TY - JOUR
T1 - Impact of genetic variants in IL-4, IL-4 RA and IL-13 on the anti-pneumococcal antibody response
AU - Wiertsema, Selma P.
AU - Baynam, Gareth
AU - Khoo, Siew Kim
AU - Veenhoven, Reinier H.
AU - van Heerbeek, Niels
AU - Zhang, Guicheng
AU - Laing, Ingrid A.
AU - Rijkers, Ger T.
AU - Goldblatt, Jack
AU - Sanders, Elisabeth A.M.
AU - Le Souëf, Peter N.
PY - 2007/1/4
Y1 - 2007/1/4
N2 - 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 α chain (IL-4 Rα), 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 Rα 551Gln. Effects were stronger in gene haplotype combinations or in multiple haplotype combination analyses. Conclusion: 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.
AB - 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 α chain (IL-4 Rα), 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 Rα 551Gln. Effects were stronger in gene haplotype combinations or in multiple haplotype combination analyses. Conclusion: 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.
KW - Haplotypes
KW - Pneumococcal vaccine responsiveness
KW - Single nucleotide polymorphisms
UR - http://www.scopus.com/inward/record.url?scp=33845222648&partnerID=8YFLogxK
U2 - 10.1016/j.vaccine.2006.07.024
DO - 10.1016/j.vaccine.2006.07.024
M3 - Article
C2 - 16914241
AN - SCOPUS:33845222648
SN - 0264-410X
VL - 25
SP - 306
EP - 313
JO - Vaccine
JF - Vaccine
IS - 2
ER -