Immune Cell–Specific SMN Expression and Sustained Immune Alterations in Treated Spinal Muscular Atrophy

Ines Tapken; Katharina Rahmel-Stein; Christine Ehlers; Federica Cieri; Nora T. Detering; Tobias Schüning; Bogdan Bjelica; Charlotte Mindermann; Svenja Neuhoff; Linda-Isabell Schmitt; Markus Leo; Tim Hagenacker; Sabine Illsinger; Elia Di Schiavi; Theresa Graalmann; Susanne Petri; Ulrich Kalinke; Peter Claus

doi:10.1172/JCI203540

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Tapken, I. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Rahmel-Stein, K. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Ehlers, C. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Cieri, F. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Detering, N. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Schüning, T. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Bjelica, B. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Mindermann, C. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Neuhoff, S. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Schmitt, L. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Leo, M. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Hagenacker, T. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Illsinger, S. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Di Schiavi, E. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Graalmann, T. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Petri, S. in: PubMed | Google Scholar

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Kalinke, U. in: PubMed | Google Scholar |

¹TWINCORE–Centre for Experimental and Clinical Infection Research, Hannover, Germany

²Institute of Biosciences and BioResources, National Research Council (CNR), Naples, Italy

³Center for Systems Neuroscience (ZSN), Hannover, Germany

⁴PRACTIS Clinician Scientist Program, Dean's Office for Academic Career Deve, Hannover Medical School, Hannover, Germany

⁵Clinic for Pediatric Kidney-, Liver-, Metabolic and Neurological Diseases, Hannover Medical School, Hannover, Germany

⁶Department of Neurology, Center for Translational Neuro- and Behavioral Sci, University Medicine Essen, Essen, Germany

⁷Department of Neurology and Clinical Neurophysiology, Hannover Medical School, Hannover, Germany

Find articles by Claus, P. in: PubMed | Google Scholar |

J Clin Invest. https://doi.org/10.1172/JCI203540.
Copyright © 2026, Tapken et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

Published August 25, 2026 - Version history

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 impact of SMN-modulating therapies on the immune system remains underexplored. We found that in neonatal mouse spleen, SMN expression was highest in B cells, which were massively reduced in SMA mice. In human PBMCs from adults, DCs and monocytes expressed the highest SMN levels, whereas SMA patients showed reduced DC and increased B cell frequencies. Patients receiving systemic versus CNS-restricted therapy showed similar differences in immune cell composition and SMN levels. Similarly, an exploratory cohort including untreated patients did not indicate a substantial treatment-specific effect relative to controls. To assess the impact of differentiation on SMN, PMA-treated THP-1 cells were analyzed, revealing enhanced aberrant SMN splicing and increased SMN-positive Cajal bodies. In conclusion, SMN levels vary across immune cell types, and reduced SMN levels are associated with altered immune cell composition. Immune alterations and decreased SMN levels were observed in both treated and untreated SMA patients and may contribute to dysfunctions of the immune system in SMA.

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Immune Cell–Specific SMN Expression and Sustained Immune Alterations in Treated Spinal Muscular Atrophy

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Immune Cell–Specific SMN Expression and Sustained Immune Alterations in Treated Spinal Muscular Atrophy

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