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Published on: January 17, 2014
Association of CD14 promoter polymorphism with otitis media and pneumococcal vaccine responses
S P Wiertsema1, S-K Khoo, G Baynam
1Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, The Netherlands.
Insights
The CD14 C-159T gene variant may protect young children from recurrent ear infections. This genetic factor also enhances immune responses to pneumococcal vaccines in early childhood.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Innate immunity is crucial for infant protection against infections due to immature adaptive immunity.
- CD14 is vital for innate immunity and defense against otitis media pathogens.
- The CD14 C-159T polymorphism (T allele) correlates with higher CD14 levels.
Purpose of the Study:
- To determine if the CD14 C-159T allele protects children against recurrent acute otitis media.
- To investigate the association between CD14 genotype and acute otitis media episodes.
- To compare immune responsiveness, specifically pneumococcal antibody levels, across CD14 genotypes.
Main Methods:
- Retrospective and prospective evaluation of CD14 promoter genotype and acute otitis media episodes in 300 children.
- Analysis of serotype-specific immunoglobulin G (IgG) antibody responses post-pneumococcal vaccination based on CD14 genotype.
Main Results:
- An age-dependent protective effect of the TT genotype against acute otitis media was observed in children aged 12-24 months (41% vs. 79% for CC homozygotes, P=0.004).
- This association was not significant in older children.
- TT homozygotes exhibited elevated serotype-specific anti-pneumococcal IgG antibody levels.
Conclusions:
- Genetic variation in CD14 influences protection against middle ear infections in childhood.
- CD14 genotype impacts pneumococcal vaccine responsiveness.
- These findings highlight CD14's role in immune-mediated outcomes during early life.
Abstract:
Innate immunity is of particular importance for protection against infection during early life, when adaptive immune responses are immature. CD14 plays key roles in innate immunity, including in defense against pathogens associated with otitis media, a major pediatric health care issue. The T allele of the CD14 C-159T polymorphism has been associated with increased serum CD14 levels. Our objective was to investigate the hypothesis that the CD14 C-159T allele is protective against recurrent acute otitis media in children. The association between the CD14 promoter genotype and the number of acute otitis media episodes was evaluated both retrospectively and prospectively in a cohort of 300 children. Serotype-specific immunoglobulin G (IgG) antibody responses after pneumococcal vaccinations were examined according to CD14 genotype to compare immune responsiveness across genotypes. An age-dependent association was found: compared with that for CC homozygotes aged between 12 to 24 months, TT homozygotes had fewer episodes of acute otitis media (79 versus 41%, respectively; P = 0.004); this relationship was absent in older children. Additionally, TT homozygotes showed higher serotype-specific anti-pneumococcal IgG antibody levels. Our data suggest that genetic variation in CD14, a molecule at the interface of innate and adaptive immune responses, plays a key role in the defense against middle ear disease in childhood and in pneumococcal vaccine responsiveness. These findings are likely to be important to these and other immune-mediated outcomes in early life.
