The Self-amplifying Inflammatory Cascade in Obstetric Antiphospholipid Syndrome: From Pathophysiology to Placenta-centric Immunotherapeutic Targets

Obstetric Antiphospholipid Syndrome (OAPS) is an autoimmune-driven pregnancy complication whose core pathology is a dysregulated inflammatory cascade at the maternal-fetal interface, rather than the traditionally emphasized thrombosis. Antiphospholipid antibodies (aPL) trigger a diverse array of innate immune pathways, including the complement system, neutrophils, and the inflammasome, leading to trophoblast dysfunction, poor placentation, and ultimately, adverse pregnancy outcomes such as recurrent miscarriage, preeclampsia, and fetal growth restriction. The current standard of care, low-dose aspirin combined with heparin, primarily targets coagulation and has limited efficacy in controlling the underlying inflammatory response, resulting in treatment failure in approximately 20–30% of patients. This review aims to redefine the inflammatory nature of OAPS, elaborate on the immune-pathological network centered on the placenta, and critically examine the pivotal role of the signaling cascade mediated by TLR4 that activates the downstream NF-κB transcription factor as a major regulatory node of the inflammatory response. In this context, experimental inhibitors target the initiation of this cascade at the receptor level to prevent the subsequent nuclear translocation of NF-κB. Building on this, we review the evolution of treatment strategies from traditional anticoagulants to immunosuppressants and propose that “targeting the local placental immune microenvironment” is the core direction for future therapies. Finally, this paper discusses a novel snail-inspired bioactive substance, specifically focusing on the natural glycosaminoglycan AFG (Achatina fulica glycosaminoglycan). This glycosaminoglycan is a non-anticoagulant heparin-like GAG purified from snail mucus, characterized by a regular repeating sequence of →4)-β-D-GlcNAc(1→4)-α-L-IdoA2S(1→. AFG functions as a specialized immunomodulator that stabilizes placental cellular signaling by precisely targeting the placental inflammatory axis.