title: Impact of genetic variants in IL-4, IL-4 RA and IL-13 on the anti-pneumococcal antibody response.
abstract: BACKGROUND
  Significant differences in immune responses upon vaccination have been described, suggesting genetics are important in determining the magnitude of vaccine responses. The interleukin (IL)-4 pathway, including IL-4, IL-13 and the IL-4 receptor alpha chain (IL-4 Ralpha), is central to humoral responses and therefore could have an impact on vaccine responsiveness.
  
  
  OBJECTIVE
  To investigate whether single nucleotide polymorphisms (SNPs) in the IL-4, IL-13 and IL-4 RA genes influence pneumococcal serotype-specific IgG antibody responses.
  
  
  METHODS
  SNPs in the IL-4 gene (C -589T, G2979T), the IL-13 gene (G -1112A, Arg130Gln) and in the IL-4 RA gene (Ile50Val, Gln551Arg) were investigated in isolation and in combination, for their influence on serotype-specific IgG antibody responses upon combined pneumococcal conjugate and polysaccharide vaccinations in children with a history of recurrent otitis media.
  
  
  RESULTS
  Lower antibody responses were observed for alleles previously associated with atopy, IL-4 -589T, IL-4 2979T and IL-4 Ralpha 551Gln. Effects were stronger in gene haplotype combinations or in multiple haplotype combination analyses.
  
  
  CONCLUSIONS
  This study highlights the importance of host genetic factors in vaccine responses. Furthermore, it supports the approach of studying the effect of combinations of multiple alleles, in haplotypes or in combinations of haplotypes, on complex phenotypes within a biological pathway.
authors.affiliation: Department of Paediatric Immunology, Wilhelmina Children's Hospital, University Medical Center Utrecht, 3584 EA Utrecht, The Netherlands.
authors.forename: Selma P
authors.initials: SP
authors.lastname: Wiertsema
authors.forename: Gareth
authors.initials: G
authors.lastname: Baynam
authors.forename: Siew-Kim
authors.initials: SK
authors.lastname: Khoo
authors.forename: Reinier H
authors.initials: RH
authors.lastname: Veenhoven
authors.forename: Niels
authors.initials: N
authors.lastname: van Heerbeek
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.forename: Ingrid A
authors.initials: IA
authors.lastname: Laing
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.forename: Elisabeth A M
authors.initials: EA
authors.lastname: Sanders
authors.forename: Peter N
authors.initials: PN
authors.lastname: Le Souëf
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D018793:Interleukin-13 / Q000235:genetics*; D015847:Interleukin-4 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D018793:Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4