CD4 + T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis.

Autor: Cortes-Figueiredo F; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal.; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Asseyer S; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Chien C; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Zimmermann HG; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; Einstein Center Digital Future, Berlin, Germany., Ruprecht K; Department of Neurology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Schmitz-Hübsch T; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Bellmann-Strobl J; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany., Paul F; Experimental and Clinical Research Center, a Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité - Universitätsmedizin Berlin, Berlin, Germany. friedemann.paul@charite.de.; NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. friedemann.paul@charite.de., Morais VA; Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal. vmorais@medicina.ulisboa.pt.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Mar 29; Vol. 14 (1), pp. 7507. Date of Electronic Publication: 2024 Mar 29.
DOI: 10.1038/s41598-024-57592-z
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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