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Molecular mimicry b...
Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk
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- Tengvall, Katarina, 1980- (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Huang, Jesse (author)
- Karolinska 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, Cecilia (author)
- KTH,Proteinvetenskap,Science for Life Laboratory, SciLifeLab
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- Kammer, Patrick (author)
- German Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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- Biström, Martin (author)
- Umeå universitet,Klinisk neurovetenskap,Umea Univ, Dept Pharmacol & Clin Neurosci, S-90185 Umea, Sweden.
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- Ayoglu, Burcu (author)
- KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
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- Bomfim, Izaura Lima (author)
- Karolinska 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, Pernilla (author)
- Karolinska Institutet
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- Butt, Julia (author)
- German Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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- Brenner, Nicole (author)
- German Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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- Michel, Angelika (author)
- German Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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- Lundberg, Karin (author)
- Karolinska Institutet
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- Padyukov, Leonid (author)
- Karolinska Institutet
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- Lundberg, Ingrid E. (author)
- Karolinska Institutet
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- Svenungsson, Elisabet (author)
- Karolinska Institutet
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- Ernberg, Ingemar (author)
- Karolinska Inst, Dept Microbiol Tumor & Cell Biol, S-17177 Stockholm, Sweden.
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- Olafsson, Sigurgeir (author)
- Amgen Inc, deCODE Genet, IS-101 Reykjavik, Iceland.
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- Dilthey, Alexander T. (author)
- 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, Jan (author)
- Karolinska Institutet
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- Alfredsson, Lars (author)
- Karolinska Institutet
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- Sundström, Peter (author)
- Umeå universitet,Klinisk neurovetenskap,Umea Univ, Dept Pharmacol & Clin Neurosci, S-90185 Umea, Sweden.
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- Nilsson, Peter (author)
- KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
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- Waterboer, Tim (author)
- German Canc Res Ctr, Infect & Canc Epidemiol Infect Inflammat & Canc R, D-69120 Heidelberg, Germany.
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- Olsson, Tomas (author)
- Karolinska Institutet
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- Kockum, Ingrid (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-08-02
- 2019
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : NATL ACAD SCIENCES. - 0027-8424 .- 1091-6490. ; 116:34, s. 16955-16960
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Abstract
Subject headings
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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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Keyword
- Anoctamin 2
- ANO2
- multiple sclerosis
- molecular mimicry
- Epstein-Barr virus
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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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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show more...
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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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show less...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Neurology
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Proceedings of t ...
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Royal Institute of Technology
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Umeå University
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Uppsala University
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Karolinska Institutet