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Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis

Beltrán, E; Gerdes, LA; Hansen, J; Flierl-Hecht, A; Krebs, S; Blum, H; Ertl-Wagner, B; ... Dornmair, K; + view all (2019) Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis. JCI 10.1172/JCI128475. (In press). Green open access

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Abstract

Multiple sclerosis (MS) is a disabling disease of the CNS. Inflammatory features of MS include lymphocyte accumulations in the CNS and cerebrospinal fluid (CSF). The preclinical events leading to established MS are still enigmatic. Here we compared gene expression patterns of CSF cells from MS-discordant monozygotic twin pairs. Six "healthy" co-twins, who carry a maximal familial risk for developing MS, showed subclinical neuroinflammation (SCNI) with small MRI lesions. Four of these subjects had oligoclonal bands (OCBs). By single-cell RNA sequencing of 2752 CSF cells, we identified clonally expanded CD8+ T cells, plasmablasts, and, to a lesser extent, CD4+ T cells not only from MS patients but also from subjects with SCNI. In contrast to nonexpanded T cells, clonally expanded T cells showed characteristics of activated tissue-resident memory T (TRM) cells. The TRM-like phenotype was detectable already in cells from SCNI subjects but more pronounced in cells from patients with definite MS. Expanded plasmablast clones were detected only in MS and SCNI subjects with OCBs. Our data provide evidence for very early concomitant activation of 3 components of the adaptive immune system in MS, with a notable contribution of clonally expanded TRM-like CD8+ cells.

Type: Article
Title: Early adaptive immune activation detected in monozygotic twins with prodromal multiple sclerosis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/JCI128475
Publisher version: http://doi.org/10.1172/JCI128475
Language: English
Additional information: This version is the version of record. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Adaptive immunity, Immunology, Multiple sclerosis, Neuroscience
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation
URI: https://discovery.ucl.ac.uk/id/eprint/10083094
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