No Recognition Error: A Matrix of Forty-Nine Immune-Mediated Diseases Read Through Seven Modalities of Antigenic Homeostasis Disturbance

Background. More than one hundred chronic non-communicable diseases are classified as autoimmune. The prefix carriesan explanation: that the immune system has ceased to recognise what belongs to the organism and attacks it in error. Thisexplanation was coined before the mechanisms were known.Objective. To test whether the error is required. For each of a defined set of immune-mediated diseases, the question askedis not whether recognition failed, but whether a documented event made a structure visible that the repertoire had neverbeen educated on.Methods. Seven modalities by which an antigen can become visible were defined operationally: release (REL), defectiveclearance (CLR), anomalous localisation (LOC), molecular modification (MOD), anomalous processing (PRC),anomalous presentation (MHC) and persistence (PER). Diseases entered the matrix only if three conditions were met: theantigen is identified; the mechanism that exposes it is documented; and, where the disease is chronic, the mechanism thatmaintains the exposure is documented. Each filled cell cites published primary literature. A removal proof was recordedwhere documentation exists that withdrawing an identified substance arrests, reverses or prevents the disease.Results. Forty-nine diseases met the admission criterion, yielding 112 documented intersections. Modality frequencieswere MOD 30, PER 29, REL 20, LOC 14, MHC 10, PRC 7 and CLR 2. Diseases grouped by number of modalities as 5with one, 29 with two, 14 with three and one — systemic lupus erythematosus — with all seven; no disease exhibited four,five or six. Sixteen diseases carry a removal proof. Five resolve spontaneously when an external event ends. In none of the112 intersections was it necessary to postulate recognition of something that was not present.Conclusions. Across this set, the recognition error is not required as an explanatory term. The two most populatedcolumns describe chemistry and time, in neither of which the immune system appears as an agent. The distribution ofmodalities tracks the ease of measurement rather than biological frequency, which yields a research programme bysubtraction: for each modality, the measurement that would document it in the diseases where it has not been sought. Fourfalsification tests are stated in advance.Fifth in a series on the AHDI hypothesis (Antigenic Homeostasis Driven Immunopathology).