Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis
Abstract Background The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Journal of Neuroinflammation |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12974-022-02635-3 |
| _version_ | 1828296970518659072 |
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| author | Celia Camacho-Toledano Isabel Machín-Díaz Leticia Calahorra María Cabañas-Cotillas David Otaegui Tamara Castillo-Triviño Luisa María Villar Lucienne Costa-Frossard Manuel Comabella Luciana Midaglia José Manuel García-Domínguez Jennifer García-Arocha María Cristina Ortega Diego Clemente |
| author_facet | Celia Camacho-Toledano Isabel Machín-Díaz Leticia Calahorra María Cabañas-Cotillas David Otaegui Tamara Castillo-Triviño Luisa María Villar Lucienne Costa-Frossard Manuel Comabella Luciana Midaglia José Manuel García-Domínguez Jennifer García-Arocha María Cristina Ortega Diego Clemente |
| author_sort | Celia Camacho-Toledano |
| collection | DOAJ |
| description | Abstract Background The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients. Methods Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients’ peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed. Results Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment. Conclusion Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod. |
| first_indexed | 2024-04-13T12:20:05Z |
| format | Article |
| id | doaj.art-0f9c418f15814c33962ee4b700889141 |
| institution | Directory Open Access Journal |
| issn | 1742-2094 |
| language | English |
| last_indexed | 2024-04-13T12:20:05Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Neuroinflammation |
| spelling | doaj.art-0f9c418f15814c33962ee4b7008891412022-12-22T02:47:15ZengBMCJournal of Neuroinflammation1742-20942022-11-0119112210.1186/s12974-022-02635-3Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosisCelia Camacho-Toledano0Isabel Machín-Díaz1Leticia Calahorra2María Cabañas-Cotillas3David Otaegui4Tamara Castillo-Triviño5Luisa María Villar6Lucienne Costa-Frossard7Manuel Comabella8Luciana Midaglia9José Manuel García-Domínguez10Jennifer García-Arocha11María Cristina Ortega12Diego Clemente13Neuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMMultiple Sclerosis Unit, Biodonostia Health InstituteMultiple Sclerosis Unit, Biodonostia Health InstituteImmunology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Immunology Department, Hospital Universitario Ramón y Cajal, Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS)Neurology-Neuroimmunology Service, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron, Hospital Universitari Vall d’Hebron, Universitat Autònoma de BarcelonaNeurology-Neuroimmunology Service, Centre d’Esclerosi Múltiple de Catalunya (Cemcat), Institut de Recerca Vall d’Hebron, Hospital Universitari Vall d’Hebron, Universitat Autònoma de BarcelonaMultiple Sclerosis Unit, Department of Neurology, Hospital General Universitario Gregorio MarañónNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMNeuroimmuno-Repair Group, Hospital Nacional de Parapléjicos-SESCAMAbstract Background The increasing number of treatments that are now available to manage patients with multiple sclerosis (MS) highlights the need to develop biomarkers that can be used within the framework of individualized medicine. Fingolimod is a disease-modifying treatment that belongs to the sphingosine-1-phosphate receptor modulators. In addition to inhibiting T cell egress from lymph nodes, fingolimod promotes the immunosuppressive activity of myeloid-derived suppressor cells (MDSCs), whose monocytic subset (M-MDSCs) can be used as a biomarker of disease severity, as well as the degree of demyelination and extent of axonal damage in the experimental autoimmune encephalomyelitis (EAE) model of MS. In the present study, we have assessed whether the abundance of circulating M-MDSCs may represent a useful biomarker of fingolimod efficacy in EAE and in the clinical context of MS patients. Methods Treatment with vehicle or fingolimod was orally administered to EAE mice for 14 days in an individualized manner, starting the day when each mouse began to develop clinical signs. Peripheral blood from EAE mice was collected previous to treatment and human peripheral blood mononuclear cells (PBMCs) were collected from fingolimod to treat MS patients’ peripheral blood. In both cases, M-MDSCs abundance was analyzed by flow cytometry and its relationship with the future clinical affectation of each individual animal or patient was assessed. Results Fingolimod-treated animals presented a milder EAE course with less demyelination and axonal damage, although a few animals did not respond well to treatment and they invariably had fewer M-MDSCs prior to initiating the treatment. Remarkably, M-MDSC abundance was also found to be an important and specific parameter to distinguish EAE mice prone to better fingolimod efficacy. Finally, in a translational effort, M-MDSCs were quantified in MS patients at baseline and correlated with different clinical parameters after 12 months of fingolimod treatment. M-MDSCs at baseline were highly representative of a good therapeutic response to fingolimod, i.e., patients who met at least two of the criteria used to define non-evidence of disease activity-3 (NEDA-3) 12 months after treatment. Conclusion Our data indicate that M-MDSCs might be a useful predictive biomarker of the response of MS patients to fingolimod.https://doi.org/10.1186/s12974-022-02635-3EAEMDSCsS1PRResponder and non-responderPersonalized medicine |
| spellingShingle | Celia Camacho-Toledano Isabel Machín-Díaz Leticia Calahorra María Cabañas-Cotillas David Otaegui Tamara Castillo-Triviño Luisa María Villar Lucienne Costa-Frossard Manuel Comabella Luciana Midaglia José Manuel García-Domínguez Jennifer García-Arocha María Cristina Ortega Diego Clemente Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis Journal of Neuroinflammation EAE MDSCs S1PR Responder and non-responder Personalized medicine |
| title | Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| title_full | Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| title_fullStr | Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| title_full_unstemmed | Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| title_short | Peripheral myeloid-derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| title_sort | peripheral myeloid derived suppressor cells are good biomarkers of the efficacy of fingolimod in multiple sclerosis |
| topic | EAE MDSCs S1PR Responder and non-responder Personalized medicine |
| url | https://doi.org/10.1186/s12974-022-02635-3 |
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