Identification of four novel T cell autoantigens and personal autoreactive profiles in multiple sclerosis.


Journal

Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440

Informations de publication

Date de publication:
29 Apr 2022
Historique:
entrez: 27 4 2022
pubmed: 28 4 2022
medline: 28 4 2022
Statut: ppublish

Résumé

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

Identifiants

pubmed: 35476434
doi: 10.1126/sciadv.abn1823
pmc: PMC9045615
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

eabn1823

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Auteurs

Mattias Bronge (M)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Klara Asplund Högelin (KA)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Olivia G Thomas (OG)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Sabrina Ruhrmann (S)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Claudia Carvalho-Queiroz (C)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Ola B Nilsson (OB)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Andreas Kaiser (A)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Manuel Zeitelhofer (M)

Division of Vascular Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden.

Erik Holmgren (E)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Mathias Linnerbauer (M)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Milena Z Adzemovic (MZ)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Cecilia Hellström (C)

Division of Affinity Proteomics, Department of Protein Science, SciLifeLab, KTH-Royal Institute of Technology, 171 65 Solna, Sweden.

Ivan Jelcic (I)

Neuroimmunology and MS Research Section (NIMS), Neurology Clinic, University of Zürich, University Hospital Zürich, 8091 Zürich, Switzerland.

Hao Liu (H)

Department of Protein Science, KTH-Royal Institute of Technology, 114 21 Stockholm, Sweden.

Peter Nilsson (P)

Division of Affinity Proteomics, Department of Protein Science, SciLifeLab, KTH-Royal Institute of Technology, 171 65 Solna, Sweden.

Jan Hillert (J)

Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Lou Brundin (L)

Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Katharina Fink (K)

Department of Clinical Neuroscience, Division of Neurology, Karolinska Institutet, Karolinska University Hospital, 171 76 Stockholm, Sweden.

Ingrid Kockum (I)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Katarina Tengvall (K)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.
Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, 752 37 Uppsala, Sweden.

Roland Martin (R)

Neuroimmunology and MS Research Section (NIMS), Neurology Clinic, University of Zürich, University Hospital Zürich, 8091 Zürich, Switzerland.

Hanna Tegel (H)

Human Protein Atlas, Department of Protein Science, KTH-Royal Institute of Technology, Stockholm, Sweden.

Torbjörn Gräslund (T)

Department of Protein Science, KTH-Royal Institute of Technology, 114 21 Stockholm, Sweden.

Faiez Al Nimer (F)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

André Ortlieb Guerreiro-Cacais (AO)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Mohsen Khademi (M)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Guro Gafvelin (G)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Tomas Olsson (T)

Neuroimmunology Unit, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institutet, 171 76 Stockholm, Sweden.

Hans Grönlund (H)

Therapeutic Immune Design, Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, 171 76 Stockholm, Sweden.

Classifications MeSH