Alterations of NK Cell Phenotype During Pregnancy in Multiple Sclerosis

Abstract

In multiple sclerosis (MS), relapse rate is decreased by 70-80% in the third trimester of pregnancy. However, the underlying mechanisms driving this effect are poorly understood. Evidence suggests that CD56bright NK cell frequencies increase during pregnancy. Here, we analyze pregnancy-related NK cell shifts in a large longitudinal cohort of pregnant women with and without MS, and provide in-depth phenotyping of NK cells. In healthy pregnancy and pregnancy in MS, peripheral blood NK cells showed significant frequency shifts, notably an increase of CD56bright NK cells and a decrease of CD56dim NK cells toward the third trimester, indicating a general rather than an MS-specific phenomenon of pregnancy. Additional follow-ups in women with MS showed a reversal of NK cell changes postpartum. Moreover, high-dimensional profiling revealed a specific CD56bright subset with receptor expression related to cytotoxicity and cell activity (e.g., CD16+ NKp46high NKG2Dhigh NKG2Ahigh phenotype) that may drive the expansion of CD56bright NK cells during pregnancy in MS. Our data confirm that pregnancy promotes pronounced shifts of NK cells toward the regulatory CD56bright population. Although exploratory results on in-depth CD56bright phenotype need to be confirmed in larger studies, our findings suggest an increased regulatory NK activity, thereby potentially contributing to disease amelioration of MS during pregnancy.

Characterization of Natural Killer Cell Profile in a Cohort of Infected Pregnant Women and Their Babies and Its Relation to CMV Transmission

“…Although this cohort offers a valuable opportunity to gather preliminary insights, another limitation is represented by the variable sampling time in pregnant mothers. As reported by Wisgalla A et al, in healthy pregnancy peripheral blood, NK cells showed an increase in CD56bright and a decrease in CD56dim populations toward the third trimester [42]. In our cohort, CD56dim population frequency was not affected by third trimester sampling.…”

NK Cell Levels Correlate with Disease Activity in Patients with Multiple Sclerosis on Ocrelizumab/Rituximab Therapy

“…No concordant or discordant evidence of these findings can be found in the literature. However, Wisgalla et al [ 15 ] showed that percentage levels of NK cells increase during pregnancy of MS patients while decreasing significantly in the postpartum period [ 15 ]. Based on the assumption that pregnancy is protective against disease activity while postpartum increases the risk of MS reactivation [ 16 ], our data would be in line with the literature, confirming the protective effect of a higher percentage of NK cells on MS.…”

The Role of NKG2D and Its Ligands in Autoimmune Diseases: New Targets for Immunotherapy

“…In women with MS, the NK cells are reversed postpartum [80]. Pregnancy was found to promote the marked transformation of NK cells into a regulatory CD56 bright NK cell population that expressed receptors associated with cytotoxicity (such as the CD16 + NKp46 high NKG2D high NKG2A high phenotype) [80]. ULBP4 was found to be predominantly expressed by astrocytes rather than neurons [81].…”