Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators
BackgroundHigh-dose glucocorticoids are the standard treatment for acute relapses in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Therapeutic apheresis can be considered for the escalation of relapse therapy, but some patients still do not recover sufficie...
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Frontiers Media S.A.
2025-01-01
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| Series: | Frontiers in Immunology |
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| author | Michael Hecker Brit Fitzner Isis Ludwig-Portugall Friederike Bohne Edmar Heyland Juliane Klehmet Matthias Grothe Matthias Schwab Alexander Winkelmann Stefanie Meister Ales Dudesek Hannah Wurm Ilya Ayzenberg Ingo Kleiter Ingo Kleiter Corinna Trebst Martin W. Hümmert Bernhard Neumann Bernhard Neumann Klaus Eulitz Dirk Koczan Uwe K. Zettl |
| author_facet | Michael Hecker Brit Fitzner Isis Ludwig-Portugall Friederike Bohne Edmar Heyland Juliane Klehmet Matthias Grothe Matthias Schwab Alexander Winkelmann Stefanie Meister Ales Dudesek Hannah Wurm Ilya Ayzenberg Ingo Kleiter Ingo Kleiter Corinna Trebst Martin W. Hümmert Bernhard Neumann Bernhard Neumann Klaus Eulitz Dirk Koczan Uwe K. Zettl |
| author_sort | Michael Hecker |
| collection | DOAJ |
| description | BackgroundHigh-dose glucocorticoids are the standard treatment for acute relapses in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Therapeutic apheresis can be considered for the escalation of relapse therapy, but some patients still do not recover sufficiently. We aimed to explore the effects of apheresis on humoral and cellular immune parameters and to identify features that correlate with beneficial clinical outcomes.MethodsWe studied two cohorts comprising a total of 63 patients with MS or NMOSD who were undergoing relapse therapy with either methylprednisolone or apheresis. Blood samples were collected immediately before and after therapy to isolate plasma or serum as well as immune cells. We then measured (1) concentrations of the immunoglobulin isotypes IgG, IgM and IgA, (2) antibody reactivities against 12 peptides derived from potential autoantigens and Epstein-Barr virus proteins, (3) frequencies of CD19+ B cells, CD3+ T cells and CD14+ monocytes, (4) transcriptome profiles of CD19+ B cells and CD4+ T cells and (5) mRNA levels of 7 cytotoxicity-related genes in CD4+ T cells. The data were compared with regard to changes under therapy and with regard to differences between clinical responders and non-responders.ResultsThe initial therapy with methylprednisolone had no significant effect on immunoglobulin levels and (auto)antibody reactivities (nmax=27 MS patients). In contrast, MS patients who underwent apheresis (nmax=27) showed strong immunoglobulin reduction rates, especially for IgG, and decreased antibody reactivities against all tested peptides. EBNA1 (amino acids 391-410) was the only peptide that also reached the significance level in NMOSD patients (n=9). Non-responders to apheresis (n=12) had on average higher anti-EBNA1 (391-410) reactivities than responders (n=24) at baseline. Apheresis also led to a decrease in the proportion of monocytes, an increase in the proportion of T cells (n=29 patients with MS or NMOSD) and moderate transcriptome changes (nmax=4 MS patients). A gene expression signature that is characteristic of CD4+ cytotoxic T lymphocytes (CD4-CTLs) was found to be elevated at baseline in non-responders to apheresis, although this could not be validated with statistical significance (n=19 MS patients).ConclusionOur data reveal that therapeutic apheresis in MS rapidly leads to a significant decrease in IgG reactivities against EBNA1 (391-410) and cross-reactive targets such as GlialCAM (370-389) and also has an impact on the gene expression of B cells and T cells. Further studies are required to verify whether anti-EBNA1 (391-410) antibody reactivities and the expression of CD4-CTL-related genes may be indicative of the individual clinical response to this therapy. |
| format | Article |
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| institution | Kabale University |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-be579a60752843e68003a335c7099c582025-01-30T05:10:19ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-01-011610.3389/fimmu.2025.15314471531447Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicatorsMichael Hecker0Brit Fitzner1Isis Ludwig-Portugall2Friederike Bohne3Edmar Heyland4Juliane Klehmet5Matthias Grothe6Matthias Schwab7Alexander Winkelmann8Stefanie Meister9Ales Dudesek10Hannah Wurm11Ilya Ayzenberg12Ingo Kleiter13Ingo Kleiter14Corinna Trebst15Martin W. Hümmert16Bernhard Neumann17Bernhard Neumann18Klaus Eulitz19Dirk Koczan20Uwe K. Zettl21Division of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyDivision of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyR&D Apheresis, Miltenyi Biotec B.V. & Co. KG, Teterow, GermanyR&D Apheresis, Miltenyi Biotec B.V. & Co. KG, Teterow, GermanyR&D Apheresis, Miltenyi Biotec B.V. & Co. KG, Teterow, GermanyCenter for Multiple Sclerosis, Department of Neurology, Jüdisches Krankenhaus Berlin, Berlin, GermanyDepartment of Neurology, University Medicine Greifswald, Greifswald, GermanyDepartment of Neurology, Jena University