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Autologous hematopoietic stem cell transplantation in a patient with multi-refractory stiff person syndrome

Bone Marrow Transplantation volume 60, pages 86–88 (2025)Cite this article

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Stiff person syndrome (SPS) is a rare neurological autoimmune disease (AD) with a prevalence of 1-2 patients per million, predominantly observed in women (2-3 females:1 man) [1, 2]. It is characterized by progressive stiffness of skeletal muscles, episodic painful muscle spasms, and prevention of volitional movements and ambulation in severe cases. Lumbar para-spinal rigidity limits the range of body mobility. Spasms due to increased muscle stiffness occur spontaneously or secondarily to different external and internal stimuli [1, 2].

Recent progress in the understanding of SPS pathophysiology support the predominant theory based on the immune-mediated interference of inhibitory signaling leading to nervous system hyperexcitability [1, 2]. It is a widely accepted hypothesis that an inhibitory effect on glutamic acid decarboxylase (GAD65) by anti-GAD65 antibodies blocks gamma-aminobutyric acid (GABA) synthesis and reduces the uptake of GABA in synaptic vesicles and thereby synaptic GABA release. Decreased synthesis of GABA results in decreased GABAergic transmission, leading to a state of neuronal hyperexcitability [3]. On the other hand, the autoantibody anti-glycine receptor alpha-1 subunit (GlyRα1) binds directly to motor neurons in the spinal cord and brainstem leading to motor neuron hyperactivity. This proposed mechanism was further supported by the demonstration that …human GlyR-immunoglobulin G (IgG), which disrupts inhibitory neurotransmission in cultured rodent motor neurons showing direct antagonistic actions on the glycine receptor [4]. However, the exact pathological role of anti-GAD and anti-GlyRα1 in humans is unknown, and different associated antibodies (anti-amphiphysin, dipeptidyl peptidase-like protein 6 (DPPX) and gephyrin) likely reflect different underlying pathophysiologic mechanisms [3]. It has also been suggested that GlyRα1-positive SPS may be more immunotherapy-responsive compared with patients with GAD65-positive SPS [5].

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Authors and Affiliations

  1. Sorbonne University, Paris, France

    Tamim Alsuliman, Nicolas Stocker, Simona Sestili, Anne Banet, Zoé Van de Wyngaert, Agnès Bonnin, Mohamad Mohty & Zora Marjanovic

  2. Service d’Hématologie Clinique et Thérapie Cellulaire, Hôpital Saint-Antoine, AP-HP, Paris, France

    Tamim Alsuliman, Nicolas Stocker, Simona Sestili, Anne Banet, Zoé Van de Wyngaert, Agnès Bonnin, Mohamad Mohty & Zora Marjanovic

  3. INSERM, UMRs 938, Centre de Recherche Saint-Antoine, Paris, France

    Tamim Alsuliman, Nicolas Stocker, Simona Sestili, Anne Banet, Zoé Van de Wyngaert, Agnès Bonnin, Mohamad Mohty & Zora Marjanovic

  4. Neuro-oncology Department, Hospital Group Pitié-Salpêtrière, AP-HP, Paris, France

    Dimitri Psimaras

  5. Institute of Neurology, Unité INSERM U1127, CNRS UMR 7225 (Institut du Cerveau et de la Moelle épinière) and OncoNeuroTox Group, Center for Patients With Neurological Complications of Oncologic Treatments, Hôpitaux Universitaires la Pitié Salpêtrière, Paris, France

    Dimitri Psimaras

  6. EBMT Paris Study Office, Paris, France

    Manuela Badoglio

  7. CHU de Poitiers, Poitiers, Université de Poitiers, Poitiers, France

    Mathieu Puyade

  8. MATHEC, Paris, France

    Mathieu Puyade, Dominique Farge & Zora Marjanovic

  9. Saint-Louis Hospital, Paris, France

    Dominique Farge

Authors
  1. Tamim Alsuliman
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  2. Dimitri Psimaras
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  3. Nicolas Stocker
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  4. Simona Sestili
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  7. Agnès Bonnin
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  8. Manuela Badoglio
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  10. Dominique Farge
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  11. Mohamad Mohty
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  12. Zora Marjanovic
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Contributions

TA: conceptualization, writing, drafting, bibliography, reviewing/editing. DF, ZM, MM: writing, drafting, reviewing/editing. MP, NS: drafting, reviewing/editing. ZVW, ABa, ABo, SS, DP, MB: reviewing/editing.

Corresponding author

Correspondence to Zora Marjanovic.

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Competing interests

TA reports lecture and/or consulting honoraria from Biotest and Amgen, all outside of the submitted work. Other authors do not declare any conflict of interest for this manuscript.

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Informed consent was obtained from the patient for the publication of this manuscript.

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Alsuliman, T., Psimaras, D., Stocker, N. et al. Autologous hematopoietic stem cell transplantation in a patient with multi-refractory stiff person syndrome. Bone Marrow Transplant 60, 86–88 (2025). https://doi.org/10.1038/s41409-024-02440-x

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