Soluble Mediators Related to Immunity in Pregnancy-Related Disorders: Roles of Immune Checkpoints, Platelet Activation Markers, TNF Receptors, and NETs

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This paper reviews soluble immune mediators in pregnancy-related disorders, focusing on soluble immune checkpoints, soluble platelet activation markers, soluble TNF receptors, and neutrophil extracellular traps (NETs), which are released into peripheral blood via alternative splicing or proteolytic shedding. It describes how these factors help regulate immune tolerance, vascular remodeling, and inflammation at the maternal–fetal interface, and it summarizes associations reported between altered levels of these mediators and complications such as recurrent miscarriage, preeclampsia, and endometriosis. A stated limitation is that the discussion is conceptual and based on previously published findings rather than new datasets generated or analyzed by the authors (no primary experiments are reported). Relevance to endometriosis: the abstract explicitly links altered soluble immune mediators with endometriosis and notes that examining their dynamics during pregnancy may inform immune-mediated reproductive disorders, though the paper’s main focus is a broad review of soluble immune mediators rather than endometriosis alone.

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Abstract

Soluble immune mediators are key regulators of immune responses that help maintain self-tolerance and prevent autoimmunity. Recently, many forms of these mediators have been found, including soluble immune checkpoints, soluble platelet activation markers, soluble tumor necrosis factor receptors, and neutrophil extracellular traps (NETs). These factors are released into peripheral blood circulation via alternative splicing or proteolytic shedding, preserving the immunological functions of their membrane-bound isoforms. They are crucial in regulating immune tolerance, vascular remodeling, and inflammation at the maternal-fetal interface throughout pregnancy. Alterations in the levels of these mediators are linked to pregnancy complications, including recurrent miscarriage, preeclampsia, and endometriosis. Examining the dynamics of these molecules during pregnancy could provide significant insights regarding their potential as biomarkers or therapeutic targets for immune-mediated reproductive disorders.
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Soluble Mediators Related to Immunity in Pregnancy-Related Disorders: Roles of Immune Checkpoints, Platelet Activation Markers, TNF Receptors, and NETs Forough Parhizkar Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorNajibeh Shekari Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorZahra Parhizkar School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorAli Aghebati-Maleki Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Molecular Medicine, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorArman Rostamlou Department of Medical Biology, Faculty of Medicine, University of EGE, Izmir, Turkey Search for more papers by this authorCorresponding Author Leili Aghebati-Maleki Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorForough Parhizkar Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorNajibeh Shekari Department of Immunology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorZahra Parhizkar School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran Search for more papers by this authorAli Aghebati-Maleki Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Department of Molecular Medicine, School of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorArman Rostamlou Department of Medical Biology, Faculty of Medicine, University of EGE, Izmir, Turkey Search for more papers by this authorCorresponding Author Leili Aghebati-Maleki Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Search for more papers by this authorABSTRACT Soluble immune mediators are key regulators of immune responses that help maintain self-tolerance and prevent autoimmunity. Recently, many forms of these mediators have been found, including soluble immune checkpoints, soluble platelet activation markers, soluble tumor necrosis factor receptors, and neutrophil extracellular traps (NETs). These factors are released into peripheral blood circulation via alternative splicing or proteolytic shedding, preserving the immunological functions of their membrane-bound isoforms. They are crucial in regulating immune tolerance, vascular remodeling, and inflammation at the maternal–fetal interface throughout pregnancy. Alterations in the levels of these mediators are linked to pregnancy complications, including recurrent miscarriage, preeclampsia, and endometriosis. Examining the dynamics of these molecules during pregnancy could provide significant insights regarding their potential as biomarkers or therapeutic targets for immune-mediated reproductive disorders. Conflicts of Interest The authors declare that they have no conflicts of interest. 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Tàssies, J. C. Reverter, et al., “Circulating Neutrophil Extracellular Traps Are Elevated in Patients With Deep Infiltrating Endometriosis,” Reproductive Sciences 26, no. 1 (2019): 70–76. - 111H. Li, L. Liu, J. Wang, and W. Zhao, “The Emerging Role of Neutrophil Extracellular Traps in Endometritis,” Frontiers in Immunology 14 (2023): 1153851. - 112M. Meggyes, E. Miko, A. Lajko, et al., “Involvement of the PD-1/PD-L1 Co-Inhibitory Pathway in the Pathogenesis of the Inflammatory Stage of Early-Onset Preeclampsia,” International Journal of Molecular Sciences 20, no. 3 (2019): 583. Article Metrics Total unique accesses to an article’s full text in HTML or PDF/ePDF format.More metric information Scite metrics Explore this article's citation statements on scite.ai Share QR Code Generating QR code QR code copied to clipboard! Something went wrong while generating your QR code. Please try again in a moment. If the issue persists, refresh the page or contact support. 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endometriosis

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Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Abortion, Habitual Endometriosis Endometriosis Endometriosis

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