C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function

Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim o...

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Bibliographic Details
Published in:Mediators of inflammation 2016-01, Vol.2016 (2016), p.1-13
Main Authors: Kiehntopf, Michael, Imhof, Diana, Baier, Michael, Ludewig, Katrin, Kurzai, Oliver, Hünniger, Kerstin, Schmerler, Diana, Blaurock, Nancy, Brunkhorst, Frank Martin
Format: Article
Language:English
Subjects:
Aged
Alpha 1-antitrypsin
alpha 1-Antitrypsin - chemistry
alpha 1-Antitrypsin - genetics
alpha 1-Antitrypsin - metabolism
Apoptosis
Apoptosis - drug effects
Biological markers
Biomarkers
Biomarkers - chemistry
Biomarkers - metabolism
Cell Survival - drug effects
Cells, Cultured
Colleges & universities
Cytokines
Cytokines - metabolism
Female
Flow Cytometry
Heart surgery
Humans
Immunologic Factors - chemistry
Immunologic Factors - genetics
Immunologic Factors - pharmacology
Infections
Male
Middle Aged
Mortality
Neutrophils
Neutrophils - drug effects
Peptides
Peptides - chemistry
Peptides - genetics
Peptides - pharmacology
Pharmaceuticals
Physiological aspects
Polymorphism, Single Nucleotide - genetics
Sepsis
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Description
Summary:Systemic inflammatory response syndrome (SIRS) is a life threatening condition and the leading cause of death in intensive care units. Although single aspects of pathophysiology have been described in detail, numerous unknown mediators contribute to the progression of this complex disease. The aim of this study was to elucidate the pathophysiological role of CAAP48, a C-terminal alpha-1 antitrypsin fragment, that we found to be elevated in septic patients and to apply this peptide as diagnostic marker for infectious and noninfectious etiologies of SIRS. Incubation of human polymorphonuclear neutrophils with synthetic CAAP48, the SNP-variant CAAP47, and several control peptides revealed intense neutrophil activation, induction of neutrophil chemotaxis, reduction of neutrophil viability, and release of cytokines. We determined the abundance of CAAP48 in patients with severe sepsis, severe SIRS of noninfectious origin, and viral infection. CAAP48 levels were 3-4-fold higher in patients with sepsis compared to SIRS of noninfectious origin and allowed discrimination of those patients with high sensitivity and specificity. Our results suggest that CAAP48 is a promising discriminatory sepsis biomarker with immunomodulatory functions, particularly on human neutrophils, supporting its important role in the host response and pathophysiology of sepsis.
ISSN:0962-9351
1466-1861
DOI:10.1155/2016/6129437