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

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Item Type:Article
Title:CD4+ T cell mitochondrial genotype in Multiple Sclerosis: a cross-sectional and longitudinal analysis
Creators Name:Cortes-Figueiredo, F., Asseyer, S., Chien, C., Zimmermann, H.G., Ruprecht, K., Schmitz-Hübsch, T., Bellmann-Strobl, J., Paul, F. and Morais, V.A.
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.
Keywords:CD4-Positive T-Lymphocytes, Cross-Sectional Studies, Mitochondrial DNA, Demyelinating Diseases, Genotype, Longitudinal Studies, Multiple Sclerosis, Relapsing-Remitting Multiple Sclerosis, Retrospective Studies, T-Lymphocytes
Source:Scientific Reports
ISSN:2045-2322
Publisher:Nature Publishing Group
Volume:14
Number:1
Page Range:7507
Date:29 March 2024
Official Publication:https://doi.org/10.1038/s41598-024-57592-z
PubMed:View item in PubMed

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