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 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.
Competing Interests: SF has received speaker’s and/or scientific board honoraria from AstraZeneca, Biogen, BMS, Celgene, Janssen, Merck, Novartis and Roche; and grant support from Ruhr-University Bochum, DMSG, Stiftung für therapeutische Forschung, Lead Discovery Center GmbH and Novartis. MB and PT have received funding from the FoRUM-program of the Medical Faculty of Ruhr-University Bochum. ST has nothing to disclose. TY has received speaker honoraria from Biogen, Novartis, Chugai, Takeda, Mitsubishi-Tanabe, Miyarisan and Sumitomo Pharma; serves on the editorial boards of Therapeutic Advances in Neurological Diseases and Clinical and Experimental Neuroimmunology; receives research support from Novartis and Chiome Bioscience; and receives royalties from EA Pharma. KH has received travel grants from Biogen, Novartis and Merck; and received speaker and research honoraria from Biogen Idec Germany, Teva, Sanofi Genzyme, Novartis, Bayer Health-Care, Merck Serono and Roche. RG serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen, Bayer Schering Pharma and Novartis; has received speaker honoraria from Biogen, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives research support from Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, Genzyme, Merck Serono and Novartis. Because RG is Editor-in-Chief of this journal, the peer review process was managed by alternative members of the Board and the submitting Editor was not involved in the decision-making process.
(© The Author(s), 2024.)