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

Abstract

2.AbstractMultiple Sclerosis (MS) is a chronic autoimmune demyelinating disease of the central nervous system (CNS), with a largely unknown etiology, where mitochondrial dysfunction significantly 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: six 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 (WGS) (mean coverage: 2055.77 reads/base pair) in 183 samples (61 triplets). Nonetheless, mitochondrial genotype was not associated with a diagnostic of CIS/RRMS, nor with longitudinal diagnostic evolution.