A Unified Pathogenesis of Allergic Diseases; The Protein-Homeostasis-System Hypothesis

The etiology and pathophysiology of allergic diseases remain incompletely understood. Current immunological paradigms, while insightful, often fall short in fully elucidating the mechanisms underlying allergic and autoimmune disorders. Under the protein-homeostasis-system (PHS) hypothesis, allergic diseases have etiological substances, and immune reactions against them are responsible for clinical manifestations of allergic diseases. The etiological substances are mainly external in origin and very small with each biochemical property and react to target cells in various organ tissues. Eosinophils, mast cells, and immunoglobulin Es as major immune effectors in allergic diseases control toxic substances according to the chemical or biochemical properties of these substances. Mast cells in the central nervous system may be associated with allergic episodes through connection to peripheral mast cells, and this connection is proposed as the mast cell-associated network. The toxic and/or bioactive proteins/peptides and other non-protein substances, which are derived from injured cells caused by allergic reactions, induce activation of adaptive and innate immune components for controlling the substances. New insights into the etiology and pathophysiology of allergic diseases are introduced with the PHS hypothesis.