Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

Ma, Nana; Qin, Rongyan; Qin, Weili; Liao, Ming; Zhao, Yunxiao; Hang, F; Qin, Aiping

doi:10.1111/jcpt.13629

Cited by 8 publications

(5 citation statements)

References 39 publications

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“…As an effective immunosuppressant, CsA is broadly employed in organ transplantation. 78 Now, CsA is also extensively utilized in various pregnancy complications, such as idiopathic or recurrent spontaneous abortion, 79 , 80 repeated implantation failure 81 , 82 and preeclampsia. 83 This therapeutic effect is supposed to be attributed to its widespread modulatory effects on various immunocytes.…”

Section: Discussionmentioning

confidence: 99%

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death

Zhao,

Jiang,

et al. 2023

J Cellular Molecular Medi

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Prenatal tobacco exposure (PTE) correlates significantly with a surge in adverse pregnancy outcomes, yet its pathological mechanisms remain partially unexplored. This study aims to meticulously examine the repercussions of PTE on placental immune landscapes, employing a coordinated research methodology encompassing bioinformatics, machine learning and animal studies. Concurrently, it aims to screen biomarkers and potential compounds that could sensitively indicate and mitigate placental immune disorders. In the course of this research, two gene expression omnibus (GEO) microarrays, namely GSE27272 and GSE7434, were included. Gene set enrichment analysis (GSEA) and immune enrichment investigations on differentially expressed genes (DEGs) indicated that PTE might perturb numerous innate or adaptive immune‐related biological processes. A cohort of 52 immune‐associated DEGs was acquired by cross‐referencing the DEGs with gene sets derived from the ImmPort database. A protein–protein interaction (PPI) network was subsequently established, from which 10 hub genes were extracted using the maximal clique centrality (MCC) algorithm (JUN, NPY, SST, FLT4, FGF13, HBEGF, NR0B2, AREG, NR1I2, SEMA5B). Moreover, we substantiated the elevated affinity of tobacco reproductive toxicants, specifically nicotine and nitrosamine, with hub genes through molecular docking (JUN, FGF13 and NR1I2). This suggested that these genes could potentially serve as crucial loci for tobacco's influence on the placental immune microenvironment. To further elucidate the immune microenvironment landscape, consistent clustering analysis was conducted, yielding three subtypes, where the abundance of follicular helper T cells (p < 0.05) in subtype A, M2 macrophages (p < 0.01), neutrophils (p < 0.05) in subtype B and CD8+ T cells (p < 0.05), resting NK cells (p < 0.05), M2 macrophages (p < 0.05) in subtype C were significantly different from the control group. Additionally, three pivotal modules, designated as red, blue and green, were identified, each bearing a close association with differentially infiltrated immunocytes, as discerned by the weighted gene co‐expression network analysis (WGCNA). Functional enrichment analysis was subsequently conducted on these modules. To further probe into the mechanisms by which immune‐associated DEGs are implicated in intercellular communication, 20 genes serving as ligands or receptors and connected to differentially infiltrating immunocytes were isolated. Employing a variety of machine learning techniques, including one‐way logistic regression, LASSO regression, random forest and artificial neural networks, we screened 11 signature genes from the intersection of immune‐associated DEGs and secretory protein‐encoding genes derived from the Human Protein Atlas. Notably, CCL18 and IFNA4 emerged as prospective peripheral blood markers capable of identifying PTE‐induced immune disorders. These markers demonstrated impressive predictive power, as indicated by the area under the curve (AUC) of 0.713 (0.548–0.857) and 0.780 (0.618–0.914), respectively. Furthermore, we predicted 34 potential compounds, including cyclosporine, oestrogen and so on, which may engage with hub genes and attenuate immune disorders instigated by PTE. The diagnostic performance of these biomarkers, alongside the interventional effect of cyclosporine, was further corroborated in animal studies via ELISA, Western blot and immunofluorescence assays. In summary, this study identifies a disturbance in the placental immune landscape, a secondary effect of PTE, which may underlie multiple pregnancy complications. Importantly, our research contributes to the noninvasive and timely detection of PTE‐induced placental immune disorders, while also offering innovative therapeutic strategies for their treatment.

