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Article

The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy

1
Institute of Immunology, Center for Infection Medicine, Freie Universität Berlin, D-14163 Berlin, Germany
2
German Rheumatism Research Center Berlin (DRFZ), a Leibniz Institute, D-10117 Berlin, Germany
3
Max Delbrück Center for Molecular Medicine, D-13125 Berlin, Germany
4
Department of Neurology and Experimental Neurology, Charité—Universitätsmedizin Berlin, D-10117 Berlin, Germany
5
Clinical and Experimental Multiple Sclerosis Research Center, Charité—Universitätsmedizin Berlin, D-10117 Berlin, Germany
6
NeuroCure Clinical Research Center, Charité—Universitätsmedizin Berlin, D-10117 Berlin, Germany
7
Experimental and Clinical Research Center, Max Delbrück Center for Molecular Medicine, Charité—Universitätsmedizin Berlin, D-10117 Berlin, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Cristina Cutillas
Life 2021, 11(2), 101; https://doi.org/10.3390/life11020101
Received: 15 December 2020 / Revised: 19 January 2021 / Accepted: 25 January 2021 / Published: 29 January 2021
(This article belongs to the Special Issue Trichuris: Other World, Other Life)
Considering their potent immunomodulatory properties, therapeutic applications of Trichuris suis 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 (n = 5) or placebo (n = 6) were analyzed. A continuous increase of serum IgG and IgE antibodies specific for T. suis excretory/secretory antigens was observed up to 12 months post-treatment. This was consistent with mass cytometry analysis identifying an increase of activated HLA-DRhigh plasmablast frequencies in TSO-treated patients. While stable and comparable frequencies of total CD4+ and CD8+ T cells were detected in placebo and TSO-treated patients over time, we observed an increase of activated HLA-DR+CD4+ T cells in TSO-treated patients only. Frequencies of Gata3+ Th2 cells and Th1/Th2 ratios remained stable during TSO treatment, while Foxp3+ Treg frequencies varied greatly between individuals. Using a T. suis 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 T. suis-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. View Full-Text
Keywords: Trichuris suis; TSO; helminth therapy; multiple sclerosis; mass cytometry; clinical trial Trichuris suis; TSO; helminth therapy; multiple sclerosis; mass cytometry; clinical trial
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MDPI and ACS Style

Yordanova, I.A.; Ebner, F.; Schulz, A.R.; Steinfelder, S.; Rosche, B.; Bolze, A.; Paul, F.; Mei, H.E.; Hartmann, S. The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy. Life 2021, 11, 101. https://doi.org/10.3390/life11020101

AMA Style

Yordanova IA, Ebner F, Schulz AR, Steinfelder S, Rosche B, Bolze A, Paul F, Mei HE, Hartmann S. The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy. Life. 2021; 11(2):101. https://doi.org/10.3390/life11020101

Chicago/Turabian Style

Yordanova, Ivet A., Friederike Ebner, Axel R. Schulz, Svenja Steinfelder, Berit Rosche, Anna Bolze, Friedemann Paul, Henrik E. Mei, and Susanne Hartmann. 2021. "The Worm-Specific Immune Response in Multiple Sclerosis Patients Receiving Controlled Trichuris suis Ova Immunotherapy" Life 11, no. 2: 101. https://doi.org/10.3390/life11020101

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