Abnormal extracellular protein at sites of inflammation

Abnormal extracellular proteins at sites of inflammation is a broad, descriptive term used to categorize various proteinaceous molecules that undergo structural or chemical changes during inflammatory responses. This group includes misfolded proteins, damage-associated molecular patterns (DAMPs) like HMGB1, and neo-epitopes generated from the proteolytic degradation of the extracellular matrix (ECM) (Bianchi, M. E., J Leukoc Biol 2007). These proteins are typically absent or sequestered in healthy tissue but become prominent in the extracellular space during infection, autoimmune flare-ups, or tissue necrosis. They play a critical role in disease progression by acting as ligands for pattern recognition receptors (PRRs), thereby amplifying the inflammatory cascade (Seong & Matzinger, Nat Rev Immunol 2004). In the context of drug development, these proteins serve as specific markers for diagnostic imaging (e.g., using radiolabeled antibodies or peptides) and as targets for therapeutic intervention aimed at neutralizing pro-inflammatory signals. Targeting these abnormal proteins allows for localized treatment of conditions such as rheumatoid arthritis, atherosclerosis, and myocardial infarction, potentially reducing systemic side effects associated with traditional anti-inflammatory therapies.

Other names

Extracellular matrix neo-epitopesMisfolded proteinsDamage-associated molecular patternsDAMPsModified extracellular proteinsNecrotic debris

Binding to exposed epitopes or modified residues (e.g., citrullination, oxidation) that are typically sequestered or absent in healthy tissue, allowing for localized imaging or therapeutic intervention (Szekanecz et al., Nat Rev Rheumatol 2010).