Similar Spatial Expression of Immune-Related Proteins in SARS-CoV-2 Placentitis and Chronic Histiocytic Intervillositis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the placenta can lead to fetal distress and demise, characterized by severe trophoblast necrosis, chronic histiocytic intervillositis (CHI), and massive perivillous fibrin deposition. We aimed to uncover spatial immune-related protein changes in SARS-CoV-2 placentitis compared with CHI placentas and uncomplicated pregnancies to gain insight into the underlying pathophysiological mechanisms. Placentas were retrospectively collected from cases with SARS-CoV-2 placentitis resulting in fetal distress/demise (n = 9), CHI (n = 9), and uncomplicated term controls (n = 9).

Maternal microchimeric cell trafficking and its biological consequences depend on the onset of inflammation at the feto-maternal interface.

Microchimerism is defined as the presence of a small population of genetically distinct cells within a host that is derived from another individual. Throughout pregnancy, maternal and fetal cells are known to traffic across the feto-maternal interface and result in maternal and fetal microchimerism, respectively. However, the routes of cell transfer, the molecular signaling as well as the timing in which trafficking takes place are still not completely understood.

Oocyte donation pregnancies with high fetal-maternal immunogenetic dissimilarity show alterations in the maternal peripheral immunoregulatory response.

Oocyte donation (OD) pregnancies result in increased fetal-maternal immunogenetic dissimilarity due to paternal and donor-derived genes. Higher fetal-maternal HLA mismatches are correlated with preeclampsia. Therefore, this study explored the maternal immune response, focusing on regulatory T cells (Tregs) during low versus high allogeneic pregnancies, and healthy versus preeclamptic OD pregnancies.

Foetal Microchimerism Correlates With Foetal-Maternal Histocompatibility Both During Pregnancy and Postpartum.

Foetal cells are detectable in women decades postpartum, a state termed foetal microchimerism. The interplay between these semi-allogeneic foetal cells and the mother could be affected by genetic mismatches in the HLA loci. Here, we relate HLA allele and molecular mismatch values to the presence and quantity of foetal microchimerism in the maternal circulation during pregnancy and postpartum.

Tregs from human blood differentiate into nonlymphoid tissue-resident effector cells upon TNFR2 costimulation.

Tregs can facilitate transplant tolerance and attenuate autoimmune and inflammatory diseases. Therefore, it is clinically relevant to stimulate Treg expansion and function in vivo and to create therapeutic Treg products in vitro. We report that TNF receptor 2 (TNFR2) is a unique costimulus for naive, thymus-derived Tregs (tTregs) from human blood that promotes their differentiation into nonlymphoid tissue-resident (NLT-resident) effector Tregs, without Th-like polarization.

Inflammatory placental lesions are specifically observed in healthy oocyte donation pregnancies with extreme fetal-maternal incompatibility.

Introduction: Oocyte donation (OD) pregnancy is a risk factor for pre-eclampsia (PE). Due to a higher extent of fetal-maternal human leukocyte antigens (HLA) mismatching in OD pregnancies compared to naturally conceived (NC) and in vitro fertilization (IVF) pregnancies, the immune response in OD placentas is probably divergent and affects clinical outcomes. We hypothesized that placental pathology varies among diverse pregnancy conditions and is related to fetal-maternal HLA incompatibility.

MIF Increases sFLT1 Expression in Early Uncomplicated Pregnancy and Preeclampsia.

Insufficient immune tolerance during pregnancy is associated with pathological conditions such as preeclampsia (PE). Soluble fms-like tyrosine kinase-1 (sFLT1), which exerts a role in the late stage of PE, has shown its beneficial anti-inflammatory effects in inflammation-associated diseases. Macrophage migration inhibitory factor (MIF) was reported to upregulate sFLT1 production in experimental congenital diaphragmatic hernia.

Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis.

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68 cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance.

The Mac Is Back: The Role of Macrophages in Human Healthy and Complicated Pregnancies.

Pregnancy is a fascinating immunological paradox: the semi-allogeneic fetus generally grows without any complications. In the placenta, fetal trophoblast cells come into contact with maternal immune cells. Inaccurate or inadequate adaptations of the maternal immune system could lead to problems with the functioning of the placenta.

The severity of chronic histiocytic intervillositis is associated with gestational age and fetal weight.

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta that is associated with poor reproductive outcomes. The intervillous infiltrate consists mostly of maternal mononuclear cells and fibrin depositions, which are both indicators for the severity of the intervillous infiltrate. The severity of the intervillous infiltrate as well as the clinical outcomes of pregnancy differ between cases.

Soluble HLA-G blood levels are not increased during ongoing pregnancy in women with a history of recurrent pregnancy loss.

Recurrent pregnancy loss (RPL) affects 1-2 % of couples who are trying to conceive. At some point, some couples do maintain a healthy pregnancy to term, but the underlying mechanism of RPL remains elusive. Human leukocyte antigen (HLA)-G is an immune modulatory molecule.

Imaging mass cytometry reveals the prominent role of myeloid cells at the maternal-fetal interface.

Although the immunological complexity of the maternal-fetal interface is well appreciated, the actual interaction of maternal immune cells and fetal trophoblasts is insufficiently understood. To comprehend the composition and spatial orientation of maternal immune cells and fetal extravillous trophoblasts, we applied imaging mass cytometry on decidua basalis of the three trimesters of healthy pregnancy. Within all trimesters, we observed considerably higher frequencies of myeloid cells in the decidua than is seen with single-cell suspension techniques.

Primary Trophoblast Cultures: Characterization of HLA Profiles and Immune Cell Interactions.

