title: Identification of CD177 as the most dysregulated parameter in a microarray study of purified neutrophils from septic shock patients.
abstract: Sepsis represents the host's systemic inflammatory response to an infection. In this condition, immune response associates a marked inflammatory response and the delayed development of severe dysfunctions affecting both innate and adaptive responses. As neutrophils are the first line of defense against infection, they are central to the pathophysiology of sepsis in first hours. Nevertheless, their role during immunosuppression phase remains elusive. The main objective of the current work was to perform a transcriptomic study on purified neutrophils from septic shock patients (n=9) so as to identify genes that are differentially expressed during the first week after disease onset both (3-4 and 6-8days) versus healthy donors. Then, 45 septic shock patients were prospectively enrolled to confirm results at the protein level using flow cytometry. Twenty healthy volunteers (HV) were also included for the whole study. By comparing the transcriptome of purified neutrophils, we identified 364 up-regulated and 328 down-regulated genes differentially expressed. Of them, CD177 mRNA, coding for an activation molecule in chemotaxis, had the highest fold change modulation between patients and HV. This increase was then confirmed at the protein level. There was a constant subset of neutrophils that did not express CD177. However, when positive, septic neutrophils presented with significantly increased CD177 expression. Of note, no association between CD177 overexpression and features of immunosuppression has been highlighted. In addition, this up-regulation was negatively correlated with a decreased expression of CD10, a characteristic of immature myeloid cells. In conclusion, in this exploratory work, we shed light on the increased CD177 mRNA and protein expressions in circulating neutrophils after septic shock. Considering the potential dual roles of CD177 neutrophil (i.e., maturation/chemotaxis), negatively correlated in this study, its participation in septic shock pathophysiology deserves further investigation. Furthermore, its potential as a biomarker for sepsis would deserve to be investigated in large cohorts of patients.
authors: Hospices Civils de Lyon, Immunology Laboratory, E. Herriot Hospital, Lyon, 69003, France; EA 7426, Pathophysiology of injury-induced immunosuppression, University Claude Bernard Lyon 1, BioMérieux Hospices Civils de Lyon, E. Herriot Hospital, Lyon, 69003, France. Electronic address: julie.demaret@chu-lyon.fr.
authors: Julie
authors: J
authors: Demaret
authors: Hospices Civils de Lyon, Immunology Laboratory, E. Herriot Hospital, Lyon, 69003, France; EA 7426, Pathophysiology of injury-induced immunosuppression, University Claude Bernard Lyon 1, BioMérieux Hospices Civils de Lyon, E. Herriot Hospital, Lyon, 69003, France. Electronic address: fabienne.venet@chu-lyon.fr.
authors: Fabienne
authors: F
authors: Venet
authors: Hospices Civils de Lyon-bioMérieux Joint Research Unit, E. Herriot Hospital, Lyon, 69003, France. Electronic address: jonathan.plassais@gmail.com.
authors: Jonathan
authors: J
authors: Plassais
authors: Hospices Civils de Lyon-bioMérieux Joint Research Unit, E. Herriot Hospital, Lyon, 69003, France. Electronic address: marie-angelique.cazalis@biomerieux.com.
authors: Marie-Angélique
authors: MA
authors: Cazalis
authors: Hospices Civils de Lyon, Intensive Care Units, Lyon-Sud Hospital, Pierre-Bénite, 69310, France. Electronic address: helene.vallin@chu-lyon.fr.
authors: Hélène
authors: H
authors: Vallin
authors: Hospices Civils de Lyon, Intensive Care Units, Lyon-Sud Hospital, Pierre-Bénite, 69310, France. Electronic address: arnaud.friggeri@chu-lyon.fr.
authors: Arnaud
authors: A
authors: Friggeri
authors: Hospices Civils de Lyon, Intensive Care Units, Lyon-Sud Hospital, Pierre-Bénite, 69310, France. Electronic address: alain.lepape@chu-lyon.fr.
authors: Alain
authors: A
authors: Lepape
authors: Hospices Civils de Lyon, Intensive Care Units, E. Herriot Hospital, Lyon, 69003, France. Electronic address: thomas.rimmele@chu-lyon.fr.
authors: Thomas
authors: T
authors: Rimmelé
authors: Hospices Civils de Lyon-bioMérieux Joint Research Unit, E. Herriot Hospital, Lyon, 69003, France; Hospices Civils de Lyon, Intensive Care Units, E. Herriot Hospital, Lyon, 69003, France. Electronic address: julien.textoris@biomerieux.com.
authors: Julien
authors: J
authors: Textoris
authors: Hospices Civils de Lyon, Immunology Laboratory, E. Herriot Hospital, Lyon, 69003, France; EA 7426, Pathophysiology of injury-induced immunosuppression, University Claude Bernard Lyon 1, BioMérieux Hospices Civils de Lyon, E. Herriot Hospital, Lyon, 69003, France. Electronic address: guillaume.monneret@chu-lyon.fr.
authors: Guillaume
authors: G
authors: Monneret
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D016130:Immunophenotyping; D007519:Isoantigens / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012772:Shock, Septic / Q000175:diagnosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; C407242:CD177 protein, human; D058851:GPI-Linked Proteins; D007519:Isoantigens; D012333:RNA, Messenger; D011956:Receptors, Cell Surface
keywords: CD10; CD177; HLA-DR; Neutrophil; Sepsis; mRNA