T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression

Solmaz Yazdani, Christina Seitz, Can Cui, Anikó Lovik, Lu Pan, Fredrik Piehl, Yudi Pawitan, Ulf Kläppe, Rayomand Press, Kristin Samuelsson, Li Yin, Trung Nghia Vu, Anne-Laure Joly, Lisa S. Westerberg, Björn Evertsson, Caroline Ingre, John Andersson () and Fang Fang ()
Additional contact information
Solmaz Yazdani: Karolinska Institutet
Christina Seitz: Karolinska Institutet
Can Cui: Karolinska Institutet
Anikó Lovik: Karolinska Institutet
Lu Pan: Karolinska Institutet
Fredrik Piehl: Karolinska Institutet
Yudi Pawitan: Karolinska Institutet
Ulf Kläppe: Karolinska Institutet
Rayomand Press: Karolinska Institutet
Kristin Samuelsson: Karolinska Institutet
Li Yin: Karolinska Institutet
Trung Nghia Vu: Karolinska Institutet
Anne-Laure Joly: Karolinska Institutet
Lisa S. Westerberg: Karolinska Institutet
Björn Evertsson: Karolinska Institutet
Caroline Ingre: Karolinska Institutet
John Andersson: Karolinska Institutet
Fang Fang: Karolinska Institutet

Nature Communications, 2022, vol. 13, issue 1, 1-13

Abstract: Abstract Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, involving neuroinflammation and T cell infiltration in the central nervous system. However, the contribution of T cell responses to the pathology of the disease is not fully understood. Here we show, by flow cytometric analysis of blood and cerebrospinal fluid (CSF) samples of a cohort of 89 newly diagnosed ALS patients in Stockholm, Sweden, that T cell phenotypes at the time of diagnosis are good predictors of disease outcome. High frequency of CD4+FOXP3− effector T cells in blood and CSF is associated with poor survival, whereas high frequency of activated regulatory T (Treg) cells and high ratio between activated and resting Treg cells in blood are associated with better survival. Besides survival, phenotypic profiling of T cells could also predict disease progression rate. Single cell transcriptomics analysis of CSF samples shows clonally expanded CD4+ and CD8+ T cells in CSF, with characteristic gene expression patterns. In summary, T cell responses associate with and likely contribute to disease progression in ALS, supporting modulation of adaptive immunity as a viable therapeutic option.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34526-9

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DOI: 10.1038/s41467-022-34526-9

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