Quantitative analysis of murine C-terminal alpha-1-antitrypsin peptides in experimental sepsis and their comparison with human sepsis peptide biomarkers.

CONTEXT: The levels of alpha-1-antitrypsin (AAT) peptides could be used as prognostic biomarkers in critically ill patients, and peptide treatment has therapeutic efficiency in experimental sepsis. However, the regulation of AAT peptides in M. musculus is unknown, although they may be prerequisites for peptide-based therapies. This study aims to quantify murine AAT peptides and investigate their regulation during experimental sepsis.

METHODS

LC-MS/MS was used to quantify six AAT peptides from two murine AAT isoforms in plasma of septic mice.

RESULTS

Peptide mC36-2 is the most abundant and significantly regulated murine AAT peptide, with approximately 20-fold higher level than in critically ill patients. In contrast, the upregulation of peptide C42 in septic patients is absent in mice; thus, it may represent a specific marker of human disease. Nevertheless, the increase and kinetics of mC36 during experimental sepsis reflect our observations in patients.

CONCLUSIONS

In summary, the conserved upregulation of AAT peptides reflects important pathophysiological mechanisms of severe infections; thus, peptide levels can be used as predictive biomarkers in experimental and clinical sepsis. Although species-specific differences exist and need to be considered, quantification of AAT peptides might help to characterize individual immune responses and build the foundation for novel therapeutic approaches in pre-clinical and clinical research.