{"entity": "publication", "iuid": "19151bf6cd3a46fe9a3821034a044afa", "timestamp": "2026-09-28T11:16:24.224Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/19151bf6cd3a46fe9a3821034a044afa.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/19151bf6cd3a46fe9a3821034a044afa"}}, "title": "Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk.", "authors": [{"family": "Tengvall", "given": "Katarina", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/b8f6227041cc44b1bd163c99956bba78.json"}}, {"family": "Huang", "given": "Jesse", "initials": "J"}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C"}, {"family": "Kammer", "given": "Patrick", "initials": "P"}, {"family": "Bistr\u00f6m", "given": "Martin", "initials": "M"}, {"family": "Ayoglu", "given": "Burcu", "initials": "B"}, {"family": "Lima Bomfim", "given": "Izaura", "initials": "I"}, {"family": "Stridh", "given": "Pernilla", "initials": "P"}, {"family": "Butt", "given": "Julia", "initials": "J"}, {"family": "Brenner", "given": "Nicole", "initials": "N"}, {"family": "Michel", "given": "Angelika", "initials": "A"}, {"family": "Lundberg", "given": "Karin", "initials": "K"}, {"family": "Padyukov", "given": "Leonid", "initials": "L"}, {"family": "Lundberg", "given": "Ingrid E", "initials": "IE"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E"}, {"family": "Ernberg", "given": "Ingemar", "initials": "I"}, {"family": "Olafsson", "given": "Sigurgeir", "initials": "S"}, {"family": "Dilthey", "given": "Alexander T", "initials": "AT"}, {"family": "Hillert", "given": "Jan", "initials": "J"}, {"family": "Alfredsson", "given": "Lars", "initials": "L"}, {"family": "Sundstr\u00f6m", "given": "Peter", "initials": "P"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3db33fa3edb94febb8be7927a16838d0.json"}}, {"family": "Waterboer", "given": "Tim", "initials": "T"}, {"family": "Olsson", "given": "Tomas", "initials": "T"}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/044ff0f987a642c7aa2aef33fe1d7ecd.json"}}], "type": "clinical trial", "published": "2019-08-20", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "116", "issue": "34", "pages": "16955-16960", "issn-l": "0027-8424"}, "abstract": "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 \u00d7 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 HLA-DRB1*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.", "doi": "10.1073/pnas.1902623116", "pmid": "31375628", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC6708327"}, {"db": "pii", "key": "1902623116"}], "notes": [], "created": "2026-09-23T06:41:19.615Z", "modified": "2026-09-23T06:41:19.677Z"}