Authors: Mattias Bronge, Klara Asplund Högelin, Olivia G. Thomas, Sabrina Ruhrmann, Claudia Carvalho-Queiroz, Ola B. Nilsson, Andreas Kaiser, Manuel Zeitelhofer, Erik Holmgren, Mathias Linnerbauer, Milena Z. Adzemovic, Cecilia Hellström, Ivan Jelcic, Hao Liu, Peter Nilsson, Jan Hillert, Lou Brundin, Katharina Fink, Ingrid Kockum, Katarina Tengvall, Roland Martin, Hanna Tegel, Torbjörn Gräslund, Faiez Al Nimer, André Ortlieb Guerreiro-Cacais, Mohsen Khademi, Guro Gafvelin, Tomas Olsson, Hans Grönlund
Published: 2022-04-27
Source: Full article
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