title: Specific serum IgG at diagnosis of Staphylococcus aureus bloodstream invasion is correlated with disease progression.
abstract: Although Staphylococcus aureus is a prominent cause of infections, no vaccine is currently available. Active vaccination relies on immune memory, a core competence of the adaptive immune system. To elucidate whether adaptive immunity can provide protection from serious complications of S. aureus infection, a prospective observational study of 44 patients with S. aureus infection complicated by bacteremia was conducted. At diagnosis, serum IgG binding to S. aureus extracellular proteins was quantified on immunoblots and with Luminex-based FLEXMAP 3D™ assays comprising 64 recombinant S. aureus proteins. Results were correlated with the course of the infection with sepsis as the main outcome variable. S. aureus-specific serum IgG levels at diagnosis of S. aureus infection were lower in patients developing sepsis than in patients without sepsis (P<0.05). The pattern of IgG binding to eight selected S. aureus proteins correctly predicted the disease course in 75% of patients. Robust immune memory of S. aureus was associated with protection from serious complications of bacterial invasion. Serum IgG binding to eight conserved S. aureus proteins enabled stratification of patients with high and low risk of sepsis early in the course of S. aureus infections complicated by bacteremia.
  
  
  CONCLUSIONS
  S. aureus is a dangerous pathogen of ever increasing importance both in hospitals and in the community. Due to the crisis of antibiotic resistance, an urgent need exists for new strategies to combat S. aureus infections, such as vaccination. To date, however, all vaccine trials have failed in clinical studies. It is therefore unclear whether the adaptive immune system is at all able to control S. aureus in humans. The paper demonstrates the use of proteomics for providing an answer to this crucial question. It describes novel results of a prospective study in patients with S. aureus infection complicated by bloodstream invasion. Immune proteomic analysis shows that robust immune memory of S. aureus - reflected by strong serum IgG antibody binding to S. aureus antigens - is associated with clinical protection from sepsis. This lends support to the notion of a vaccine to protect against the most serious complications of S. aureus infection. Hence, the data encourage further efforts in vaccine development.
authors.affiliation: Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Stentzel
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; ZIK-FunGene Junior Research Group "Applied Proteomics", University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Nandakumar
authors.initials: N
authors.lastname: Sundaramoorthy
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; ZIK-FunGene Junior Research Group "Applied Proteomics", University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Michalik
authors.affiliation: Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Nordengrün
authors.affiliation: Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Kolata
authors.affiliation: Institute for Microbiology, University of Greifswald, 17489 Greifswald, Germany.
authors.forename: Peggy
authors.initials: P
authors.lastname: Kloppot
authors.affiliation: Institute for Microbiology, University of Greifswald, 17489 Greifswald, Germany; Microbial Proteomics Research Group, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Institute for Microbiology, Technical University of Braunschweig, 38106 Braunschweig, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Engelmann
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Leif
authors.initials: L
authors.lastname: Steil
authors.affiliation: Institute for Microbiology, University of Greifswald, 17489 Greifswald, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hecker
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany; ZIK-FunGene Junior Research Group "Applied Proteomics", University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Völker
authors.affiliation: Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Mary-Claire
authors.initials: MC
authors.lastname: Roghmann
authors.affiliation: Institute of Immunology and Transfusion Medicine, Department of Immunology, University Medicine Greifswald, 17475 Greifswald, Germany. Electronic address: broeker@uni-greifswald.de.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Bröker
mesh_terms: D016470:Bacteremia / Q000097:blood* / Q000453:epidemiology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013203:Staphylococcal Infections / Q000097:blood* / Q000453:epidemiology* / Q000382:microbiology; D013211:Staphylococcus aureus / Q000302:isolation & purification
chemical_list: D001426:Bacterial Proteins; D015415:Biomarkers; D007074:Immunoglobulin G
keywords: Bacteremia; Human; IgG; Protection; Serum antibodies; Staphylococcus aureus