title: Complement activation in pediatric patients with recurrent acute otitis media.
abstract: OBJECTIVE
  Otitis media (OM) is one of the most common childhood diseases. The relative contribution of complement activation in protection and pathogenesis during OM remains largely unknown. The purpose of this study was to investigate the beneficial and pathogenic contributions of complement activation in the middle ear of pediatric patients with recurrent acute otitis media (rAOM), and therefore to provide a rational approach to prevent sequelae of OM such as hearing loss.
  
  
  METHODS
  Twenty children undergoing pressure equalization tube placement with or without adenoidectomy for rAOM were enrolled in the study. Bacterial cultures, enzyme-linked immunosorbent assay (ELISA) for complement components and cytokines and western blot for complement activation were performed on middle ear effusion (MEE) and serum samples. The levels of complement C3a, C5a and sC5-b9 in MEEs and serum samples were compared. The levels of these factors were also examined in regards to length of episode. Pearson's correlation coefficients were calculated on variables between C5a and IL-6 or IL-8. Complement gene expression in human middle ear epithelial (HMEE) cells induced by otopathogens was evaluated. Data were analyzed with Student's t test or the Mann-Whitney rank sum test. In all cases, a P value of <0.05 was set as the measure of significance.
  
  
  RESULTS
  Our data demonstrated that the complement classical/lectin, alternative and terminal pathways were activated in the middle ear of children with rAOM. Increased complement components of C3a, C5a and sC5-b9 in MEEs were detected in patients with the episode lasting more than six weeks. There was a strong correlation between C5a and IL-6 or IL-8 in the MEEs. Additionally, otopathogens induced enhanced gene expression of factor B and C3 in HMEE cells, which is beneficial for host defense against invading pathogens.
  
  
  CONCLUSIONS
  Our studies provided important new insights on how complement activation contributes to inflammatory process during rAOM. Knowledge of the activity of the complement pathway in patients with rAOM may stimulate the development of new strategies to prevent middle ear inflammatory tissue destruction by directing treatment to specific pathways within the complement cascade.
authors.affiliation: Department of Otolaryngology, College of Medicine and Public Health, The Ohio State University, Columbus, OH 43210, USA.
authors.forename: Yujuan
authors.initials: Y
authors.lastname: He
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Scholes
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Wiet
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.forename: Caitlin
authors.initials: C
authors.lastname: Clancy
authors.forename: Hua Hua
authors.initials: HH
authors.lastname: Tong
mesh_terms: D000208:Acute Disease; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D002675:Child, Preschool; D015331:Cohort Studies; D003167:Complement Activation; D003176:Complement C3 / Q000032:analysis; D003182:Complement C5 / Q000032:analysis; D003165:Complement System Proteins / Q000032:analysis*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D015850:Interleukin-6 / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D008876:Middle Ear Ventilation / Q000379:methods; D010034:Otitis Media with Effusion / Q000175:diagnosis* / Q000601:surgery; D016133:Polymerase Chain Reaction / Q000379:methods; D011446:Prospective Studies; D012008:Recurrence; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D003176:Complement C3; D003182:Complement C5; D015850:Interleukin-6; D016209:Interleukin-8; D003165:Complement System Proteins
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