S1P receptor antagonists fingolimod and siponimod do not improve the outcome of experimental autoimmune myasthenia gravis mice after disease onset
| Autor: | Radharani Diallo, Siegfried Kohler, Falk Hiepe, Hanne Schaffert, Andreas Meisel, Andreas Pelz |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male T-Lymphocytes Immunology Plasma Cells Biology Neuromuscular junction 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Lymphopenia Benzyl Compounds medicine Immunology and Allergy Animals Humans Autoimmune disease Fingolimod Hydrochloride Multiple sclerosis Antibody titer Muscle weakness medicine.disease Fingolimod Myasthenia gravis Myasthenia Gravis Autoimmune Experimental Mice Inbred C57BL Receptors Lysosphingolipid 030104 developmental biology Siponimod medicine.anatomical_structure chemistry Antibody Formation Azetidines Cytokines Female medicine.symptom 030217 neurology & neurosurgery Immunosuppressive Agents medicine.drug |
| Zdroj: | European journal of immunology. 48(3) |
| ISSN: | 1521-4141 |
| Popis: | Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue in the presence of circulating antibodies against components of the neuromuscular junction. Most patients have a good prognosis, but some are refractory to standard-of-care immunosuppressive treatment and suffer from recurrent myasthenic crises. Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG. Here, we investigated whether fingolimod or siponimod improves outcome in EAMG mice when administered after disease onset, modeling the clinical setting in human MG. Both S1P antagonists inhibited lymphocyte egress, resulting in peripheral lymphopenia. After stimulation, there were differences in T-cell responses, but no change in either antibody titers or total or antigen-specific plasma cell populations after treatment. Most importantly, disease incidence and severity were not influenced by fingolimod or siponimod therapy. Although fingolimod and siponimod did lead to subtle changes in T-cell responses, they had no significant effect on antibody titers and disease severity. In conclusion, our data show no evidence of a therapeutic potential for S1P receptor antagonists in MG treatment. |
| Databáze: | OpenAIRE |
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