Hospital, Jena, GermanyDivision of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyDivision of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyDivision of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyDepartment of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, GermanyDepartment of Neurology, St. Josef-Hospital, Ruhr University Bochum, Bochum, GermanyMarianne-Strauß-Klinik, Behandlungszentrum Kempfenhausen für Multiple Sklerose Kranke gGmbH, Berg, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, Hannover Medical School, Hannover, GermanyDepartment of Neurology, University of Regensburg, Bezirksklinikum, Regensburg, Germany0Department of Neurology, Donau-Isar-Klinikum Deggendorf, Deggendorf, GermanyR&D Apheresis, Miltenyi Biotec B.V. & Co. KG, Teterow, Germany1Institute of Immunology, Rostock University Medical Center, Rostock, GermanyDivision of Neuroimmunology, Department of Neurology, Rostock University Medical Center, Rostock, GermanyBackgroundHigh-dose glucocorticoids are the standard treatment for acute relapses in patients with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD). Therapeutic apheresis can be considered for the escalation of relapse therapy, but some patients still do not recover sufficiently. We aimed to explore the effects of apheresis on humoral and cellular immune parameters and to identify features that correlate with beneficial clinical outcomes.MethodsWe studied two cohorts comprising a total of 63 patients with MS or NMOSD who were undergoing relapse therapy with either methylprednisolone or apheresis. Blood samples were collected immediately before and after therapy to isolate plasma or serum as well as immune cells. We then measured (1) concentrations of the immunoglobulin isotypes IgG, IgM and IgA, (2) antibody reactivities against 12 peptides derived from potential autoantigens and Epstein-Barr virus proteins, (3) frequencies of CD19+ B cells, CD3+ T cells and CD14+ monocytes, (4) transcriptome profiles of CD19+ B cells and CD4+ T cells and (5) mRNA levels of 7 cytotoxicity-related genes in CD4+ T cells. The data were compared with regard to changes under therapy and with regard to differences between clinical responders and non-responders.ResultsThe initial therapy with methylprednisolone had no significant effect on immunoglobulin levels and (auto)antibody reactivities (nmax=27 MS patients). In contrast, MS patients who underwent apheresis (nmax=27) showed strong immunoglobulin reduction rates, especially for IgG, and decreased antibody reactivities against all tested peptides. EBNA1 (amino acids 391-410) was the only peptide that also reached the significance level in NMOSD patients (n=9). Non-responders to apheresis (n=12) had on average higher anti-EBNA1 (391-410) reactivities than responders (n=24) at baseline. Apheresis also led to a decrease in the proportion of monocytes, an increase in the proportion of T cells (n=29 patients with MS or NMOSD) and moderate transcriptome changes (nmax=4 MS patients). A gene expression signature that is characteristic of CD4+ cytotoxic T lymphocytes (CD4-CTLs) was found to be elevated at baseline in non-responders to apheresis, although this could not be validated with statistical significance (n=19 MS patients).ConclusionOur data reveal that therapeutic apheresis in MS rapidly leads to a significant decrease in IgG reactivities against EBNA1 (391-410) and cross-reactive targets such as GlialCAM (370-389) and also has an impact on the gene expression of B cells and T cells. Further studies are required to verify whether anti-EBNA1 (391-410) antibody reactivities and the expression of CD4-CTL-related genes may be indicative of the individual clinical response to this therapy.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531447/fullmultiple sclerosisneuromyelitis optica spectrum disorderacute relapseapheresisglucocorticoidsantibodies |
| spellingShingle | Michael Hecker Brit Fitzner Isis Ludwig-Portugall Friederike Bohne Edmar Heyland Juliane Klehmet Matthias Grothe Matthias Schwab Alexander Winkelmann Stefanie Meister Ales Dudesek Hannah Wurm Ilya Ayzenberg Ingo Kleiter Ingo Kleiter Corinna Trebst Martin W. Hümmert Bernhard Neumann Bernhard Neumann Klaus Eulitz Dirk Koczan Uwe K. Zettl Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators Frontiers in Immunology multiple sclerosis neuromyelitis optica spectrum disorder acute relapse apheresis glucocorticoids antibodies |
| title | Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators |
| title_full | Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators |
| title_fullStr | Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators |
| title_full_unstemmed | Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators |
| title_short | Apheresis for the treatment of relapses in MS and NMOSD: reduced antibody reactivities, gene expression changes and potential clinical response indicators |
| title_sort | apheresis for the treatment of relapses in ms and nmosd reduced antibody reactivities gene expression changes and potential clinical response indicators |
| topic | multiple sclerosis neuromyelitis optica spectrum disorder acute relapse apheresis glucocorticoids antibodies |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1531447/full |
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