dc.contributor.author
Schwichtenberg, Svenja C.
dc.contributor.author
Wisgalla, Anne
dc.contributor.author
Schroeder-Castagno, Maria
dc.contributor.author
Alvarez-González, Cesar
dc.contributor.author
Schlickeiser, Stephan
dc.contributor.author
Siebert, Nadja
dc.contributor.author
Bellmann-Strobl, Judith
dc.contributor.author
Wernecke, Klaus-Dieter
dc.contributor.author
Paul, Friedemann
dc.contributor.author
Dörr, Jan
dc.contributor.author
Infante-Duarte, Carmen
dc.date.accessioned
2023-07-18T11:46:56Z
dc.date.available
2023-07-18T11:46:56Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/40143
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-39865
dc.description.abstract
Fingolimod is an approved oral treatment for relapsing-remitting multiple sclerosis (RRMS) that modulates agonistically the sphingosin-1-phosphate receptor (S1PR), inhibiting thereby the egress of lymphocytes from the lymph nodes. In this interventional prospective clinical phase IV trial, we longitudinally investigated the impact of fingolimod on frequencies of NK cell subpopulations by flow cytometry in 17 RRMS patients at baseline and 1, 3, 6, and 12 months after treatment initiation. Clinical outcome was assessed by the Expanded Disability Status Scale (EDSS) and annualized relapse rates (ARR). Over the study period, median EDSS remained stable from month 3 to month 12, and ARR decreased compared to ARR in the 24 months prior treatment. Treatment was paralleled by an increased frequency of circulating NK cells, due primarily to an increase in CD56(dim)CD94(low) mature NK cells, while the CD56(bright) fraction and CD127(+) innate lymphoid cells (ILCs) decreased over time. An unsupervised clustering algorithm further revealed that a particular fraction of NK cells defined by the expression of CD56(dim)CD16(++)KIR(+/-)NKG2A(-)CD94(-)CCR7(+/-)CX(3)CR1(+/-)NKG2C(-)NKG2D(+)NKp46(-)DNAM1(++)CD127(+) increased during treatment. This specific phenotype might reflect a status of aged, fully differentiated, and less functional NK cells. Our study confirms that fingolimod treatment affects both NK cells and ILC. In addition, our study suggests that treatment leads to the enrichment of a specific NK cell subset characterized by an aged phenotype. This might limit the anti-microbial and anti-tumour NK cell activity in fingolimod-treated patients.
en
dc.rights.uri
https://creativecommons.org/licenses/by/4.0/
dc.subject
Natural killer (NK) cells
en
dc.subject
Multiple sclerosis (MS)
en
dc.subject
Innate lymphoid cells (ILCs)
en
dc.subject
Sphingosin-1-phosphate receptor (S1PR)
en
dc.subject.ddc
600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit
dc.title
Fingolimod Therapy in Multiple Sclerosis Leads to the Enrichment of a Subpopulation of Aged NK Cells
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1007/s13311-021-01078-7
dcterms.bibliographicCitation.journaltitle
Neurotherapeutics
dcterms.bibliographicCitation.number
3
dcterms.bibliographicCitation.originalpublishername
Springer Nature
dcterms.bibliographicCitation.pagestart
1783
dcterms.bibliographicCitation.pageend
1797
dcterms.bibliographicCitation.volume
18
refubium.affiliation
Charité - Universitätsmedizin Berlin
refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.bibliographicCitation.pmid
34244929
dcterms.isPartOf.issn
1933-7213
dcterms.isPartOf.eissn
1878-7479