-257803URI
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https://doi.org/10.1073/pnas.1902623116DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-163063URI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-420921URI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:141630183URI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20190912
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Multiple sclerosis (MS) is a chronic inflammatory, likely autoimmune disease of the central nervous system with a combination of genetic and environmental risk factors, among which Epstein-Barr virus (EBV) infection is a strong suspect. We have previously identified increased autoantibody levels toward the chloride-channel protein Anoctamin 2 (ANO2) in MS. Here, IgG antibody reactivity toward ANO2 and EBV nuclear antigen 1 (EBNA1) was measured using bead-based multiplex serology in plasma samples from 8,746 MS cases and 7,228 controls. We detected increased anti-ANO2 antibody levels in MS (P = 3.5 x 10(-36)) with 14.6% of cases and 7.8% of controls being ANO2 seropositive (odds ratio [OR] = 1.6; 95% confidence intervals [95% CI]: 1.5 to 1.8). The MS risk increase in ANO2-seropositive individuals was dramatic when also exposed to 3 known risk factors for MS: HLA-DRB1*15: 01 carriage, absence of HLA-A*02: 01, and high anti-EBNA1 antibody levels (OR = 24.9; 95% CI: 17.9 to 34.8). Reciprocal blocking experiments with ANO2 and EBNA1 peptides demonstrated antibody cross-reactivity, mapping to ANO2 [aa 140 to 149] and EBNA1 [aa 431 to 440]. HLA gene region was associated with anti-ANO2 antibody levels and HLADRB1*04: 01 haplotype was negatively associated with ANO2 seropositivity (OR = 0.6; 95% CI: 0.5 to 0.7). Anti-ANO2 antibody levels were not increased in patients from 3 other inflammatory disease cohorts. The HLA influence and the fact that specific IgG production usually needs T cell help provides indirect evidence for a T cell ANO2 autoreactivity in MS. We propose a hypothesis where immune reactivity toward EBNA1 through molecular mimicry with ANO2 contributes to the etiopathogenesis of MS.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Huang, JesseKarolinska Inst, Karolinska Neuroimmunol & Multiple Sclerosis Ctr, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden.
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Hellström, CeciliaKTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1doy1fn
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Kammer, PatrickGerman Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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Biström, MartinUmeå universitet,Klinisk neurovetenskap,Umea Univ, Dept Pharmacol & Clin Neurosci, S-90185 Umea, Sweden.(Swepub:umu)manbim02
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Ayoglu, BurcuKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1kfjubd
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Bomfim, Izaura LimaKarolinska Inst, Karolinska Neuroimmunol & Multiple Sclerosis Ctr, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden.;Karolinska Univ Hosp, Ctr Mol Med, S-17176 Stockholm, Sweden.
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Stridh, PernillaKarolinska Institutet
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Butt, JuliaGerman Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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Brenner, NicoleGerman Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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Michel, AngelikaGerman Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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Lundberg, KarinKarolinska Institutet
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Padyukov, LeonidKarolinska Institutet
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Lundberg, Ingrid E.Karolinska Institutet
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Svenungsson, ElisabetKarolinska Institutet
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Ernberg, IngemarKarolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
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Olafsson, SigurgeirAmgen Inc, deCODE Genet, IS-101 Reykjavik, Iceland.
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Dilthey, Alexander T.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.;Heinrich Heine Univ Dusseldorf, Inst Med Microbiol & Hosp Hyg, D-40225 Dusseldorf, Germany.
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Hillert, JanKarolinska Institutet
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Alfredsson, LarsKarolinska Institutet
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Sundström, PeterUmeå universitet,Klinisk neurovetenskap,Umea Univ, Dept Pharmacol & Clin Neurosci, S-90185 Umea, Sweden.(Swepub:umu)pesu0002
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Nilsson, PeterKTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1ws88sk
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Waterboer, TimGerman Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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Olsson, TomasKarolinska Institutet
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Kockum, IngridKarolinska Institutet
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Uppsala universitetInstitutionen för medicinsk biokemi och mikrobiologi
(creator_code:org_t)
Related titles
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In:Proceedings of the National Academy of Sciences of the United States of America: NATL ACAD SCIENCES116:34, s. 16955-169600027-84241091-6490
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Tengvall, Katari ...
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Huang, Jesse
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Hellström, Cecil ...
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Kammer, Patrick
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Biström, Martin
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Ayoglu, Burcu
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Bomfim, Izaura L ...
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Stridh, Pernilla
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Butt, Julia
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Brenner, Nicole
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Michel, Angelika
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Lundberg, Karin
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Padyukov, Leonid
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Lundberg, Ingrid ...
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Svenungsson, Eli ...
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Ernberg, Ingemar
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Olafsson, Sigurg ...
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Dilthey, Alexand ...
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Hillert, Jan
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Alfredsson, Lars
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Sundström, Peter
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Nilsson, Peter
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Waterboer, Tim
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Olsson, Tomas
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Kockum, Ingrid
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