Decreased expression of ligands of placental immune checkpoint inhibitors in uncomplicated and preeclamptic oocyte donation pregnancies

Hof, Liseanne J. van 't; Dijkstra, Kyra L.; Keur, Carin van der; Eikmans, Michael; Baelde, Hans J.; Bos, Manon; Hoorn, Marie-Louise van der

doi:10.1016/j.jri.2020.103194

Cited by 8 publications

(8 citation statements)

References 42 publications

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“…Preeclamptic patients after oocyte donation showed lower PD-L1 and CD200 protein expression compared to naturally conceived patients. These alterations might contribute to the higher risk of developing preeclampsia after oocyte donation [25].…”

Section: The Pd-1/pd-l1 System In Normal Pregnancymentioning

confidence: 99%

The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

et al. 2022

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Preeclampsia is a pregnancy-specific disease which is characterized by abnormal placentation, endothelial dysfunction, and systemic inflammation. Several studies have shown that the maternal immune system, which is crucial for maintaining the pregnancy by ensuring maternal-fetal-tolerance, is disrupted in preeclamptic patients. Besides different immune cells, immune checkpoint molecules such as the programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1 system) and the T-cell immunoglobulin and mucin domain-containing protein 3/Galectin-9 (TIM-3/Gal-9 system) are key players in upholding the balance between pro-inflammatory and anti-inflammatory signals. Therefore, a clear understanding about the role of these immune checkpoint molecules in preeclampsia is essential. This review discusses the role of these two immune checkpoint systems in pregnancy and their alterations in preeclampsia.

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Section: The Pd-1/pd-l1 System In Normal Pregnancymentioning

confidence: 99%

The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

et al. 2022

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“…In addition, significantly lower CD200 expression was noted in oocyte donation pregnancies with preeclampsia compared to those without preeclampsia, and this was not observed in naturally conceived pregnancies (33). Similarly, in preeclampsia pregnancies, significantly lower CD200 expression was noted in oocyte donation pregnancies compared to naturally conceived pregnancies (33). Thus, CD200 might have a role in the gestation processes of oocyte donation pregnancies.…”

Section: Discussionmentioning

confidence: 87%

Significance of placental CD200 expression in patients with preeclampsia: Comparison between early‑ and late‑onset patients

et al. 2022

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Preeclampsia, characterized by high blood pressure and proteinuria during pregnancy, causes serious complications in both the mother and the fetus. Although there have been several studies on the causes of preeclampsia, the detailed mechanism of this disease remains unclear. Moreover, a few reports have focused on the causes of preeclampsia in number of weeks at onset. The present study aimed to elucidate the differences between early-and late-onset preeclampsia. This study enrolled patients with preeclampsia from January 2014 to December 2020. They were classified into early-(<34 weeks) and late-onset (≥34 weeks) preeclampsia groups. The expression profiles of 770 immune-related genes were studied in the placental tissue from five patients each in the early-and late-onset groups. The expression of CD200 in the trophoblasts of the placenta of 26 and 27 patients in early-and late-onset groups, respectively, was also analyzed using immunostaining. Analysis of extracted RNA indicated that CD200 was significantly upregulated in the early-onset group compared with late-onset group and normal control. Immunostaining for CD200 demonstrated a significantly increased expression in the early-onset group compared with the late-onset group. The present study demonstrated that upregulation of CD200, which belongs to the immunoglobulin superfamily and is recognized as a molecule that acts in immune tolerance via inhibition of classical macrophage activation, may be associated with early-onset preeclampsia, although it remains unknown whether upregulation of CD200 expression is a cause or effect of the development of early-onset preeclampsia. Early-onset preeclampsia might have a different mechanism from that of late-onset; thus, further studies are needed to clarify the mechanism of these conditions for adequate treatment.

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“…This mechanism might have a role in letting the immune system react to the Th1 predominance during EO preeclampsia. Since the systemic immune response is probably a reflection of the local immune alterations observed at the materno-fetal interface (MFI), recent studies showed the importance of immune checkpoint molecules present locally [ 40 , 41 , 42 ]. There is no available data regarding the potential role of TIGIT/CD226/CD112/CD155 molecules at the MFI, but it needs further investigation.…”

Section: Discussionmentioning

confidence: 99%

Examination of the TIGIT, CD226, CD112, and CD155 Immune Checkpoint Molecules in Peripheral Blood Mononuclear Cells in Women Diagnosed with Early-Onset Preeclampsia

et al. 2021

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Early-onset preeclampsia is a common obstetrical disease with a potential genetic background and is characterized by the predominance of Th1 immune response. However, although many studies investigated the immunological environment in preeclamptic patients, no information is available about the potential role of the TIGIT/CD226/CD112/CD155 immune checkpoint pathway. A total of 37 pregnant women diagnosed with early-onset preeclampsia and 36 control women with appropriately matched gestational age were enrolled in this study. From venous blood, mononuclear cells were isolated and stored in the freezer. Using multicolor flow cytometry T-, NK cell and monocyte subpopulations were determined. After characterization of the immune cell subsets, TIGIT, CD226, CD112, and CD155 surface expression and intracellular granzyme B content were determined by flow cytometer. Significantly decreased CD226 expression and increased CD112 and CD155 surface expression were detected in almost all investigated T-cell, NK cell, and monocyte subpopulations in women diagnosed with preeclampsia compared to the healthy group. Furthermore, reduced TIGIT and granzyme B expression were measured only in preeclamptic CD8+ T cells compared to healthy pregnant women. A decreased level of the activatory receptor CD226 in effector lymphocytes accompanied with an elevated surface presence of the CD112 and CD155 ligands in monocytes could promote the TIGIT/CD112 and/or TIGIT/CD155 ligation, which mediates inhibitory signals. We assume that the inhibition of the immune response via this immune checkpoint pathway might contribute to compensate for the Th1 predominance during early-onset preeclampsia.

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Decreased expression of ligands of placental immune checkpoint inhibitors in uncomplicated and preeclamptic oocyte donation pregnancies

Cited by 8 publications

References 42 publications

The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

The Role of the Immune Checkpoint Molecules PD-1/PD-L1 and TIM-3/Gal-9 in the Pathogenesis of Preeclampsia—A Narrative Review

Significance of placental CD200 expression in patients with preeclampsia: Comparison between early‑ and late‑onset patients

Examination of the TIGIT, CD226, CD112, and CD155 Immune Checkpoint Molecules in Peripheral Blood Mononuclear Cells in Women Diagnosed with Early-Onset Preeclampsia

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