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Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis
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- Bronge, Mattias (author)
- Karolinska Institutet
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- Hogelin, Klara Asplund (author)
- Karolinska Institutet
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- Thomas, Olivia G. (author)
- Karolinska Institutet
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- Karolinska Institutet Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden (creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2022
- 2022
- English.
- In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:17
- Journal article (peer-reviewed)
Abstract
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- Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS), in which pathological T cells, likely autoimmune, play a key role. Despite its central importance, the autoantigen repertoire remains largely uncharacterized. Using a novel in vitro antigen delivery method combined with the Human Protein Atlas library, we screened for T cell autoreactivity against 63 CNS-expressed proteins. We identified four previously unreported autoantigens in MS: fatty acid-binding protein 7, prokineticin-2, reticulon-3, and synaptosomal-associated protein 91, which were verified to induce interferon-gamma responses in MS in two cohorts. Autoreactive profiles were heterogeneous, and reactivity to several autoantigens was MS-selective. Autoreactive T cells were predominantly CD4(+) and human leukocyte antigen-DR restricted. Mouse immunization induced antigen-specific responses and CNS leukocyte infiltration. This represents one of the largest systematic efforts to date in the search for MS autoantigens, demonstrates the heterogeneity of autoreactive profiles, and highlights promising targets for future diagnostic tools and immunomodulatory therapies in MS.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Immunologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Immunology in the medical area (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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