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

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.

Ingår i:Nature communications: Springer Science and Business Media LLC13:1, s. 6733-2041-1723

Av författaren/redakt...: Yazdani, S; Seitz, C; Cui, C; Lovik, A; Pan, L; Piehl, F; visa fler...; Pawitan, Y; Klappe, U; Press, R; Samuelsson, K; Yin, L; Vu, TN; Joly, AL; Westerberg, LS; Evertsson, B; Ingre, C; Andersson, J; Fang, F; visa färre...

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