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

Author

Listed:
  • Solmaz Yazdani

    (Karolinska Institutet)

  • Christina Seitz

    (Karolinska Institutet)

  • Can Cui

    (Karolinska Institutet)

  • Anikó Lovik

    (Karolinska Institutet)

  • Lu Pan

    (Karolinska Institutet)

  • Fredrik Piehl

    (Karolinska Institutet
    Karolinska University Hospital)

  • Yudi Pawitan

    (Karolinska Institutet)

  • Ulf Kläppe

    (Karolinska Institutet
    Karolinska University Hospital)

  • Rayomand Press

    (Karolinska Institutet
    Karolinska University Hospital)

  • Kristin Samuelsson

    (Karolinska Institutet
    Karolinska University Hospital)

  • Li Yin

    (Karolinska Institutet)

  • Trung Nghia Vu

    (Karolinska Institutet)

  • Anne-Laure Joly

    (Karolinska Institutet)

  • Lisa S. Westerberg

    (Karolinska Institutet)

  • Björn Evertsson

    (Karolinska Institutet
    Karolinska University Hospital)

  • Caroline Ingre

    (Karolinska Institutet
    Karolinska University Hospital)

  • John Andersson

    (Karolinska Institutet)

  • Fang Fang

    (Karolinska Institutet)

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.

Suggested Citation

  • 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, 2022. "T cell responses at diagnosis of amyotrophic lateral sclerosis predict disease progression," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34526-9
    DOI: 10.1038/s41467-022-34526-9
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    Cited by:

    1. Stanislav Tsitkov & Kelsey Valentine & Velina Kozareva & Aneesh Donde & Aaron Frank & Susan Lei & Jennifer Eyk & Steve Finkbeiner & Jeffrey D. Rothstein & Leslie M. Thompson & Dhruv Sareen & Clive N. , 2024. "Disease related changes in ATAC-seq of iPSC-derived motor neuron lines from ALS patients and controls," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    2. I-Na Lu & Phyllis Fung-Yi Cheung & Michael Heming & Christian Thomas & Giovanni Giglio & Markus Leo & Merve Erdemir & Timo Wirth & Simone König & Christine A. Dambietz & Christina B. Schroeter & Chris, 2024. "Cell-mediated cytotoxicity within CSF and brain parenchyma in spinal muscular atrophy unaltered by nusinersen treatment," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. Jessica Mandrioli & Roberto D’Amico & Elisabetta Zucchi & Sara De Biasi & Federico Banchelli & Ilaria Martinelli & Cecilia Simonini & Domenico Lo Tartaro & Roberto Vicini & Nicola Fini & Giulia Gianfe, 2023. "Randomized, double-blind, placebo-controlled trial of rapamycin in amyotrophic lateral sclerosis," Nature Communications, Nature, vol. 14(1), pages 1-14, December.

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