Damage-associated molecular pattern and self-antigen (DAMP)

Damage-associated molecular patterns (DAMPs) and self-antigens are endogenous molecules that serve as signals of cellular stress, damage, or non-programmed cell death, triggering innate and adaptive immune responses (Roh & Sohn, 2018). DAMPs, such as high mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins, are released into the extracellular space where they interact with pattern recognition receptors (PRRs) like Toll-like receptors (TLRs) and the receptor for advanced glycation end-products (RAGE) (Gong et al., 2020). This interaction initiates sterile inflammation, which is crucial for tissue repair but can lead to chronic inflammatory diseases, sepsis, and cancer when dysregulated (Zindel & Kubes, 2020). Self-antigens are typically normal cellular components that become targets of the adaptive immune system in autoimmune disorders, such as myelin basic protein in multiple sclerosis or insulin in type 1 diabetes (Janeway et al., 2001). Therapeutic interventions targeting this category include monoclonal antibodies designed to neutralize specific DAMPs or small molecules that block their receptors to dampen pathological inflammation (Venereau et al., 2015). However, because many DAMPs have essential intracellular functions, therapeutic targeting requires precision to avoid interfering with normal physiological processes and wound healing (Harris et al., 2012).

Other names

AlarminEndogenous danger signalAutoantigenCell-death-associated molecular patternEndogenous ligand

Neutralization of endogenous ligands or blockade of pattern recognition receptors (PRRs) to inhibit downstream inflammatory signaling pathways (Venereau et al., 2015).