Introduction: Trophoblasts are essential in fetal-maternal interaction during pregnancy. The goal was to study HLA profiles of primary trophoblasts derived from placentas, and to investigate their usefulness in studying interaction with immune cells.

Methods: After enzymatic digestion of first-trimester placental tissue from seven donors (6-9 weeks gestation) and trophoblast enrichment we cultured cytotrophoblasts (CTB) in stem cell medium.

Circulating Levels of Anti-C1q and Anti-Factor H Autoantibodies and Their Targets in Normal Pregnancy and Preeclampsia.

Preeclampsia (PE) generally manifests in the second half of pregnancy with hypertension and proteinuria. The understanding of the origin and mechanism behind PE is incomplete, although there is clearly an immune component to this disorder. The placenta constitutes a complicated immune interface between fetal and maternal cells, where regulation and tolerance are key.

Impaired immunomodulatory effects of seminal plasma may play a role in unexplained recurrent pregnancy loss: Results of an in vitro study.

Background: Seminal plasma contains signaling molecules capable of modulating the maternal immune environment to support implantation and pregnancy. Prior studies indicated that seminal plasma induces changes in gene transcription of maternal immune cells. Reduced immune suppressive capacity may lead to pregnancy loss.

Different immunoregulatory components at the decidua basalis of oocyte donation pregnancies.

Oocyte donation (OD) pregnancies are characterized by more fetal-maternal human leukocyte antigen (HLA) mismatches compared with naturally conceived (NC) and in vitro fertilization (IVF) pregnancies. The maternal immune system has to cope with greater immunogenetic dissimilarity, but involved immunoregulation remains poorly understood. We examined whether the amount of regulatory T cells (Tregs) and immunoregulatory cytokines in decidua basalis of OD pregnancies differs from NC and IVF pregnancies.

Uncomplicated oocyte donation pregnancies display an elevated CD163-positive type 2 macrophage load in the decidua, which is associated with fetal-maternal HLA mismatches.

Problem: The embryo of an oocyte donation (OD) pregnancy is completely allogeneic to the mother, which may challenge the maternal immune system to tolerize the fetus. Decidual macrophages are essential in maintaining a healthy pregnancy, and type 2 macrophages may exhibit immune suppressive activity. We hypothesized that the composition of decidual macrophages is different between uncomplicated OD pregnancies and non-OD in vitro fertilization (IVF) pregnancies, and is related to fetal-maternal incompatibility.

and Its Ligands Show Increased Expression in High-Risk Uveal Melanoma.

Uveal melanoma (UM) is a rare ocular malignancy which originates in the uveal tract, and often gives rise to metastases. Potential targets for immune checkpoint inhibition are lymphocyte-activation gene 3 (LAG3) and its ligands. We set out to analyse the distribution of these molecules in UM.

Identification of distinct seminal plasma cytokine profiles associated with male age and lifestyle characteristics in unexplained recurrent pregnancy loss.

Background: Seminal plasma contains a wide range of cytokines, chemokines and growth factors. Part of these signalling molecules assist in inducing a state of active maternal immune tolerance towards the fetus. Disbalances in seminal plasma content may contribute to pregnancy loss.

Placental Complement Activation in Fetal and Neonatal Alloimmune Thrombocytopenia: An Observational Study.

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a disease that causes thrombocytopenia and a risk of bleeding in the (unborn) child that result from maternal alloantibodies directed against fetal, paternally inherited, human platelet antigens (HPA). It is hypothesized that these alloantibodies can also bind to the placenta, causing placental damage. This study aims to explore signs of antibody-mediated placental damage in FNAIT.

A Combined microRNA and Chemokine Profile in Urine to Identify Rejection After Kidney Transplantation.

Unlabelled: There is an unmet need for noninvasive tools for diagnosis of rejection after kidney transplantation. The aim of this study was to determine the discriminative value of a combined cellular and molecular biomarker platform in urine for the detection of rejection.

Methods: First, microRNA (miR) molecules were screened in transplant biopsies and urine sediments of patients with acute rejection and patients without rejection and stable graft function.

Maternal-Fetal HLA Compatibility in Uncomplicated and Preeclamptic Naturally Conceived Pregnancies.

Introduction: In pregnancy, the mother and fetus differ in HLA antigens, and yet the maternal immune system generally tolerates the fetus. KIR receptors expressed by maternal uterine NK cells at the maternal-fetal interface directly interact with HLA-C on extravillous trophoblast cells for optimal placental development. In this study, we aimed to determine whether there is a preferential selection for HLA compatibility and specific KIR/HLA-C combinations in uncomplicated and preeclamptic naturally conceived pregnancies compared to what would be expected by chance.

A possible role for HLA-G in development of uteroplacental acute atherosis in preeclampsia.

HLA-G, a non-classical HLA molecule expressed by extravillous trophoblasts, plays a role in the maternal immune tolerance towards fetal cells. HLA-G expression is regulated by genetic polymorphisms in the 3' untranslated region (3'UTR). Low levels of HLA-G in the maternal circulation and placental tissue are linked to preeclampsia.

Visualizing Dynamic Changes at the Maternal-Fetal Interface Throughout Human Pregnancy by Mass Cytometry.

During healthy pregnancy, a balanced microenvironment at the maternal-fetal interface with coordinated interaction between various immune cells is necessary to maintain immunological tolerance. While specific decidual immune cell subsets have been investigated, a system-wide unbiased approach is lacking. Here, mass cytometry was applied for data-driven, in-depth immune profiling of the total leukocyte population isolated from first, second, and third trimester decidua, as well as maternal peripheral blood at time of delivery.