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Published on: January 17, 2014
Otitis-prone Children Have Immunologic Deficiencies in Naturally Acquired Nasopharyngeal Mucosal Antibody Response
Qingfu Xu1, Janet R Casey, Emily Newman
1From 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.
Insights
Stringently otitis-prone children have higher Streptococcus pneumoniae colonization and lower antibody responses, leading to more frequent acute otitis media. Developing mucosal immunity to pneumococcal proteins is crucial for preventing AOM in these vulnerable children.
Area of Science:
- Pediatric infectious diseases
- Immunology
- Microbiology
Background:
- Acute otitis media (AOM) is a common pediatric bacterial infection.
- Stringently otitis-prone (sOP) children exhibit immunologic deficiencies.
- Nasopharyngeal (NP) colonization by Streptococcus pneumoniae (Spn) can elicit protective antibody responses in non-sOP (NOP) children.
Purpose of the Study:
- To determine if sOP children have higher Spn colonization rates than NOP children.
- To investigate if sOP children develop lower NP mucosal antibody responses to pneumococcal proteins after Spn colonization.
- To assess if sOP children suffer a greater frequency of AOM due to these factors.
Main Methods:
- NP samples collected from 130 NOP and 45 sOP children aged 6-24 months.
- Spn identified by standard culture.
- NP mucosal IgG and IgA levels to pneumococcal histidine triad protein D, PcpA, and Ply D1 measured by ELISA.
Main Results:
- sOP children showed significantly higher Spn colonization frequency (P < 0.0001).
- sOP children had significantly lower IgG and IgA levels to most pneumococcal proteins compared to NOP children (P < 0.05).
- Spn colonization increased antibody levels in NOP children but generally failed to elicit responses in sOP children, except for IgA to PcpA.
Conclusions:
- sOP children experience higher Spn colonization and reduced mucosal antibody responses.
- These factors contribute to a greater frequency of AOM in sOP children lacking robust antibody immunity.
- Developing high mucosal antibody levels to pneumococcal proteins is associated with reduced AOM in sOP children.
Objectives:
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.
Conclusion:
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.
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