Polyethoxylated Pattern Mimicry as a Candidate Amplifier of Tissue-Specific Autoimmunity

Version note Version 3.0 supersedes and substantially revises the earlier preprint "Hidden Origins of Modern Autoimmunity" (DOI: 10.5281/zenodo.19486877). The argument is restructured around a disciplined, falsifiable application of polyethoxylated pattern mimicry, now explicitly distinguished (§1.1) from transport-based mechanisms proposed elsewhere in this research program (VECT; Microbial-Excipient Synergy). Multiple sclerosis is introduced as a worked example (§8) that specifies the model's five required parameters — tissue, barrier, access pathway, trigger, and phenotype — and yields three falsifiable predictions (§8.1) together with explicit falsification criteria (§8.2), built around a combined HHV-6/EBV reactivation signature rather than either virus alone. Claims regarding the Vojdani & Vojdani (2025) in vitro cross-reactivity data have been recalibrated throughout to avoid overstating their relevance to naturally occurring human antibodies or in vivo autoimmunity, and the Epistemic Status statement now flags that this evidence and the HHV-6/EBV signature derive from overlapping research groups, requiring independent replication. Abstract This work introduces polyethoxylated pattern mimicry as a hypothesis-generating framework for innate immune amplification under conditions of tissue damage. We propose that anti-PEG/anti-polysorbate antibodies may, in restricted inflammatory contexts, recognize exposed repetitive endogenous structures and amplify complement-mediated tissue injury. This mechanism is distinct from excipient-mediated transport models such as VECT: it addresses recognition of already exposed structures, not barrier access. The framework is supported by evidence for prevalent anti-PEG antibodies, complement activation by PEG-containing systems, and in vitro cross-reactivity of experimentally generated anti-PEG antibodies with selected human autoantigens. However, its extension to naturally occurring human anti-PEG/PS80 antibodies as in vivo initiators of autoimmunity remains untested. As a worked example, we restrict the model to clinically isolated demyelinating syndrome occurring within a defined window of combined HHV-6/EBV reactivation, where elevated functional anti-PEG/PS80 IgM activity and myelin-antigen reactivity would constitute falsifiable predictions.