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  • Ayoglu, BurcuKTH,Science for Life Laboratory, SciLifeLab,Proteomik och nanobioteknologi (author)

Anoctamin 2 identified as an autoimmune target in multiple sclerosis

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-02-09
  • National Academy of Sciences of the USA,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:kth-183623
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-183623URI
  • https://doi.org/10.1073/pnas.1518553113DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133019359URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20160411Not a duplicate with DiVA 916997 or DiVA 1413466 
  • 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.

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  • Mitsios, NicholasKarolinska Institutet (author)
  • Kockum, IngridKarolinska Institutet (author)
  • Khademi, MohsenKarolinska Institutet (author)
  • Zandian, ArashKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u11qiehv (author)
  • Sjoberg, RonaldKTH,Science for Life Laboratory, SciLifeLab,Proteomik och nanobioteknologi(Swepub:kth)u1j1wpi6 (author)
  • Forsstrom, BjornKTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u11i5nju (author)
  • Bredenberg, Johan (author)
  • Bomfim, Izaura LimaKarolinska Institutet (author)
  • Holmgren, ErikKarolinska Institutet (author)
  • Gronlund, HansKarolinska Institutet (author)
  • Guerreiro-Cacais, Andre OrtliebKarolinska Institutet (author)
  • Abdelmagid, NadaKarolinska Institutet (author)
  • Uhlen, MathiasKTH,Science for Life Laboratory, SciLifeLab,Proteomik och nanobioteknologi(Swepub:kth)u1dulvmw (author)
  • Waterboer, Tim (author)
  • Alfredsson, LarsKarolinska Institutet (author)
  • Mulder, JanKarolinska Institutet (author)
  • Schwenk, Jochen M.KTH,Proteomik och nanobioteknologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1h7wtme (author)
  • Olsson, TomasKarolinska Institutet (author)
  • Nilsson, Peter (author)
  • KTHScience for Life Laboratory, SciLifeLab (creator_code:org_t)

Related titles

  • In:Proceedings of the National Academy of Sciences of the United States of America: National Academy of Sciences of the USA113:8, s. 2188-21930027-84241091-6490

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