Plasma concentrations and importance of high mobility group box protein in the prognosis of organ failure in patients with disseminated intravascular coagulation

Abstract

High Mobility Group Box chromosomal protein 1 (HMGB1) is a nuclear DNA-binding protein acting as a proinflammatory cytokine when released in the extracellular space from necrotic cells,activated macrophages and dendritic cells. HMGB1 acts on a specific receptor, RAGE (receptor for advanced glycation end-products), and induces prolonged inflammation, organ failure, septicaemia and death. The aim of the study was to determine the diagnostic value of plasma HMGB1 concentration and its role in the development of organ failure in patients with disseminated intravascular coagulation (DIC). Plasma HMGB-1 levels were measured in patients with suspected DIC and their relationships with DIC, organ failure and clinical outcome were determined. The study took place at the intensive care facility, Mie University School of Medicine and comprised 201 patients with suspected DIC. Plasma HMGB1 was below the detection limit in normal subjects, but moderately elevated in patients with infectious diseases (4.54 +/- 8.18 ng/ml, mean +/- SD), malignancies (2.15 +/- 5.34 ng/ml),and traumas (6.47 +/- 13.13 ng/ml). DIC was associated with significantly high plasma HMGB1 (14.05 +/- 12.56 ng/ml) in these patients. The highest HMGB1 levels were in patients with organ failure (8.29 +/- 10.99 ng/ml) and non-survivors (16.58 +/- 11.01 ng/ml). HMGB1 plasma levels correlated with the DIC score and sepsis-related organ failure assessment (SOFA) score. In conclusion, our data suggest that HMGB-1 is a potentially suitable prognostic marker of OF or DIC.

Clinical Significance of Serum HMGB-1 and sRAGE Levels in Systemic Sclerosis: Association with Disease Severity

“…In this study, serum HMGB-1 and sRAGE levels correlated with various [8,[17][18][19][20][21][22]. HMGB-1 is actively secreted by damaged, necrotic, and apoptotic cells after translocation from the nucleus to secretory lysosomes [5,6].…”

“…HMGB-1 and RAGE are known to be causally involved in a variety of pathophysiological processes, such as rheumatoid arthritis, acute lung injury, disseminated intravascular coagulation, Alzheimer disease, tumorigenesis, abnormalities associated with diabetes, and impaired wound healing [8,[17][18][19][20][21][22]. Although HMGB-1 is regarded as a trigger of these immune/inflammatory disorders mediated via RAGE and TLR and also affects immunological abnormalities [5,6,9,12,23], correlation of serum…”

“…Recently, increasing serum HMGB-1 levels have been reported in several immune/inflammatory disorders [8,[17][18][19][20][21][22]. However, it has been controversial whether sRAGE increases or decreases in immune/inflammatory conditions.…”

Chaperone-like Activity of High-Mobility Group Box 1 Protein and Its Role in Reducing the Formation of Polyglutamine Aggregates

“…HMGB1 binds to TLR-2, -4, and receptor for advanced glycation end products (5,6) and promotes inflammation. HMGB1 was also shown to act as a late mediator of endotoxemia and sepsis in animal models and human patients (7)(8)(9)(10). HMGB1 moves to the cytoplasm via a redox-dependent mechanism and plays a role as a regulator between macroautophagy and apoptosis in the cytoplasm by binding to beclin-1 and dissociating from bcl-2 (11).…”

High-Mobility Group Box-1 Protein (HMGB1) Is Increased in Antineutrophilic Cytoplasmatic Antibody (ANCA)-Associated Vasculitis with Renal Manifestations

“…Targeting HMGB1 has been demonstrated to confer protection in animal models of sepsis, endotoxemia and arthritis (10,20,21). Elevated HMGB1 levels in serum have been documented in clinical inflammatory conditions such as sepsis and rheumatoid arthritis (RA) as well as chronic kidney disease (22)(23)(24)(25).…”