Genetic variation in IL18R1 and IL18 genes and Inteferon γ ELISPOT response to smallpox vaccination: an unexpected
Inna G Ovsyannikova1, Iana H Haralambieva, Richard B Kennedy
1Mayo Clinic Vaccine Research Group.
Background:
Genetic association studies demonstrated a role for cytokine proteins and cytokine or cytokine receptor gene polymorphisms in smallpox vaccine-induced adaptive immunity.
Methods:
We examined the association of genetic polymorphisms with cellular (interferon [IFN] γ enzyme-linked immunospot assay [ELISPOT]) immune response to smallpox vaccine in 1076 immunized individuals.
Results:
The majority of significant associations were discovered between single-nucleotide polymorphisms/haplotypes in IL18R1 and IL18 genes, in which we previously reported an association with vaccinia virus-induced neutralizing antibody titers in this study cohort. A functional coding IL18R1 polymorphism (rs1035130/Phe251Phe; P = .01) was significantly associated with an allele dose-related increase in IFN-γ production and was also associated with vaccinia-specific neutralizing antibody titers. Significant associations were also found between IL18R1 haplotypes and variations in IFN-γ ELISPOT responses (global P < .0001).
Conclusions:
Our data suggest the importance of variants in the IL18R1 and IL18 genetic loci for broad-based smallpox vaccine-induced adaptive immunity.
Related Concept Videos
02:32Exon Recombination
Exon shuffling follows “splice frame rules.” Each exon has three reading...
01:28Diversity of Antigen Receptors
Before encountering any antigen, lymphocytes express these receptors. On B cells, the antigen receptor is a membrane-bound antibody molecule called BCR; on T cells, it is a T cell receptor or TCR. B and T cell receptors are composed of two...