Twin study reveals non-heritable immune perturbations in multiple sclerosis

Florian Ingelfinger, Lisa Ann Gerdes, Vladyslav Kavaka, Sinduya Krishnarajah, Ekaterina Friebel, Edoardo Galli, Pascale Zwicky, Reinhard Furrer, Christian Peukert (), Charles-Antoine Dutertre, Klara Magdalena Eglseer, Florent Ginhoux, Andrea Flierl-Hecht, Tania Kümpfel, Donatella Feo, Bettina Schreiner, Sarah Mundt, Martin Kerschensteiner, Reinhard Hohlfeld, Eduardo Beltrán and Burkhard Becher ()
Additional contact information
Florian Ingelfinger: University of Zurich
Lisa Ann Gerdes: University Hospital, LMU Munich
Vladyslav Kavaka: University Hospital, LMU Munich
Sinduya Krishnarajah: University of Zurich
Ekaterina Friebel: University of Zurich
Edoardo Galli: University of Zurich
Pascale Zwicky: University of Zurich
Reinhard Furrer: University of Zurich
Charles-Antoine Dutertre: Gustave Roussy Cancer Campus
Klara Magdalena Eglseer: University Hospital, LMU Munich
Florent Ginhoux: Singapore Immunology Network, A*STAR
Andrea Flierl-Hecht: University Hospital, LMU Munich
Tania Kümpfel: University Hospital, LMU Munich
Donatella Feo: University of Zurich
Bettina Schreiner: University of Zurich
Sarah Mundt: University of Zurich
Martin Kerschensteiner: University Hospital, LMU Munich
Reinhard Hohlfeld: University Hospital, LMU Munich
Eduardo Beltrán: University Hospital, LMU Munich
Burkhard Becher: University of Zurich

Nature, 2022, vol. 603, issue 7899, 152-158

Abstract: Abstract Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system underpinned by partially understood genetic risk factors and environmental triggers and their undefined interactions1,2. Here we investigated the peripheral immune signatures of 61 monozygotic twin pairs discordant for MS to dissect the influence of genetic predisposition and environmental factors. Using complementary multimodal high-throughput and high-dimensional single-cell technologies in conjunction with data-driven computational tools, we identified an inflammatory shift in a monocyte cluster of twins with MS, coupled with the emergence of a population of IL-2 hyper-responsive transitional naive helper T cells as MS-related immune alterations. By integrating data on the immune profiles of healthy monozygotic and dizygotic twin pairs, we estimated the variance in CD25 expression by helper T cells displaying a naive phenotype to be largely driven by genetic and shared early environmental influences. Nonetheless, the expanding helper T cells of twins with MS, which were also elevated in non-twin patients with MS, emerged independent of the individual genetic makeup. These cells expressed central nervous system-homing receptors, exhibited a dysregulated CD25–IL-2 axis, and their proliferative capacity positively correlated with MS severity. Together, our matched-pair analysis of the extended twin approach allowed us to discern genetically and environmentally determined features of an MS-associated immune signature.

Date: 2022
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-022-04419-4 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:603:y:2022:i:7899:d:10.1038_s41586-022-04419-4

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-022-04419-4

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().