High mobility group box 1 (HMGB1) is a non-histone nuclear protein involved in DNA organization, transcription regulation, and cellular stress responses. Structurally, it contains two DNA-binding domains (A and B boxes) and a C-terminal acidic tail. Under physiological conditions, HMGB1 localizes to the nucleus, stabilizing nucleosome structure and facilitating DNA repair. However, during cellular stress, necrosis, or inflammation, HMGB1 can be actively secreted by immune cells or passively released from damaged cells, functioning as a damage-associated molecular pattern (DAMP) molecule. Extracellular HMGB1 interacts with receptors like TLR4 and RAGE, triggering pro-inflammatory cytokine production and promoting pathological processes such as sepsis, autoimmune diseases, and cancer progression.
HMGB1 antibodies are critical tools for studying its dual roles in homeostasis and disease. They enable detection of HMGB1 localization (nuclear vs. cytoplasmic/extracellular) via techniques like Western blot, immunohistochemistry, and immunofluorescence. Neutralizing antibodies targeting HMGB1 have shown therapeutic potential in preclinical models by blocking its interaction with inflammatory receptors, thereby attenuating conditions like rheumatoid arthritis, ischemia-reperfusion injury, and sepsis. However, challenges remain in clinical translation due to HMGB1's context-dependent functions—while inhibiting HMGB1 may reduce inflammation, it could also interfere with its tissue-repair roles. Recent research explores isoform-specific antibodies and post-translational modification-targeted approaches to refine therapeutic strategies, reflecting growing interest in HMGB1 as a biomarker and therapeutic target in inflammatory and degenerative diseases.