Paternal <scp>HLA</scp>‐C is a risk factor in unexplained recurrent miscarriage

Meuleman, Tess; Haasnoot, Geert W.; Lith, J. M. M. van; Verduijn, Willem; Bloemenkamp, Kitty W. M.; Claas, Frans H.J.

doi:10.1111/aji.12797

Cited by 16 publications

(11 citation statements)

References 40 publications

(43 reference statements)

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“…Moreover, both CD69 and CD103, that can prevent cell egress and are expressed at a higher level by mucosal memory T cells than circulating memory T cells ( 44 , 46 , 47 ), were observed to be upregulated in human dCD8 cells (Figure 3 ; Figures S6 and S7 in Supplementary Material), indicating that these cells have a “tissue-resident effector-memory T cell” (T REM ) phenotype during human early pregnancy. Although memory dCD8 T cells were hypothesized to be virus-specific T cells to protect the fetus against invading pathogens in uncomplicated pregnancy ( 48 ), the definite role and specificity of these dCD8 T REM cells remain largely unknown and need to be determined by more experiments.…”

Section: Discussionmentioning

confidence: 99%

Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy

Zeng

Liu

et al. 2018

Front. Immunol.

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Decidual CD8+ (dCD8) T cells have been proposed to play important roles in immune protection against the invading pathogens and in tolerance toward the growing semi-allogeneic fetus during early pregnancy. However, their phenotypic and functional characteristics remain poorly defined. Here, we performed the first analysis of the transcriptional and alternative splicing (AS) signatures for human first-trimester dCD8 T cells using high-throughput mRNA sequencing. Our data revealed that dCD8 T cells have distinct transcriptional and AS landscapes when compared with their autologous peripheral blood CD8+ (pCD8) T counterparts. Furthermore, human dCD8 T cells were observed to contain CD8-Treg and effector-memory T-cell subsets, and display enhanced functionality in terms of degranulation and cytokine production on a per-cell basis. Additionally, we have identified the novel splice junctions that use a high ratio of the non-canonical splicing motif GC-AG and found that AS is not a major contributor to the gene expression-level changes between paired pCD8 and dCD8 T cells. Together, our findings not only provide a comprehensive framework of the transcriptional and AS landscapes but also reveal the functional feature of human dCD8 T cells, which are of great importance in understanding the biology of these cells and the physiology of human healthy pregnancy.

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Section: Discussionmentioning

confidence: 99%

Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy

Zeng

Liu

et al. 2018

Front. Immunol.

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“…Thus, it seems that HLA-G contributes to fetal tolerance by modulating decidual NK cell and APC responses (LeMaoult et al., 2004). Such nonclassical MHC molecules are of key importance not only in the establishment of the pregnancy but also in its maintenance, as revealed by studies in both healthy and pathological pregnancies (Tripathi et al., 2006; Michita et al., 2016; Persson et al., 2017; Meuleman et al., 2018). Notably, it has been shown that immunomodulatory molecules from the B7 family and the soluble HLA-G isoform HLA-G5 are secreted from the placenta during the first trimester and at term via exosomes (Kshirsagar et al., 2012).…”

Section: Main Textmentioning

confidence: 99%

Extracellular vesicles in host-pathogen interactions and immune regulation — exosomes as emerging actors in the immunological theater of pregnancy

Kaminski

Ellwanger

Chies

2019

Heliyon

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This review correlates and summarizes the role of the maternal-fetal interface in the immune tolerance of the fetus and the processes that lead to infection avoidance, emphasizing the participation of exosomes and other extracellular vesicles in both situations. Exosomes are released into the extracellular medium by several cell types and are excellent carriers of biomolecules. Host-derived exosomes and the transport of pathogen-derived molecules by exosomes impact infections in different ways. The interactions of exosomes with the maternal immune system are pivotal to a favorable gestational outcome. In this review, we highlight the potential role of exosomes in the establishment of an adequate milieu that enables embryo implantation and discuss the participation of exosomes released at the maternal-fetal interface during the establishment of an immune-privileged compartment for fetal development. The placenta is a component where important strategies are used to minimize the risk of infection. To present a contrast, we also discuss possible mechanisms used by pathogens to cross the maternal-fetal interface. We review the processes, mechanisms, and potential consequences of dysregulation in all of the abovementioned phenomena. Basic information about exosomes and their roles in viral immune evasion is also presented. The interactions between extracellular vesicles and bacteria, fungi, parasites and proteinaceous infectious agents are addressed. The discovery of the placental microbiota and the implications of this new microbiota are also discussed, and current proposals that explain fetal/placental colonization by both pathogenic and commensal microbes are addressed. The comprehension of such interactions will help us to understand the immune dynamics of human pregnancy and the mechanisms of immune evasion used by different pathogens.

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“…And in early pregnancy they are also associated with lower chance of a live birth in women with RM . For example, HLA‐C‐specific antibodies were found more often in women with RM and the reason maybe that they induce platelet activation by placental thromboxane production . Taken together, whether the anti‐HLA antibodies are unrelated or harmful to pregnancy maintenance is still debatable.…”

Section: Antipaternal (Anti‐hla) Antibodiesmentioning

confidence: 99%

Antibodies: The major participants in maternal–fetal interaction

Yang

Zhang

Chen

et al. 2018

J of Obstet and Gynaecol

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The aim of this study is to improve our understanding of the mechanisms involved in maternal-fetal immune tolerance. We searched the related literatures and overviewed the major antibodies associated with pregnancy and described in details their possible roles in mediating maternal-fetal interactions. Antibodies classified into different types based on their functional or structural characteristics were summarized, including immunoglobulin G, blocking antibody, nonprecipitating asymmetric antibody, antiphospholipid antibody, antitrophoblast antibody and antipaternal antibody. The presence and levels of various circulating antibodies in pregnancy may play a crucial role in the occurrence, development and termination of pregnancy.

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Paternal HLA‐C is a risk factor in unexplained recurrent miscarriage

Abstract: The results show that HLA-C incompatibility between couples is significantly associated with unexplained recurrent miscarriage.

Cited by 16 publications

References 40 publications

Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy

Deep Surveying of the Transcriptional and Alternative Splicing Signatures for Decidual CD8+ T Cells at the First Trimester of Human Healthy Pregnancy

Extracellular vesicles in host-pathogen interactions and immune regulation — exosomes as emerging actors in the immunological theater of pregnancy

Antibodies: The major participants in maternal–fetal interaction

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