Coupled Epigenetic, Mechanical, Network, and Intestinal Attractors as a Threshold Mechanism for Chronicity in Gut-Driven Axial Spondyloarthritis: A Hypothesis

Abstract

* Chronic gut-driven axial spondyloarthritis is hypothesized to persist through a coupled four-node systems architecture rather than a single dominant inflammatory pathway. * Four interacting persistence nodes are proposed: epigenetic memory (N1), extracellular matrix stiffening (N2), adaptive inter-enthesis network (N3), and gut immune interface (N4). * Two threshold modifiers (M1 and M2) are introduced as regulators of attractor stability and transitions between chronic and remission states. * Four remission thresholds (R1–R4) are proposed as the conditions required for durable disease resolution rather than transient cytokine suppression. * The framework generates biomarker-based, experimentally falsifiable predictions that can be evaluated using existing longitudinal biobanked cohorts and archived biological samples without requiring new patient recruitment.