Anoctamin 2 identified as an autoimmune target in multiple sclerosis
2016 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 113, no 8, 2188-2193 p.Article in journal (Refereed) PublishedText
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.
Place, publisher, year, edition, pages
National Academy of Sciences of the USA , 2016. Vol. 113, no 8, 2188-2193 p.
multiple sclerosis, autoimmunity, autoantibodies, protein microarrays, affinity proteomics
IdentifiersURN: urn:nbn:se:kth:diva-183623DOI: 10.1073/pnas.1518553113ISI: 000370620300067PubMedID: 26862169ScopusID: 2-s2.0-84959220664OAI: oai:DiVA.org:kth-183623DiVA: diva2:918410
FunderKnut and Alice Wallenberg FoundationAFA InsuranceScience for Life Laboratory - a national resource center for high-throughput molecular bioscienceSwedish Research CouncilThe Swedish Brain Foundation
QC 201604112016-04-112016-03-182016-04-11Bibliographically approved