Frontiers in Immunology (Jul 2024)
Implications of disease-modifying therapies for multiple sclerosis on immune cells and response to COVID-19 vaccination
- Valeria Orrù,
- Valentina Serra,
- Michele Marongiu,
- Sandra Lai,
- Valeria Lodde,
- Magdalena Zoledziewska,
- Maristella Steri,
- Annalisa Loizedda,
- Monia Lobina,
- Maria Grazia Piras,
- Francesca Virdis,
- Giuseppe Delogu,
- Maria Giuseppina Marini,
- Maura Mingoia,
- Matteo Floris,
- Marco Masala,
- M. Paola Castelli,
- Rafaela Mostallino,
- Jessica Frau,
- Lorena Lorefice,
- Gabriele Farina,
- Marzia Fronza,
- Daniele Carmagnini,
- Elisa Carta,
- Silvy Pilotto,
- Silvy Pilotto,
- Paola Chessa,
- Paola Chessa,
- Marcella Devoto,
- Marcella Devoto,
- Paolo Castiglia,
- Paolo Solla,
- Paolo Solla,
- Roberto Ignazio Zarbo,
- Roberto Ignazio Zarbo,
- Maria Laura Idda,
- Maristella Pitzalis,
- Eleonora Cocco,
- Eleonora Cocco,
- Edoardo Fiorillo,
- Francesco Cucca,
- Francesco Cucca
Affiliations
- Valeria Orrù
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Valentina Serra
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Michele Marongiu
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Sandra Lai
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Valeria Lodde
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- Magdalena Zoledziewska
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Maristella Steri
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Annalisa Loizedda
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Monia Lobina
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Maria Grazia Piras
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Francesca Virdis
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Giuseppe Delogu
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- Maria Giuseppina Marini
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Maura Mingoia
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Matteo Floris
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- Marco Masala
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- M. Paola Castelli
- Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy
- Rafaela Mostallino
- Department of Biomedical Sciences, University of Cagliari, Monserrato, Italy
- Jessica Frau
- Regional Multiple Sclerosis Center, Azienda Sanitaria Locale (ASL) Cagliari, Cagliari, Italy
- Lorena Lorefice
- Regional Multiple Sclerosis Center, Azienda Sanitaria Locale (ASL) Cagliari, Cagliari, Italy
- Gabriele Farina
- Neurology Unit, Azienza Ospedaliera Universitaria (AOU) Sassari, Sassari, Italy
- Marzia Fronza
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Daniele Carmagnini
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Elisa Carta
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Silvy Pilotto
- Neurology Unit, Azienza Ospedaliera Universitaria (AOU) Sassari, Sassari, Italy
- Silvy Pilotto
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Paola Chessa
- Neurology Unit, Azienza Ospedaliera Universitaria (AOU) Sassari, Sassari, Italy
- Paola Chessa
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Marcella Devoto
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Marcella Devoto
- Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
- Paolo Castiglia
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
- Paolo Solla
- Neurology Unit, Azienza Ospedaliera Universitaria (AOU) Sassari, Sassari, Italy
- Paolo Solla
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
- Roberto Ignazio Zarbo
- Neurology Unit, Azienza Ospedaliera Universitaria (AOU) Sassari, Sassari, Italy
- Roberto Ignazio Zarbo
- Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy
- Maria Laura Idda
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- Maristella Pitzalis
- Institute for Genetic and Biomedical Research, National Research Council, Monserrato, Italy
- Eleonora Cocco
- Regional Multiple Sclerosis Center, Azienda Sanitaria Locale (ASL) Cagliari, Cagliari, Italy
- Eleonora Cocco
- Department of Medical Science and Public Health, University of Cagliari, Cagliari, Italy
- Edoardo Fiorillo
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Francesco Cucca
- Institute for Genetic and Biomedical Research, National Research Council, Lanusei, Italy
- Francesco Cucca
- Department of Biomedical Sciences, University of Sassari, Sassari, Italy
- DOI
- https://doi.org/10.3389/fimmu.2024.1416464
- Journal volume & issue
-
Vol. 15
Abstract
IntroductionDisease-modifying therapies (DMTs) have been shown to improve disease outcomes in multiple sclerosis (MS) patients. They may also impair the immune response to vaccines, including the SARS-CoV-2 vaccine. However, available data on both the intrinsic immune effects of DMTs and their influence on cellular response to the SARS-CoV-2 vaccine are still incomplete.MethodsHere, we evaluated the immune cell effects of 3 DMTs on the response to mRNA SARS-CoV-2 vaccination by comparing MS patients treated with one specific therapy (fingolimod, dimethyl fumarate, or natalizumab) with both healthy controls and untreated patients. We profiled 23 B-cell traits, 57 T-cell traits, and 10 cytokines, both at basal level and after stimulation with a pool of SARS-CoV-2 spike peptides, in 79 MS patients, treated with DMTs or untreated, and 32 healthy controls. Measurements were made before vaccination and at three time points after immunization.Results and DiscussionMS patients treated with fingolimod showed the strongest immune cell dysregulation characterized by a reduction in all measured lymphocyte cell classes; the patients also had increased immune cell activation at baseline, accompanied by reduced specific immune cell response to the SARS-CoV-2 vaccine. Also, anti-spike specific B cells progressively increased over the three time points after vaccination, even when antibodies measured from the same samples instead showed a decline. Our findings demonstrate that repeated booster vaccinations in MS patients are crucial to overcoming the immune cell impairment caused by DMTs and achieving an immune response to the SARS-CoV-2 vaccine comparable to that of healthy controls.
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