CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis
Abstract Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), with a largely unknown etiology, where mitochondrial dysfunction likely contributes to neuroaxonal loss and brain atrophy. Mirroring the CNS, peripheral immune cells from patients with...
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Nature Portfolio
2024-03-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-57592-z |
| _version_ | 1827301127870218240 |
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| author | Filipe Cortes-Figueiredo Susanna Asseyer Claudia Chien Hanna G. Zimmermann Klemens Ruprecht Tanja Schmitz-Hübsch Judith Bellmann-Strobl Friedemann Paul Vanessa A. Morais |
| author_facet | Filipe Cortes-Figueiredo Susanna Asseyer Claudia Chien Hanna G. Zimmermann Klemens Ruprecht Tanja Schmitz-Hübsch Judith Bellmann-Strobl Friedemann Paul Vanessa A. Morais |
| author_sort | Filipe Cortes-Figueiredo |
| collection | DOAJ |
| description | Abstract Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), with a largely unknown etiology, where mitochondrial dysfunction likely contributes to neuroaxonal loss and brain atrophy. Mirroring the CNS, peripheral immune cells from patients with MS, particularly CD4+ T cells, show inappropriate mitochondrial phenotypes and/or oxidative phosphorylation (OxPhos) insufficiency, with a still unknown contribution of mitochondrial DNA (mtDNA). We hypothesized that mitochondrial genotype in CD4+ T cells might influence MS disease activity and progression. Thus, we performed a retrospective cross-sectional and longitudinal study on patients with a recent diagnosis of either Clinically Isolated Syndrome (CIS) or Relapsing–Remitting MS (RRMS) at two timepoints: 6 months (VIS1) and 36 months (VIS2) after disease onset. Our primary outcomes were the differences in mtDNA extracted from CD4+ T cells between: (I) patients with CIS/RRMS (PwMS) at VIS1 and age- and sex-matched healthy controls (HC), in the cross-sectional analysis, and (II) different diagnostic evolutions in PwMS from VIS1 to VIS2, in the longitudinal analysis. We successfully performed mtDNA whole genome sequencing (mean coverage: 2055.77 reads/base pair) in 183 samples (61 triplets). Nonetheless, mitochondrial genotype was not associated with a diagnosis of CIS/RRMS, nor with longitudinal diagnostic evolution. |
| first_indexed | 2024-04-24T16:17:48Z |
| format | Article |
| id | doaj.art-979abfe0374e42a29c8da6d3ae53c51e |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T16:17:48Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-979abfe0374e42a29c8da6d3ae53c51e2024-03-31T11:21:04ZengNature PortfolioScientific Reports2045-23222024-03-0114111310.1038/s41598-024-57592-zCD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysisFilipe Cortes-Figueiredo0Susanna Asseyer1Claudia Chien2Hanna G. Zimmermann3Klemens Ruprecht4Tanja Schmitz-Hübsch5Judith Bellmann-Strobl6Friedemann Paul7Vanessa A. Morais8Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de LisboaExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinDepartment of Neurology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of HealthExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinExperimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité – Universitätsmedizin BerlinInstituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de LisboaAbstract Multiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), with a largely unknown etiology, where mitochondrial dysfunction likely contributes to neuroaxonal loss and brain atrophy. Mirroring the CNS, peripheral immune cells from patients with MS, particularly CD4+ T cells, show inappropriate mitochondrial phenotypes and/or oxidative phosphorylation (OxPhos) insufficiency, with a still unknown contribution of mitochondrial DNA (mtDNA). We hypothesized that mitochondrial genotype in CD4+ T cells might influence MS disease activity and progression. Thus, we performed a retrospective cross-sectional and longitudinal study on patients with a recent diagnosis of either Clinically Isolated Syndrome (CIS) or Relapsing–Remitting MS (RRMS) at two timepoints: 6 months (VIS1) and 36 months (VIS2) after disease onset. Our primary outcomes were the differences in mtDNA extracted from CD4+ T cells between: (I) patients with CIS/RRMS (PwMS) at VIS1 and age- and sex-matched healthy controls (HC), in the cross-sectional analysis, and (II) different diagnostic evolutions in PwMS from VIS1 to VIS2, in the longitudinal analysis. We successfully performed mtDNA whole genome sequencing (mean coverage: 2055.77 reads/base pair) in 183 samples (61 triplets). Nonetheless, mitochondrial genotype was not associated with a diagnosis of CIS/RRMS, nor with longitudinal diagnostic evolution.https://doi.org/10.1038/s41598-024-57592-z |
| spellingShingle | Filipe Cortes-Figueiredo Susanna Asseyer Claudia Chien Hanna G. Zimmermann Klemens Ruprecht Tanja Schmitz-Hübsch Judith Bellmann-Strobl Friedemann Paul Vanessa A. Morais CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis Scientific Reports |
| title | CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis |
| title_full | CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis |
| title_fullStr | CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis |
| title_full_unstemmed | CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis |
| title_short | CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis |
| title_sort | cd4 t cell mitochondrial genotype in multiple sclerosis a cross sectional and longitudinal analysis |
| url | https://doi.org/10.1038/s41598-024-57592-z |
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