Authors:
Anderson D, Fakiola M, Hales BJ, Pennell CE, Thomas WR, Blackwell JM
Authors notes:
Genes and Immunity. 2015;16(5):289-96
Keywords:
Streptococcus pneumoniae, single-nucleotide polymorphisms, vaccine, vaccine design
Abstract:
Streptococcus pneumoniae causes invasive pneumococcal disease.
Delayed development of antibodies to S. pneumoniae in infancy is associated with the development of atopy and asthma.
Pneumococcal surface protein C (PspC) is a vaccine candidate and variation in its choline-binding region is associated with invasive disease.
This study examined 523 060 single-nucleotide polymorphisms in The Western Australian Pregnancy Cohort (Raine) Study to find loci influencing immunoglobulin G1 (IgG1) responses to PspC measured at age 14 years (n=1152).
Genome-wide significance (top SNP rs9275596; P=3.1 × 10-14) was only observed at human leucocyte antigen (HLA).
Imputed HLA amino-acid polymorphisms showed the strongest associations at positions DRB1 47, 13SRG and 11SP, and at DQA1 34, DQB1 167R and HLA-B 95 W (P=1.2 × 10-9).
Conditional analyses showed independent contributions from DRB1 47 and DQB1 167R to the signal at rs9275596, supported by an omnibus test showing a strong signal for the haplotype DRB1_47_DQB1_167 (P=9.02 × 10-15).
In silico analysis showed that DRB1 four-digit allele groups defined by DRB1 47F bind to a greater complexity of core 9-mer epitopes compared with DRB1 47Y, especially across repeats in the C-term choline-binding region.
Consequent differences in CD4 T-cell help for IgG1 to PspC could have implications for vaccine design.
Further analysis in other cohorts is merited.