Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis

Background: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin + T-helper cells (Eomes + Th cells) are known to mediate neuroinflammation and disease progression in...

Full description

Bibliographic Details
Main Authors: Simon Faissner, Marielena Bongert, Paulina Trendelenburg, Sandra Thiel, Takashi Yamamura, Kerstin Hellwig, Ralf Gold
Format: Article
Language:English
Published: SAGE Publishing 2024-02-01
Series:Therapeutic Advances in Neurological Disorders
Online Access:https://doi.org/10.1177/17562864241229321
_version_ 1797304930553298944
author Simon Faissner
Marielena Bongert
Paulina Trendelenburg
Sandra Thiel
Takashi Yamamura
Kerstin Hellwig
Ralf Gold
author_facet Simon Faissner
Marielena Bongert
Paulina Trendelenburg
Sandra Thiel
Takashi Yamamura
Kerstin Hellwig
Ralf Gold
author_sort Simon Faissner
collection DOAJ
description Background: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin + T-helper cells (Eomes + Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells. Objectives: Here, investigated immune cell alterations and the pathophysiological role of Eomes + Th cells for disease activity during pregnancy and post-partum in MS. Methods: We enrolled n  = 81 pregnant patients with relapsing-remitting MS (RRMS), n  = 27 post-partum RRMS and n  = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry. Results: While CD3 + CD4 + Th cells were unaffected, CD3 + CD8 + cytotoxic T-cells were elevated post-partum ( p  = 0.02) with reduced B-cell frequencies ( p  = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( p  = 0.02) compared to the third trimester. Frequencies of Eomes + Th and Eomes + Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes + Th cells. However, Eomes + Th cells correlated with lower frequencies of regulatory T-cells during second ( r  = −0.42; p  < 0.05) and third trimester ( r  = −0.37; p  < 0.05). Moreover, Eomes + Th cells correlated with frequencies of B-cells during third trimester ( r  = 0.54; p  = 0.02). Frequencies of Eomes + Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes + Th cells strongly correlated with disability post-partum as assessed using the EDSS ( r  = 0.52; p  = 0.009). Discussion: Pregnancy in MS is associated with robust immunological alterations. Eomes + Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes + Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.
first_indexed 2024-03-08T00:16:31Z
format Article
id doaj.art-def04d32359b4f41adfa56938d6d416f
institution Directory Open Access Journal
issn 1756-2864
language English
last_indexed 2024-03-08T00:16:31Z
publishDate 2024-02-01
publisher SAGE Publishing
record_format Article
series Therapeutic Advances in Neurological Disorders
spelling doaj.art-def04d32359b4f41adfa56938d6d416f2024-02-17T02:04:33ZengSAGE PublishingTherapeutic Advances in Neurological Disorders1756-28642024-02-011710.1177/17562864241229321Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosisSimon FaissnerMarielena BongertPaulina TrendelenburgSandra ThielTakashi YamamuraKerstin HellwigRalf GoldBackground: Pregnancy in patients with multiple sclerosis (MS) is accompanied by a decline of relapse activity with increased risk of relapses 3 months post-partum, for unknown reasons. Eomesodermin + T-helper cells (Eomes + Th cells) are known to mediate neuroinflammation and disease progression in MS and are induced by prolactin-secreting cells. Objectives: Here, investigated immune cell alterations and the pathophysiological role of Eomes + Th cells for disease activity during pregnancy and post-partum in MS. Methods: We enrolled n  = 81 pregnant patients with relapsing-remitting MS (RRMS), n  = 27 post-partum RRMS and n  = 26 female RRMS control patients under the umbrella of the German Multiple Sclerosis and Pregnancy Registry. Clinical data were collected and immune cell alterations were analysed using flow cytometry. Results: While CD3 + CD4 + Th cells were unaffected, CD3 + CD8 + cytotoxic T-cells were elevated post-partum ( p  = 0.02) with reduced B-cell frequencies ( p  = 0.01) compared to non-pregnant RRMS patients. NK cells were elevated during first trimester ( p  = 0.02) compared to the third trimester. Frequencies of Eomes + Th and Eomes + Tc cells did not differ. There was no correlation of prolactin release and expression of Eomes + Th cells. However, Eomes + Th cells correlated with lower frequencies of regulatory T-cells during second ( r  = −0.42; p  < 0.05) and third trimester ( r  = −0.37; p  < 0.05). Moreover, Eomes + Th cells correlated with frequencies of B-cells during third trimester ( r  = 0.54; p  = 0.02). Frequencies of Eomes + Th cells were not associated with the number of relapses before pregnancy, during pregnancy or post-partum. However, Eomes + Th cells strongly correlated with disability post-partum as assessed using the EDSS ( r  = 0.52; p  = 0.009). Discussion: Pregnancy in MS is associated with robust immunological alterations. Eomes + Th cells are capable of inducing immune cell alterations during the course of pregnancy, most evident during the second and third trimester as shown with a correlation of reduced Treg cells and a significant increase of B-cells. Importantly, Eomes + Th cells correlate with disability post-partum. In summary, during late pregnancy in MS an inflammatory, cytotoxic and dysregulated immunological environment is primed gaining function post-delivery. This may be responsible for post-partum disability accumulation.https://doi.org/10.1177/17562864241229321
spellingShingle Simon Faissner
Marielena Bongert
Paulina Trendelenburg
Sandra Thiel
Takashi Yamamura
Kerstin Hellwig
Ralf Gold
Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
Therapeutic Advances in Neurological Disorders
title Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
title_full Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
title_fullStr Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
title_full_unstemmed Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
title_short Eomesodermin-expressing CD4+ Th cells and association with pregnancy in multiple sclerosis
title_sort eomesodermin expressing cd4 th cells and association with pregnancy in multiple sclerosis
url https://doi.org/10.1177/17562864241229321
work_keys_str_mv AT simonfaissner eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT marielenabongert eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT paulinatrendelenburg eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT sandrathiel eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT takashiyamamura eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT kerstinhellwig eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis
AT ralfgold eomesoderminexpressingcd4thcellsandassociationwithpregnancyinmultiplesclerosis