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Clinical and Vaccine Immunology, August 2006, p. 892-897, Vol. 13, No. 8
1071-412X/06/$08.00+0     doi:10.1128/CVI.00100-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Association of CD14 Promoter Polymorphism with Otitis Media and Pneumococcal Vaccine Responses

S. P. Wiertsema,1,2 S.-K. Khoo,2 G. Baynam,2 R. H. Veenhoven,3 I. A. Laing,2 G. A. Zielhuis,4 G. T. Rijkers,1,5 J. Goldblatt,2,6 P. N. LeSouëf,2 and E. A. M. Sanders1*

Department of Pediatric Immunology, University Medical Center Utrecht, Utrecht, The Netherlands,1 School of Paediatrics and Child Health, University of Western Australia, Perth, Australia,2 Department of Pediatrics, Spaarne Hospital, Hoofddorp, The Netherlands,3 Department of Epidemiology and Biostatistics, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands,4 Department of Medical Microbiology and Immunology, St. Antonius Hospital, Nieuwegein, The Netherlands,5 Genetic Services of Western Australia, Perth, Australia6

Received 16 February 2006/ Returned for modification 17 May 2006/ Accepted 9 June 2006

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.

* Corresponding author. Mailing address: Department of Pediatric Immunology, UMCU, Lundlaan 6, KC03.063.0, 3584 EA, Utrecht, The Netherlands. Phone: 31 30 2504000. Fax: 31 30 2505350. E-mail: l.sanders{at}umcutrecht.nl.

Clinical and Vaccine Immunology, August 2006, p. 892-897, Vol. 13, No. 8
1071-412X/06/$08.00+0     doi:10.1128/CVI.00100-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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