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Effects of Teriflunomide on B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis.
Immunol Invest. 2020 Jun 29 [Online ahead of print]II

Abstract

Antigen-specific immune responses are crucially involved in both multiple sclerosis (MS) and myasthenia gravis (MG). Teriflunomide is an immunomodulatory agent approved for treatment of MS through inhibition of lymphocyte proliferation. MG associated with muscle-specific tyrosine kinase (MuSK) antibodies often manifests with a severe disease course, prompting development of effective treatment methods. To evaluate whether teriflunomide treatment may ameliorate MuSK-autoimmunity, experimental autoimmune MG (EAMG) was induced by immunizing C57BL/6 (B6) mice three times with MuSK in complete Freund's adjuvant (CFA) (n = 17). MuSK-immunized mice were treated daily with teriflunomide (n = 8) or PBS (n = 9) starting from the third immunization (week 8) to termination (week 14). Clinical severity of EAMG was monitored. Immunological alterations were evaluated by measurement of anti-MuSK IgG, neuromuscular junction deposits, and flow cytometric analysis of lymph node cells. In MS patients under teriflunomide treatment, the peripheral blood B cell subset profile was analyzed. B6 mice treated with teriflunomide displayed relatively preserved body weight, lower EAMG prevalence, reduced average clinical grades, higher inverted screen scores, diminished anti-MuSK antibody and NMJ deposit levels. Amelioration of EAMG findings was associated with reduced memory B cell ratios in the lymph nodes. Similarly, MS patients under teriflunomide treatment showed reduced memory B cell, plasma cell, and plasmablast ratios. Teriflunomide treatment has effectively ameliorated MuSK-autoimmunity and thus may putatively be used in long-term management of MuSK-MG as an auxiliary treatment method. Teriflunomide appears to exert beneficial effects through inhibition of effector B cells.

Authors+Show Affiliations

Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey.Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey.Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey. Sophie Davis Biomedical Education Program, CUNY School of Medicine , New York, NY, USA.Department of Neurology, Haydarpasa Numune Education and Research Hospital , Istanbul, Turkey.Department of Neurology, Istanbul Medical Faculty, Istanbul University , Istanbul, Turkey.First Department of Neurology, Eginition Hospital, Medical School, National and Kapodistrian University of Athens , Athens, Greece. Tzartos NeuroDiagnostics , Athens, Greece.Department of Immunology, Hellenic Pasteur Institute , Athens, Greece.Department of Neuroscience, Aziz Sancar Institute of Experimental Medicine, Istanbul University , Istanbul, Turkey.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32597289

Citation

Yilmaz, Vuslat, et al. "Effects of Teriflunomide On B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis." Immunological Investigations, 2020, pp. 1-14.
Yilmaz V, Ulusoy C, Hajtovic S, et al. Effects of Teriflunomide on B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis. Immunol Invest. 2020.
Yilmaz, V., Ulusoy, C., Hajtovic, S., Turkoglu, R., Kurtuncu, M., Tzartos, J., Lazaridis, K., & Tuzun, E. (2020). Effects of Teriflunomide on B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis. Immunological Investigations, 1-14. https://doi.org/10.1080/08820139.2020.1785491
Yilmaz V, et al. Effects of Teriflunomide On B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis. Immunol Invest. 2020 Jun 29;1-14. PubMed PMID: 32597289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of Teriflunomide on B Cell Subsets in MuSK-Induced Experimental Autoimmune Myasthenia Gravis and Multiple Sclerosis. AU - Yilmaz,Vuslat, AU - Ulusoy,Canan, AU - Hajtovic,Sabastian, AU - Turkoglu,Recai, AU - Kurtuncu,Murat, AU - Tzartos,John, AU - Lazaridis,Konstantinos, AU - Tuzun,Erdem, Y1 - 2020/06/29/ PY - 2020/7/1/pubmed PY - 2020/7/1/medline PY - 2020/6/30/entrez KW - Myasthenia gravis KW - autoimmunity KW - memory cells KW - muscle-specific kinase KW - teriflunomide SP - 1 EP - 14 JF - Immunological investigations JO - Immunol. Invest. N2 - Antigen-specific immune responses are crucially involved in both multiple sclerosis (MS) and myasthenia gravis (MG). Teriflunomide is an immunomodulatory agent approved for treatment of MS through inhibition of lymphocyte proliferation. MG associated with muscle-specific tyrosine kinase (MuSK) antibodies often manifests with a severe disease course, prompting development of effective treatment methods. To evaluate whether teriflunomide treatment may ameliorate MuSK-autoimmunity, experimental autoimmune MG (EAMG) was induced by immunizing C57BL/6 (B6) mice three times with MuSK in complete Freund's adjuvant (CFA) (n = 17). MuSK-immunized mice were treated daily with teriflunomide (n = 8) or PBS (n = 9) starting from the third immunization (week 8) to termination (week 14). Clinical severity of EAMG was monitored. Immunological alterations were evaluated by measurement of anti-MuSK IgG, neuromuscular junction deposits, and flow cytometric analysis of lymph node cells. In MS patients under teriflunomide treatment, the peripheral blood B cell subset profile was analyzed. B6 mice treated with teriflunomide displayed relatively preserved body weight, lower EAMG prevalence, reduced average clinical grades, higher inverted screen scores, diminished anti-MuSK antibody and NMJ deposit levels. Amelioration of EAMG findings was associated with reduced memory B cell ratios in the lymph nodes. Similarly, MS patients under teriflunomide treatment showed reduced memory B cell, plasma cell, and plasmablast ratios. Teriflunomide treatment has effectively ameliorated MuSK-autoimmunity and thus may putatively be used in long-term management of MuSK-MG as an auxiliary treatment method. Teriflunomide appears to exert beneficial effects through inhibition of effector B cells. SN - 1532-4311 UR - https://www.unboundmedicine.com/medline/citation/32597289/Effects_of_Teriflunomide_on_B_Cell_Subsets_in_MuSK-Induced_Experimental_Autoimmune_Myasthenia_Gravis_and_Multiple_Sclerosis L2 - http://www.tandfonline.com/doi/full/10.1080/08820139.2020.1785491 DB - PRIME DP - Unbound Medicine ER -
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