Neuropediatrics 2023; 54(S 01): S1-S32
DOI: 10.1055/s-0043-1777151
Neuroimmunologie

Study of the Lymphocyte Profile in Highly Active Pediatric Multiple Sclerosis Patients before and after Therapy with Fingolimod

G. Koukou
1   Clinic for Neuropediatrics, Children's Hospital Datteln, University Witten-Herdecke, Datteln, Deutschland
2   Department of Human Medicine, Faculty of Health, University Witten/Herdecke, Chair for Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten, Deutschland
,
A. Karydi
1   Clinic for Neuropediatrics, Children's Hospital Datteln, University Witten-Herdecke, Datteln, Deutschland
,
S. Mader
3   Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-Universität München, München, Deutschland
,
S. Winklmeier
3   Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-Universität München, München, Deutschland
,
A. Bertolini
1   Clinic for Neuropediatrics, Children's Hospital Datteln, University Witten-Herdecke, Datteln, Deutschland
,
C. Hagedorn
2   Department of Human Medicine, Faculty of Health, University Witten/Herdecke, Chair for Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten, Deutschland
,
E. Meinl
3   Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-Universität München, München, Deutschland
,
F. Kreppel
2   Department of Human Medicine, Faculty of Health, University Witten/Herdecke, Chair for Biochemistry and Molecular Medicine, Center for Biomedical Education and Research (ZBAF), Witten, Deutschland
,
K. Rostásy
1   Clinic for Neuropediatrics, Children's Hospital Datteln, University Witten-Herdecke, Datteln, Deutschland
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    Background: Fingolimod has proven to be very effective in regard to relapse reduction and radiological progression in pediatric MS (pedMS). Until now, the effects of fingolimod in children on the different lymphocyte subsets have not yet been studied. Here, we characterized the phenotype of T cell subsets (naive, T-effector memory, T-central memory, TEMRA, Th17, Th17.1) and determined the serum neurofilament light chain (sNfL) in pedMS patients before and after therapy.

    Methods: Peripheral blood mononuclear cells were obtained from pedMS and healthy individuals and analyzed for surface markers with flow cytometry. Statistical analysis was performed with one-way ANOVA and Holm-Sidak for multiple comparison test.

    Results: Nine patients were recruited. After treatment, all developed a lymphopenia and prominent reduction in the CD4+ in contrast to the relatively elevated CD8+ compartment (p = 0.0041, p = 0.024). Further analysis revealed a reduction of naive CD4+ and CD8+ (p = 0.041, p = 0.00026). CD4+ T-effector memory cells (TEM) were significantly increased (p = 0.0025). CD8+ TEM cells were increased but not statistically significant. CD4+ and CD8+ T-central memory (TCM) cells moderately decreased and TEMRA increased. Interestingly, Th17 lymphocytes were unaffected after therapy. Moreover, two groups of patients were observed, either with elevated or decreased Th17.1 cells.

    Conclusion: Fingolimod treatment successfully led to a reduction of naive and TCM with retention of TEM cells thereby limiting the circulation of autoreactive T-cells which derive from TCM. Surprisingly, reduced Th17.1 cells, which associate with disease activity, were detected only in a group of patients. Comparisons of the results with clinical characteristics such as relapses, lesion burden, and sNfL levels are currently being analyzed.


     

    No conflict of interest has been declared by the author(s).

    Publication History

    Article published online:
    13 November 2023

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