Inflammatory Burden–Driven Bistability of Maternal–Fetal Immune Tolerance: A Framework for Pregnancy Complications

Maternal–fetal immune tolerance requires controlled immune quiescence toward the semi‑allogeneic fetus while preserving host defense. However, a static immunosuppression model does not fully explain key clinical phenomena, including heterogeneous pregnancy outcomes, abrupt onset of preeclampsia, and transient postpartum autoimmune activation. We propose a bistable dynamical framework in which maternal–fetal immunity operates between two attractor states: a tolerance state and an inflammation state. State transitions are governed by an integrated inflammatory burden (I), representing cumulative effects of hypoxia, tissue damage, infection, and mechanical stress. A forward threshold (T_f) triggers transition to inflammation, whereas a lower reverse threshold (T_r) governs recovery, generating hysteresis and a postpartum vulnerability window. Within this framework, recurrent miscarriage reflects elevated baseline inflammatory burden, preeclampsia results from acute threshold crossing, preterm birth from sustained inflammatory drive, and postpartum autoimmunity from delayed reverse transition. A composite peripheral immune index (PI = (Treg% × IL‑10)/(IL‑6 × sCD25)) is proposed as a potential translational readout pending validation.