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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.

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