Chromogranin A and Its Fragments in the Critically Ill: An Expanding Domain of Interest for Better Care

Abstract

Life-threatening diseases challenge immunity with a release of chromogranins. This report focuses on Chromogranin A (CGA) and some of its derived peptides in critically ill patients, with attention paid to their potential to become biomarkers of severity and actors of defense. First, we studied whether circulating CGA may be a biomarker of outcome in non-selected critically ill patients: CGA concentrations were reliably associated with short-term death, systemic inflammation, and multiple organ failure. Additionally, when studying Vasostatin-I, the major N-terminal fragment of CGA, we noted its reliable prognostic value as early as admission if associated with age and lactate. In trauma patients, CGA concentrations heralded the occurrence of care-related infections. This was associated with an in vitro inhibitor impact of Chromofungin on both NF-kappa B- and API-transcriptional activities. Secondly, in life-threatening disease-induced oxidative stress, the multimerization of Vasostatin-I occurs with the loss of its anti-microbial properties ex vivo. In vivo, a 4%-concentration of non-oxidized albumin infusion reversed multimerization with a decrease in care-related infections. Finally, in vitro Catestatin impacted the polymorphonuclear cells-Ca++-dependent, calmodulin–regulated iPLA2 pathway by releasing immunity-related proteins. Furthermore, human Cateslytin, the active domain of Catestatin, helped destroy S. aureus: this prompted the creation of synthetic D-stereoisomer of CGA-derived peptides against superbugs for the protection of implanted devices. In conclusion, CGA consideration in the critically ill is only starting, but it offers interesting perspectives for improved outcomes.

The Editorial Position on ‘Recent Advances in Multifunctional Antimicrobial Peptides as Preclinical Therapeutic Studies and Clinical Future Applications’

“…Also, for trauma patients, CgA levels can predict the onset of nosocomial infections, and their CgA-derived peptides can act as inhibitors of inflammation and antimicrobial peptides. Finally, they also demonstrated that a 4% concentration of non-oxidized albumin infusion reverses the multimerization of these peptides, restoring their anti-inflammatory and antimicrobial properties [4]. They concluded that CgA and its peptides could be considered relevant biomarkers in critically ill patients.…”

“…One of the significant aspects of Dr. Metz-Boutigue's remarkable success has been her collaborative spirit, as she has fostered partnerships with brilliant researchers worldwide. Among her notable collaborators are Prof. Schneider, renowned for his expertise in intensive care medicine and infection, and together they discovered the role of several AMPs as biomarkers in critically ill patients [4]; Dr. Prévost, an expert in microbiology, who, together with Dr. Metz-Boutigue, identified new AMPs against resistant S. aureus strains [5]; and Dr. Goumon, an expert in neuroscience, with whom Dr. Metz-Boutigue discovered several AMPs derived from the neuroendocrine system [6]. Of note are her collaborations with Dr.…”

“…Another important application for MF-AMPs in human health is their roles as the biomarkers of several diseases both related and unrelated to infections [28][29][30][31]. In this Special Issue, Scnheider and collaborators summarized the biomarker profile of CgA and its derived antimicrobial peptides in the context of critically ill patients [4]. They reported the role of CgA as a biomarker of outcome in non-selected critically ill patients.…”