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Section: Discussionmentioning

confidence: 99%

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death

Zhao,

Jiang,

et al. 2023

J Cellular Molecular Medi

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“…Rate of miscarriage was decreased post-treatment. However, the study reported significant heterogeneity and a moderate-to-severe risk of bias [209].…”

Section: Cyclosporinementioning

confidence: 91%

Recent Advances in Immunotherapeutic Approaches for Recurrent Reproductive Failure

Abdolmohammadi-Vahid¹,

Aghebati‐Maleki²,

Ahmadian-Heris³

et al. 2023

IVF Technologies and Infertility - Current Practices and New Perspectives

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Human reproduction is an insufficient process, disturbed by various factors, such as immunologic aberrations of mother. Immunologic abnormalities, including cellular and humoral immunity imbalance, cause dysregulated immune responses against embryo, fetus, and associated components and lack of maternal immunotolerance, which compromise the maintenance of pregnancy. Therefore, evaluation of immunologic parameters, including cellular and humoral immunity assessment (T and B lymphocyte, T helper subtypes, NK cells, cytokines, and autoantibodies), especially in women with a history of pregnancy loss or implantation failure, would help clinicians to manage the disorder and prevent next unfavorable pregnancy outcomes. Moreover, several immunomodulatory approaches have been introduced to modulate the abnormal immunologic responses in patients who experience reproduction failure, especially those diagnosed with immunologic basis. Anticoagulants, corticosteroids, intravenous immunoglobulin, immunosuppressive medications used in inhibition of graft rejection, such as calcineurin inhibitors, recombinant cytokines, and cell therapy approaches, are among these modalities. Here, we discuss the proposed mechanisms of immunologic abnormalities involved in the etiopathogenesis of reproduction disorders, besides the suggested immunologic tests and immunotherapeutic approaches which may be helpful in management of these disorders.

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“…Steroid treatment was shown to improve live-birth outcomes in patients with RPL in a recent meta-analysis. 104 However, the studies included were inadequately powered, had co-intervention with heparin and aspirin, and had notable heterogeneity in inclusion criteria. 104 It is unclear whether prednisone improves outcomes for patients with RPL.…”

Section: Hematologicmentioning

confidence: 99%

“…104 However, the studies included were inadequately powered, had co-intervention with heparin and aspirin, and had notable heterogeneity in inclusion criteria. 104 It is unclear whether prednisone improves outcomes for patients with RPL. 105 Furthermore, its use is associated with an increased risk of prematurity, gestational diabetes mellitus, and hypertension.…”

Section: Hematologicmentioning

confidence: 99%

Evaluation of Recurrent Pregnancy Loss

de Assis,

Giugni,

Ros

2024

Obstetrics &Amp; Gynecology

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Recurrent pregnancy loss (RPL) affects approximately 5% of couples. Although RPL definitions vary across professional societies, an evaluation after a second clinically recognized first-trimester pregnancy loss is recommended. Good quality evidence links parental chromosomal rearrangements, uterine anomalies, and antiphospholipid syndrome (APS) to RPL. In contrast, the relationship between RPL and other endocrine, hematologic, and immunologic disorders or environmental exposures is less clear. Anticoagulant therapy and low-dose aspirin are recommended for patients with RPL who have also been diagnosed with APS. Vaginal progesterone supplementation may be considered in patients experiencing vaginal bleeding during the first trimester. Surgical correction may be considered for patients with RPL in whom a uterine anomaly is identified. Evaluation and management of additional comorbidities should be guided by the patient's history rather than solely based on the diagnosis of RPL, with the goal of improving overall health to reduce complications in the event of pregnancy. Most people with RPL, including those without identifiable risk factors, are expected to achieve a live birth within 5 years from the initial evaluation. Nevertheless, clinicians should be sensitive to the psychological needs of individuals with this condition and provide compassionate and supportive care across all stages.

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Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

Cited by 8 publications

References 39 publications

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death

Demystifying the impact of prenatal tobacco exposure on the placental immune microenvironment: Avoiding the tragedy of mending the fold after death

Recent Advances in Immunotherapeutic Approaches for Recurrent Reproductive Failure

Evaluation of Recurrent Pregnancy Loss

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