title: Otitis-prone Children Have Immunologic Deficiencies in Naturally Acquired Nasopharyngeal Mucosal Antibody Response after Streptococcus pneumoniae Colonization.
abstract: OBJECTIVE
  Acute otitis media (AOM) is the most common pediatric bacterial infection, and stringently defined otitis-prone (sOP) children have immunologic deficiencies. We recently found that nasopharyngeal (NP) colonization by Streptococcus pneumoniae (Spn) elicits a NP mucosal antibody response to vaccine candidate pneumococcal proteins that correlate with protection from AOM in non-sOP (NOP) children. Here, we sought to determine if sOP children experience significantly higher colonization rates with Spn than NOP children, develop lower naturally acquired NP mucosal antibody responses to those same pneumococcal proteins after colonization by Spn, and suffer greater frequency of AOM as a consequence.
  
  
  METHODS
  NP samples were collected from 130 NOP and 45 sOP children during 270 healthy visits and 201 AOM visits between 6 and 24 months of age. Spn were identified by standard culture. NP mucosal IgG and IgA levels to vaccine candidate proteins pneumococcal histidine triad protein D, pneumococcal choline binding protein A (PcpA) and pneumolysin D1 were measured by quantitative enzyme-linked immunosorbent assay.
  
  
  RESULTS
  sOP children had significantly higher colonization frequency by Spn (P < 0.0001) and significantly lower IgG and IgA levels to all 3 vaccine candidate proteins studied compared with NOP children (all P values <0.05) except IgG to Ply D1 (P = 0.31). Spn colonization in NOP children led to 2-fold to 5-fold increase in mucosal IgG and IgA levels to all 3 proteins (all P values <0.01), whereas Spn colonization in sOP children generally failed to elicit antibody responses (all P values >0.05). PcpA was unique in inducing significant increases in mucosal IgA (P = 0.02). When high mucosal IgG levels to all 3 proteins and IgA to PcpA were measured, they correlated with reduced AOM in sOP children.
  
  
  CONCLUSIONS
  sOP children experience significantly higher colonization rates with Spn, develop lower naturally acquired NP mucosal antibody responses to pneumococcal vaccine candidate proteins pneumococcal histidine triad protein D, PcpA and pneumolysin D1 after colonization by Spn, and suffer greater frequency of AOM if they do not generate high mucosal antibody to the studied proteins.
authors.affiliation: From the *Center for Infectious Diseases and Immunology, Rochester General Hospital Research Institute; †Legacy Pediatrics; and ‡College of Science, Rochester Institute of Technology, Rochester, New York.
authors.forename: Qingfu
authors.initials: Q
authors.lastname: Xu
authors.forename: Janet R
authors.initials: JR
authors.lastname: Casey
authors.forename: Emily
authors.initials: E
authors.lastname: Newman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Pichichero
mesh_terms: D056704:Adaptive Immunity; D000907:Antibodies, Bacterial / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology; D016022:Case-Control Studies; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007114:Immunization; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007223:Infant; D008297:Male; D009305:Nasopharynx / Q000276:immunology* / Q000382:microbiology*; D010033:Otitis Media / Q000276:immunology* / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000276:immunology* / Q000382:microbiology*; D020545:Respiratory Mucosa / Q000276:immunology* / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D007070:Immunoglobulin A; D007074:Immunoglobulin G