title: Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets.
abstract: BACKGROUND
  Meningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis.
  
  
  METHODS
  We used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis.
  
  
  RESULTS
  Unique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies.
  
  
  CONCLUSIONS
  Comparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Cordeiro
authors.forename: Rosiane Aparecida
authors.initials: RA
authors.lastname: Silva Pereira
authors.forename: Alex
authors.initials: A
authors.lastname: Chapeaurouge
authors.forename: Clarice Semião
authors.initials: CS
authors.lastname: Coimbra
authors.forename: Jonas
authors.initials: J
authors.lastname: Perales
authors.forename: Guilherme
authors.initials: G
authors.lastname: Oliveira
authors.forename: Talitah Michel
authors.initials: TM
authors.lastname: Sanchez Candiani
authors.forename: Roney Santos
authors.initials: RS
authors.lastname: Coimbra
mesh_terms: D000293:Adolescent; D000328:Adult; D002556:Cerebrospinal Fluid Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016234:Kallikrein-Kinin System / Q000502:physiology; D008297:Male; D013058:Mass Spectrometry; D008578:Meninges / Q000382:microbiology / Q000473:pathology / Q000821:virology; D008585:Meningitis, Meningococcal / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D008586:Meningitis, Pneumococcal / Q000175:diagnosis* / Q000188:drug therapy / Q000382:microbiology; D008587:Meningitis, Viral / Q000175:diagnosis* / Q000188:drug therapy / Q000821:virology; D020543:Proteome / Q000032:analysis; D040901:Proteomics / Q000379:methods*; D055815:Young Adult
chemical_list: D002556:Cerebrospinal Fluid Proteins; D020543:Proteome