title: C-Terminal Alpha-1 Antitrypsin Peptide: A New Sepsis Biomarker with Immunomodulatory Function.
abstract: 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.
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Blaurock
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Schmerler
authors.affiliation: Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Albert-Einstein-Street 10, 07745 Jena, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Hünniger
authors.affiliation: Septomics Research Center, Friedrich Schiller University and Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute (HKI), Albert-Einstein-Street 10, 07745 Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany; Department of Anesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Ludewig
authors.affiliation: Department for Medical Microbiology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Baier
authors.affiliation: Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany; Department of Anesthesiology and Intensive Care, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany; Paul-Martini-Research Group, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Frank Martin
authors.initials: FM
authors.lastname: Brunkhorst
authors.affiliation: Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, Brühler Street 7, 53119 Bonn, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Imhof
authors.affiliation: Department of Clinical Chemistry and Laboratory Medicine, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany; Center for Sepsis Control and Care (CSCC), Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Kiehntopf
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000515:alpha 1-Antitrypsin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D007155:Immunologic Factors; D010455:Peptides; D000515:alpha 1-Antitrypsin