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PET-measurable innate immune cell activation reduction in chronic active lesions in PPMS brain after rituximab treatment: a case report

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Abstract

Objectives

To evaluate the effects of rituximab treatment on innate immune cell activation in primary progressive multiple sclerosis (PPMS).

Methods

A 48-year-old woman with PPMS was started on rituximab shortly after diagnosis. [11C]PK11195 PET imaging was employed to assess innate immune cell activation with special interest in the white matter around chronic lesions. PET, MRI, and disability measurements were performed at baseline and after 18 months of rituximab treatment. Specific binding of [11C]PK11195 was quantified using mean distribution volume ratios (DVRs), and at voxel-level based on proportions of active voxels.

Results

The PPMS patient had higher PK11195 DVRs and higher proportions of active voxels in the thalamus and the normal appearing white matter compared to the healthy control group. The thalamic and perilesional white matter DVRs and the proportions of active voxels decreased after rituximab treatment. The patient remained clinically stable during the 5-years follow-up.

Conclusions

This case suggests that while a degree of smoldering activity persists, high efficacy B-cell-targeting therapy may contribute to reduced innate immune cell activation in PPMS brain areas relevant for disease progression. This case supports the therapeutic concept that controlling smoldering brain inflammation is beneficial for slowing down progression independent of relapses.

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Data availability

Any anonymized data used in the preparation of this article will be made available by request of a qualified investigator.

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Funding

Professor Laura Airas is supported by Finnish Academy and the Juselius Foundation. Dr. Sucksdorff has received research support from The Finnish Medical Foundation, The Finnish MS Foundation, and The Finnish Medical Society (Finska Läkaresällskapet). Dr. Lehto and Dr. Matilainen are financially supported by the InFLAMES Flagship Programme of the Academy of Finland (decision number: 337530).

Author information

Authors and Affiliations

  1. Turku PET Centre, Turku University Hospital, Po Box 52, 20521, Turku, Finland

    Jussi Lehto, Marcus Sucksdorff, Marjo Nylund, Roope Raitanen & Markus Matilainen

  2. Clinical Neurosciences, University of Turku, Turku, Finland

    Marcus Sucksdorff, Marjo Nylund, Roope Raitanen & Laura Airas

  3. Neurocenter, Turku University Hospital, Turku, Finland

    Jussi Lehto, Marcus Sucksdorff & Laura Airas

  4. Faculty of Science and Engineering, Åbo Akademi University, Turku, Finland

    Markus Matilainen

Authors
  1. Jussi Lehto
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  2. Marcus Sucksdorff
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  3. Marjo Nylund
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  4. Roope Raitanen
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  5. Markus Matilainen
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  6. Laura Airas
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Corresponding author

Correspondence to Jussi Lehto.

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Conflicts of interest

Dr. Airas has obtained institutional research support from Novartis, Sanofi-Genzyme, and Merck and compensation for lectures and advising from Novartis, Sanofi, Merck, Roche, and Janssen.

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Cite this article

Lehto, J., Sucksdorff, M., Nylund, M. et al. PET-measurable innate immune cell activation reduction in chronic active lesions in PPMS brain after rituximab treatment: a case report. J Neurol 270, 2329–2332 (2023). https://doi.org/10.1007/s00415-022-11539-4

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  • DOI: https://doi.org/10.1007/s00415-022-11539-4

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