Evidence map›Paper›PMID 26862169›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Anoctamin 2 identified as an autoimmune target in multiple sclerosis.

Burcu Ayoglu, Nicholas Mitsios, Ingrid Kockum, Mohsen Khademi, Arash Zandian, Ronald Sjöberg, Björn Forsström, Johan Bredenberg, Izaura Lima Bomfim, Erik Holmgren and 10 more

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 2 pooled it
7.0field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 2 syntheses or guidelines pooled it, 111 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk.Proceedings of the National Academy of Sciences of the United States of America · 2019
    Trial
  5. Review
  6. Article
  7. Review
  8. Review
  9. Multiple molecular mimics in Epstein Barr Nuclear Antigen-1, and the pathogenesis of multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. Antibody reactivity against EBNA1 and GlialCAM differentiates multiple sclerosis patients from healthy controls.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  14. Article
  15. TMEM16 proteins: CaInternational journal of molecular medicine · 2024
    Review
  16. Article
  17. Article
  18. Article
  19. T cell help shapes B cell tolerance.Science immunology · 2024
    Article
  20. A Blood Test for the Diagnosis of Multiple Sclerosis.International journal of molecular sciences · 2024
    Article

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors at 5 institutions in 2 countries.

Burcu AyogluAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden; burcu@kth.se.
Nicholas MitsiosAffinity Proteomics, Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-17165 Stockholm, Sweden;
Ingrid KockumNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Mohsen KhademiNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Arash ZandianAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Ronald SjöbergAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Björn ForsströmAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Johan BredenbergAffinity Proteomics, Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-17165 Stockholm, Sweden;
Izaura Lima BomfimNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Erik HolmgrenTherapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Hans GrönlundTherapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
André Ortlieb Guerreiro-CacaisNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Nada AbdelmagidNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Mathias UhlénAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Tim WaterboerInfection and Cancer Program, German Cancer Research Center, 69120 Heidelberg, Germany;
Lars AlfredssonInstitute of Environmental Medicine, Karolinska Institute, SE-17177 Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, SE-11365 Stockholm, Sweden.
Jan MulderAffinity Proteomics, Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-17165 Stockholm, Sweden;
Jochen M SchwenkAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Tomas OlssonNeuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
Peter NilssonAffinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
Karolinska Institutet · SEScience for Life Laboratory · SEKTH Royal Institute of Technology · SEGerman Cancer Research Center · DEStockholm County Council · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple sclerosis (MS) is the most common chronic inflammatory disease of the central nervous system and also is regarded as an autoimmune condition. However, the antigenic targets of the autoimmune response in MS have not yet been deciphered. In an effort to mine the autoantibody repertoire within MS, we profiled 2,169 plasma samples from MS cases and population-based controls using bead arrays built with 384 human protein fragments selected from an initial screening with 11,520 antigens. Our data revealed prominently increased autoantibody reactivity against the chloride-channel protein anoctamin 2 (ANO2) in MS cases compared with controls. This finding was corroborated in independent assays with alternative protein constructs and by epitope mapping with peptides covering the identified region of ANO2. Additionally, we found a strong interaction between the presence of ANO2 autoantibodies and the HLA complex MS-associated DRB1*15 allele, reinforcing a potential role for ANO2 autoreactivity in MS etiopathogenesis. Furthermore, immunofluorescence analysis in human MS brain tissue showed ANO2 expression as small cellular aggregates near and inside MS lesions. Thus this study represents one of the largest efforts to characterize the autoantibody repertoire within MS. The findings presented here demonstrate that an ANO2 autoimmune subphenotype may exist in MS and lay the groundwork for further studies focusing on the pathogenic role of ANO2 autoantibodies in MS.

Indexed as

AdolescentAdultAgedAnoctaminsAutoantibodiesAutoantigensBrainCase-Control StudiesChloride ChannelsEpitope MappingFemaleHLA-DRB1 ChainsHumansImmunohistochemistryMaleMembrane ProteinsANO2 protein, humanAnoctaminsAutoantibodiesAutoantigensChloride ChannelsHLA-DRB1*15 antigenHLA-DRB1 ChainsMembrane ProteinsPeptide Fragmentsaffinity proteomicsautoantibodiesautoimmunitymultiple sclerosisprotein microarrays

Identifiers

PMID26862169
PMCPMC4776531
OpenAlexW2255924482

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.