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Peer-reviewedCC BY 4.0The Journal of Clinical Investigation

Immune cell–specific SMN expression and sustained immune alterations in treated spinal muscular atrophy

  • Ines Tapken1,2,3,4
  • Katharina Rahmel-Stein1,5
  • Christine Ehlers1,6
  • Federica Cieri7,8
  • Nora T. Detering9
  • Tobias Schüning9
  • Bogdan Bjelica10,11
  • Charlotte Mindermann12
  • Svenja Neuhoff13
  • Linda-Isabell Schmitt13
  • Markus Leo13
  • Tim Hagenacker13
6 more authors
  • Sabine Illsinger12
  • Elia Di Schiavi7
  • Theresa Graalmann1,6,14
  • Susanne Petri11,15
  • Ulrich Kalinke1,4
  • Peter Claus8,16
16 affiliations
  1. 1TWINCORE–Centre for Experimental and Clinical Infection Research, a joint venture between the Hannover Medical School and the Helmholtz Centre for Infection Research, Hannover, Germany.
  2. 2Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz Centre for Infection Research and Hannover Medical School, Hannover, Germany.
  3. 3Department of Gastroenterology, Hepatology, Infectious Diseases and Endocrinology, and
  4. 4Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany.
  5. 5Hannover Biomedical Research School (HBRS) and Center for Infection Biology (ZIB), Hannover, Germany.
  6. 6Biomedical Research in End-Stage and Obstructive Lung Disease Hannover (BREATH), German Center for Lung Research (DZL), Hannover, Germany.
  7. 7Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy.
  8. 8Department of Biology, University of Naples Federico II, Naples, Italy.
  9. 9Center for Systems Neuroscience (ZSN), Hannover, Germany.
  10. 10PRACTIS Clinician Scientist Program, Dean’s Office for Academic Career Development, and
  11. 11Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany
  12. 12Clinic for Pediatric Kidney, Liver, Metabolic, and Neurological Diseases, Hannover Medical School, Hannover, Germany.
  13. 13Department of Neurology, Center for Translational Neuro- and Behavioral Sciences (C-TNBS), University Medicine Essen, Essen, Germany.
  14. 14Department of Rheumatology and Immunology, Hannover Medical School, Hannover, Germany.
  15. 15DIAKOVERE Henriettenstift, Clinic for Neurology and Clinical Neurophysiology, Hannover, Germany.
  16. 16Laboratory of Molecular Neurosciences, Department of Psychiatry, Social Psychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany.
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Abstract

Mutations in the survival of motor neuron 1 (SMN1) can reduce functional SMN protein levels, which causes spinal muscular atrophy (SMA), a disease affecting the nervous system and peripheral tissues, including the immune system. Yet, SMN expression across immune cell subsets and the effect of SMN-modulating therapies on the immune system remain underexplored. We found that in neonatal mouse spleens, SMN expression was highest in B cells, and was massively reduced in SMA mice. In human PBMCs from adults, DCs and monocytes expressed the highest SMN levels, whereas patients with SMA showed reduced DC frequencies and increased B cell frequencies. Patients receiving systemic versus CNS-restricted therapy showed similar differences in immune cell composition and SMN expression levels. Similarly, an exploratory cohort including untreated patients did not show a substantial treatment-specific effect relative to controls. To assess the effect of differentiation on SMN, we analyzed PMA-treated THP-1 cells and found enhanced aberrant SMN splicing and increased SMN+ Cajal bodies. SMN levels varied across immune cell types, and reduced SMN levels were associated with altered immune cell composition. Immune alterations and decreased SMN levels were observed in both treated and untreated patients with SMA and may have contributed to dysfunctions of the immune system.

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Cite

BibTeXRIS
BibTeX
@article{tapken2026immune,
  title = {{Immune cell–specific SMN expression and sustained immune alterations in treated spinal muscular atrophy}},
  author = {Ines Tapken and Katharina Rahmel-Stein and Christine Ehlers and Federica Cieri and Nora T. Detering and Tobias Schüning and Bogdan Bjelica and Charlotte Mindermann and Svenja Neuhoff and Linda-Isabell Schmitt and Markus Leo and Tim Hagenacker and Sabine Illsinger and Elia Di Schiavi and Theresa Graalmann and Susanne Petri and Ulrich Kalinke and Peter Claus},
  journal = {The Journal of Clinical Investigation},
  year = {2026},
  month = aug,
  doi = {10.1172/jci203540},
  url = {https://doi.org/10.1172/jci203540},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Immune cell–specific SMN expression and sustained immune alterations in treated spinal muscular atrophy
AU  - Ines Tapken
AU  - Katharina Rahmel-Stein
AU  - Christine Ehlers
AU  - Federica Cieri
AU  - Nora T. Detering
AU  - Tobias Schüning
AU  - Bogdan Bjelica
AU  - Charlotte Mindermann
AU  - Svenja Neuhoff
AU  - Linda-Isabell Schmitt
AU  - Markus Leo
AU  - Tim Hagenacker
AU  - Sabine Illsinger
AU  - Elia Di Schiavi
AU  - Theresa Graalmann
AU  - Susanne Petri
AU  - Ulrich Kalinke
AU  - Peter Claus
PY  - 2026
DA  - 2026/08/25
JO  - The Journal of Clinical Investigation
DO  - 10.1172/jci203540
UR  - https://doi.org/10.1172/jci203540
AB  - Mutations in the survival of motor neuron 1 (SMN1) can reduce functional SMN protein levels, which causes spinal muscular atrophy (SMA), a disease affecting the nervous system and peripheral tissues, including the immune system. Yet, SMN expression across immune cell subsets and the effect of SMN-modulating therapies on the immune system remain underexplored. We found that in neonatal mouse spleens, SMN expression was highest in B cells, and was massively reduced in SMA mice. In human PBMCs from adults, DCs and monocytes expressed the highest SMN levels, whereas patients with SMA showed reduced DC frequencies and increased B cell frequencies. Patients receiving systemic versus CNS-restricted therapy showed similar differences in immune cell composition and SMN expression levels. Similarly, an exploratory cohort including untreated patients did not show a substantial treatment-specific effect relative to controls. To assess the effect of differentiation on SMN, we analyzed PMA-treated THP-1 cells and found enhanced aberrant SMN splicing and increased SMN+ Cajal bodies. SMN levels varied across immune cell types, and reduced SMN levels were associated with altered immune cell composition. Immune alterations and decreased SMN levels were observed in both treated and untreated patients with SMA and may have contributed to dysfunctions of the immune system.
SN  - 0021-9738
SN  - 1558-8238
ER  -