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

• Published in: Nature communications Vol. 13; no. 1; pp. 6733 - 13
• Main Authors: Yazdani, Solmaz, Seitz, Christina, Cui, Can, Lovik, Anikó, Pan, Lu, Piehl, Fredrik, Pawitan, Yudi, Kläppe, Ulf, Press, Rayomand, Samuelsson, Kristin, Yin, Li, Vu, Trung Nghia, Joly, Anne-Laure, Westerberg, Lisa S, Evertsson, Björn, Ingre, Caroline, Andersson, John, Fang, Fang
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 08.11.2022; Nature Publishing Group UK; Nature Portfolio
• Subjects: Adaptive immunity; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - diagnosis; Amyotrophic Lateral Sclerosis - genetics; Amyotrophic Lateral Sclerosis - pathology; Blood; CD4 antigen; CD8 antigen; CD8-Positive T-Lymphocytes - pathology; Central nervous system; Cerebrospinal fluid; Diagnosis; Disease Progression; Effector cells; Flow cytometry; Foxp3 protein; Gene expression; High frequencies; Humans; Immune system; Infiltration; Inflammation; Lymphocytes; Lymphocytes T; Medicin och hälsovetenskap; Nervous system; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Pathology; Phenotypes; Survival; T-Lymphocytes, Regulatory; Transcriptomics
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-34526-9

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.