Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis
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-γ 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
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| Enthalten in: |
Science advances - 8(2022), 17 vom: 29. Apr., Seite eabn1823 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Bronge, Mattias [VerfasserIn] |
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| Anmerkungen: |
Date Revised 16.07.2022 published: Print-Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1126/sciadv.abn1823 |
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| PPN (Katalog-ID): |
NLM340053828 |
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| 245 | 1 | 0 | |a Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis |
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| 500 | |a Date Revised 16.07.2022 | ||
| 500 | |a published: Print-Electronic | ||
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| 520 | |a 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-γ 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 | ||
| 650 | 4 | |a Journal Article | |
| 700 | 1 | |a Högelin, Klara Asplund |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Olivia G |e verfasserin |4 aut | |
| 700 | 1 | |a Ruhrmann, Sabrina |e verfasserin |4 aut | |
| 700 | 1 | |a Carvalho-Queiroz, Claudia |e verfasserin |4 aut | |
| 700 | 1 | |a Nilsson, Ola B |e verfasserin |4 aut | |
| 700 | 1 | |a Kaiser, Andreas |e verfasserin |4 aut | |
| 700 | 1 | |a Zeitelhofer, Manuel |e verfasserin |4 aut | |
| 700 | 1 | |a Holmgren, Erik |e verfasserin |4 aut | |
| 700 | 1 | |a Linnerbauer, Mathias |e verfasserin |4 aut | |
| 700 | 1 | |a Adzemovic, Milena Z |e verfasserin |4 aut | |
| 700 | 1 | |a Hellström, Cecilia |e verfasserin |4 aut | |
| 700 | 1 | |a Jelcic, Ivan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Nilsson, Peter |e verfasserin |4 aut | |
| 700 | 1 | |a Hillert, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Brundin, Lou |e verfasserin |4 aut | |
| 700 | 1 | |a Fink, Katharina |e verfasserin |4 aut | |
| 700 | 1 | |a Kockum, Ingrid |e verfasserin |4 aut | |
| 700 | 1 | |a Tengvall, Katarina |e verfasserin |4 aut | |
| 700 | 1 | |a Martin, Roland |e verfasserin |4 aut | |
| 700 | 1 | |a Tegel, Hanna |e verfasserin |4 aut | |
| 700 | 1 | |a Gräslund, Torbjörn |e verfasserin |4 aut | |
| 700 | 1 | |a Al Nimer, Faiez |e verfasserin |4 aut | |
| 700 | 1 | |a Guerreiro-Cacais, André Ortlieb |e verfasserin |4 aut | |
| 700 | 1 | |a Khademi, Mohsen |e verfasserin |4 aut | |
| 700 | 1 | |a Gafvelin, Guro |e verfasserin |4 aut | |
| 700 | 1 | |a Olsson, Tomas |e verfasserin |4 aut | |
| 700 | 1 | |a Grönlund, Hans |e verfasserin |4 aut | |
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