An admission framework for antigen-driven chronic disease: three classes, four evidence levels and six critical instruments, applied to eleven common conditions

Hypotheses that attribute a role to adaptive immunity in common chronicdiseases are easy to formulate and hard to refute, because the conditions inquestion are inflammatory, because lymphocytes are present in the affectedtissue, and because antibodies against self constituents can be detected in aproportion of patients. None of these observations discriminates between animmune response that maintains the disease and one that merelyaccompanies it. This article proposes an admission framework designed tomake that discrimination explicit and, where the evidence is insufficient, tomake the insufficiency visible.The framework has four components. First, a closed list of seven tissue-levelevents that can render endogenous material persistently accessible orpersistently immunogenic. Second, a three-class admission rule with nointermediate grades. Third, a four-level hierarchy of antigen-specific evidencein which the species in which each observation was made must be declaredon the same line as the observation. Fourth, a set of six critical instrumentsapplied symmetrically to the dominant explanation of each disease and to theproposed one.The framework was applied to eleven common conditions. No conditionreached the highest class. Eight were admitted as candidates with a specifiedmissing requirement; three were declared outside the scope of the model;one required a class that the original rule had not foreseen, because the siteat which the antigenic anomaly is generated and the site at which diseasemanifests are different organs. The resulting table is offered as the principaloutput: its empty cells are the part of the exercise that carries information.