Role Of Haptoglobin Binding Proteins In Influencing Immune Response In Sepsis

Abstract

Sepsis is a life-threatening condition characterized by a dysregulated immune response to infection, leading to widespread inflammation and organ dysfunction. Haptoglobin (Hp), an acute-phase protein, plays a critical role in mitigating oxidative damage by binding free hemoglobin. This study investigated the interaction partners of haptoglobin in serum samples from healthy individuals, sepsis survivors, and non-survivors using immunoprecipitation and mass spectrometry. Distinct protein profiles were identified across the three groups, highlighting the role of haptoglobin-binding proteins in immune regulation, inflammation, and cellular stress responses. In healthy individuals, haptoglobin primarily interacted with proteins involved in maintaining cellular integrity and vascular permeability. Sepsis survivors exhibited interactions with proteins regulating inflammatory gene expression, oxidative stress, and tissue repair, suggesting a controlled immune response. In contrast, non-survivors showed associations with proteins linked to dysregulated apoptosis, antibiotic resistance, and hyperinflammation, indicative of poor outcomes. Key proteins such as MORF4 family-associated protein 1 (in survivors) and CASP8 and FADD-like apoptosis regulator (in non-survivors) were identified as potential biomarkers and therapeutic targets. These findings underscore the importance of haptoglobin and its binding partners and suggest that targeting these proteins could provide valuable insights into sepsis pathophysiology. Further research is needed to validate these proteins as biomarkers and explore their therapeutic potential in sepsis management.