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

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.