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Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2188-93. doi: 10.1073/pnas.1518553113. Epub 2016 Feb 9.

Anoctamin 2 identified as an autoimmune target in multiple sclerosis.

Author information

1
Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden; burcu@kth.se.
2
Affinity Proteomics, Science for Life Laboratory, Department of Neuroscience, Karolinska Institute, SE-17165 Stockholm, Sweden;
3
Neuroimmunology Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
4
Affinity Proteomics, Science for Life Laboratory, School of Biotechnology, Royal Institute of Technology (KTH), SE-17165 Stockholm, Sweden;
5
Therapeutic Immune Design Unit, Department of Clinical Neuroscience, Karolinska Institute, SE-17177 Stockholm, Sweden;
6
Infection and Cancer Program, German Cancer Research Center, 69120 Heidelberg, Germany;
7
Institute of Environmental Medicine, Karolinska Institute, SE-17177 Stockholm, Sweden; Centre for Occupational and Environmental Medicine, Stockholm County Council, SE-11365 Stockholm, Sweden.

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.

KEYWORDS:

affinity proteomics; autoantibodies; autoimmunity; multiple sclerosis; protein microarrays

PMID:
26862169
PMCID:
PMC4776531
DOI:
10.1073/pnas.1518553113
[Indexed for MEDLINE]
Free PMC Article

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