The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy
Considering their potent immunomodulatory properties, therapeutic applications of <i>Trichuris suis</i> ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical...
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MDPI AG
2021-01-01
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| Online Access: | https://www.mdpi.com/2075-1729/11/2/101 |
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| author | Ivet A. Yordanova Friederike Ebner Axel Ronald Schulz Svenja Steinfelder Berit Rosche Anna Bolze Friedemann Paul Henrik E. Mei Susanne Hartmann |
| author_facet | Ivet A. Yordanova Friederike Ebner Axel Ronald Schulz Svenja Steinfelder Berit Rosche Anna Bolze Friedemann Paul Henrik E. Mei Susanne Hartmann |
| author_sort | Ivet A. Yordanova |
| collection | DOAJ |
| description | Considering their potent immunomodulatory properties, therapeutic applications of <i>Trichuris suis</i> ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical phase 1 and 2 studies have demonstrated TSO treatment to be safe and well tolerated in MS patients, however, they reported only modest clinical efficacy. We therefore addressed the cellular and humoral immune responses directed against parasite antigens in individual MS patients receiving controlled TSO treatment (2500 TSO p.o. every 2 weeks for 12 month). Peripheral blood mononuclear cells (PBMC) of MS patients treated with TSO (<i>n</i> = 5) or placebo (<i>n</i> = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for <i>T. suis</i> excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DR<sup>high</sup> plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4<sup>+</sup> and CD8<sup>+</sup> T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR<sup>+</sup>CD4<sup>+</sup> T cells in TSO-treated patients only. Frequencies of Gata3<sup>+</sup> Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3<sup>+</sup> Treg frequencies varied greatly between individuals. Using a <i>T. suis</i> antigen-specific T cell expansion assay, we also detected patient-to-patient variation of antigen-specific T cell recall responses and cytokine production. In summary, MS patients receiving TSO treatment established a <i>T. suis</i>-specific T- and B-cell response, however, with varying degrees of T cell responses and cellular functionality across individuals, which might account for the overall miscellaneous clinical efficacy in the studied patients. |
| first_indexed | 2024-03-09T03:17:44Z |
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| issn | 2075-1729 |
| language | English |
| last_indexed | 2024-03-09T03:17:44Z |
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| spelling | doaj.art-3595f6a288e342869d474fc0305a149f2023-12-03T15:15:30ZengMDPI AGLife2075-17292021-01-0111210110.3390/life11020101The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova ImmunotherapyIvet A. Yordanova0Friederike Ebner1Axel Ronald Schulz2Svenja Steinfelder3Berit Rosche4Anna Bolze5Friedemann Paul6Henrik E. Mei7Susanne Hartmann8Institute of Immunology, Center for Infection Medicine, Freie Universität Berlin, D-14163 Berlin, GermanyInstitute of Immunology, Center for Infection Medicine, Freie Universität Berlin, D-14163 Berlin, GermanyGerman Rheumatism Research Center Berlin (DRFZ), a Leibniz Institute, D-10117 Berlin, GermanyMax Delbrück Center for Molecular Medicine, D-13125 Berlin, GermanyDepartment of Neurology and Experimental Neurology, Charité—Universitätsmedizin Berlin, D-10117 Berlin, GermanyNeuroCure Clinical Research Center, Charité—Universitätsmedizin Berlin, D-10117 Berlin, GermanyClinical and Experimental Multiple Sclerosis Research Center, Charité—Universitätsmedizin Berlin, D-10117 Berlin, GermanyGerman Rheumatism Research Center Berlin (DRFZ), a Leibniz Institute, D-10117 Berlin, GermanyInstitute of Immunology, Center for Infection Medicine, Freie Universität Berlin, D-14163 Berlin, GermanyConsidering their potent immunomodulatory properties, therapeutic applications of <i>Trichuris suis</i> ova (TSO) are studied as potential alternative treatment of autoimmune disorders like multiple sclerosis (MS), rheumatoid arthritis (RA), or inflammatory bowel disease (IBD). Clinical phase 1 and 2 studies have demonstrated TSO treatment to be safe and well tolerated in MS patients, however, they reported only modest clinical efficacy. We therefore addressed the cellular and humoral immune responses directed against parasite antigens in individual MS patients receiving controlled TSO treatment (2500 TSO p.o. every 2 weeks for 12 month). Peripheral blood mononuclear cells (PBMC) of MS patients treated with TSO (<i>n</i> = 5) or placebo (<i>n</i> = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for <i>T. suis</i> excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DR<sup>high</sup> plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4<sup>+</sup> and CD8<sup>+</sup> T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR<sup>+</sup>CD4<sup>+</sup> T cells in TSO-treated patients only. Frequencies of Gata3<sup>+</sup> Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3<sup>+</sup> Treg frequencies varied greatly between individuals. Using a <i>T. suis</i> antigen-specific T cell expansion assay, we also detected patient-to-patient variation of antigen-specific T cell recall responses and cytokine production. In summary, MS patients receiving TSO treatment established a <i>T. suis</i>-specific T- and B-cell response, however, with varying degrees of T cell responses and cellular functionality across individuals, which might account for the overall miscellaneous clinical efficacy in the studied patients.https://www.mdpi.com/2075-1729/11/2/101<i>Trichuris suis</i>TSOhelminth therapymultiple sclerosismass cytometryclinical trial |
| spellingShingle | Ivet A. Yordanova Friederike Ebner Axel Ronald Schulz Svenja Steinfelder Berit Rosche Anna Bolze Friedemann Paul Henrik E. Mei Susanne Hartmann The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy Life <i>Trichuris suis</i> TSO helminth therapy multiple sclerosis mass cytometry clinical trial |
| title | The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy |
| title_full | The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy |
| title_fullStr | The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy |
| title_full_unstemmed | The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy |
| title_short | The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled <i>Trichuris suis</i> Ova Immunotherapy |
| title_sort | worm specific immune response in multiple sclerosis patients receiving controlled i trichuris suis i ova immunotherapy |
| topic | <i>Trichuris suis</i> TSO helminth therapy multiple sclerosis mass cytometry clinical trial |
| url | https://www.mdpi.com/2075-1729/11/2/101 |
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