Sepsis and Apolipoprotein H in Pediatric Patients

Sepsis, characterized by dysregulation of the body's response to infection, stands as the main cause of mortality in children. Despite the numerous clinical trials conducted, the quest for effective drugs to combat sepsis remains an immensely challenging undertaking.

Apolipoprotein H (APOH), also known as beta-2-glycoprotein I (β2-GPI), is a highly abundant plasma protein with a molecular size of approximately 50 kDa. It is primarily synthesized by liver cells and comprises five domains (I–V). It is a critical plasma protein that plays a crucial role in regulating various biological processes. However, its precise role in the immunopathology of pediatric sepsis remains unclear.

Recent Research Findings

A recent research paper investigates the potential role of Apolipoprotein H (APOH) in pediatric sepsis. The study evaluated the concentration of APOH in pediatric patients with sepsis and healthy individuals, and the impact of APOH on survival, organ injury, and inflammation in a clinically relevant sepsis model induced by caecal ligation and puncture (CLP).

• The findings indicated that APOH levels were decreased in patients with sepsis compared to healthy controls, and lower APOH levels were associated with higher mortality rates.
• Therapeutic intervention with recombinant APOH protein lowered the mortality rate, mitigated organ injury, and suppressed inflammation in mice with severe sepsis.
• Neutralizing APOH with an anti-APOH monoclonal antibody increased the mortality rate and exacerbated organ injury.
• APOH inhibited M1 polarization in macrophages by suppressing the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) signaling pathway, without directly affecting bacterial burden, neutrophil, and macrophage counts.

The authors concluded that APOH has a protective role in the host defense response to sepsis and highlighted its potential therapeutic value in sepsis treatment. This study provides valuable insights into the potential role of APOH in modulating the immunopathology of pediatric sepsis and the underlying molecular mechanisms.

Reference

Yu, Z., Xiao, C., Liu, R. et al. The protective effect of apolipoprotein H in pediatric sepsis. Crit Care 28, 36 (2024). https://doi.org/10.1186/s13054-024-04809-2