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

被引：27

作者：

Bronge, Mattias ^{[1
]}

Hogelin, Klara Asplund ^{[2
]}

Thomas, Olivia G. ^{[1
]}

Ruhrmann, Sabrina ^{[1
]}

Carvalho-Queiroz, Claudia ^{[1
]}

Nilsson, Ola B. ^{[1
]}

Kaiser, Andreas ^{[1
]}

Zeitelhofer, Manuel ^{[3
]}

Holmgren, Erik ^{[1
]}

Linnerbauer, Mathias ^{[2
]}

Adzemovic, Milena Z. ^{[2
]}

Hellstrom, Cecilia ^{[4
]}

Jelcic, Ivan ^{[5
]}

Liu, Hao ^{[6
]}

Nilsson, Peter ^{[4
]}

Hillert, Jan ^{[7
]}

Brundin, Lou ^{[7
]}

Fink, Katharina ^{[7
]}

Kockum, Ingrid ^{[2
]}

Tengvall, Katarina ^{[2
,8
]}

Martin, Roland ^{[5
]}

Tegel, Hanna ^{[9
]}

Graslund, Torbjorn ^{[6
]}

Al Nimer, Faiez ^{[2
]}

Guerreiro-Cacais, Andre Ortlieb ^{[2
]}

Khademi, Mohsen ^{[2
]}

Gafvelin, Guro ^{[1
]}

Olsson, Tomas ^{[2
]}

Gronlund, Hans ^{[1
]}

机构：

[1] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Therapeut Immune Design, S-17176 Stockholm, Sweden

[2] Karolinska Inst, Ctr Mol Med, Dept Clin Neurosci, Neuroimmunol Unit, S-17176 Stockholm, Sweden

[3] Karolinska Inst, Dept Med Biochem & Biophys, Div Vasc Biol, S-17177 Stockholm, Sweden

[4] KTH Royal Inst Technol, Dept Prot Sci, Div Affin Prote, SciLifeLab, S-17165 Solna, Sweden

[5] Univ Zurich, Univ Hosp Zurich, Neuroimmunol & MS Res Sect NIMS, Neurol Clin, CH-8091 Zurich, Switzerland

[6] KTH Royal Inst Technol, Dept Prot Sci, S-11421 Stockholm, Sweden

[7] Karolinska Inst, Karolinska Univ Hosp, Dept Clin Neurosci, Div Neurol, S-17176 Stockholm, Sweden

[8] Uppsala Univ, Dept Med Biochem & Microbiol, Sci Life Lab, S-75237 Uppsala, Sweden

[9] KTH Royal Inst Technol, Dept Prot Sci, Human Prot Atlas, Stockholm, Sweden

来源：

SCIENCE ADVANCES | 2022年 / 8卷 / 17期

基金：

瑞典研究理事会;

关键词：

MYELIN-OLIGODENDROCYTE GLYCOPROTEIN; ADAPTIVE IMMUNE-RESPONSES; PROTEIN EPITOPES; CIRCADIAN-RHYTHM; TARGET ANTIGENS; CLINICAL-TRIAL; THERAPY; SEARCH; INNATE; DETERMINANTS;

D O I：

10.1126/sciadv.abn1823

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：18

共 76 条

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