Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines.
Details
Serval ID
serval:BIB_44965C59FD25
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines.
Journal
Genome medicine
Working group(s)
Milieu Intérieur Consortium
Contributor(s)
Abel L., Alcover A., Aschard H., Astrom K., Bousso P., Bruhns P., Cumano A., Demangel C., Deriano L., Di Santo J., Dromer F., Duffy D., Eberl G., Enninga J., Fellay J., Gelpi O., Gomperts-Boneca I., Hasan M., Hercberg S., Lantz O., Leclerc C., Mouquet H., Pellegrini S., Pol S., Rausell A., Rogge L., Sakuntabhai A., Schwartz O., Schwikowski B., Shorte S., Soumelis V., Tangy F., Tartour E., Toubert A., Touvier M., Ungeheuer M.N., Albert M.L., Quintana-Murci L.
ISSN
1756-994X (Electronic)
ISSN-L
1756-994X
Publication state
Published
Issued date
27/07/2018
Peer-reviewed
Oui
Volume
10
Number
1
Pages
59
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: epublish
Publication Status: epublish
Abstract
Humoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that human genetic variation influences (i) serum immunoglobulin levels, (ii) seroconversion rates, and (iii) intensity of antigen-specific immune responses. Here, we evaluated the impact of intrinsic (age and sex), environmental, and genetic factors on the variability of humoral response to common pathogens and vaccines.
We characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age- and sex-stratified cohort of 1000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG, and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~ 5 million genetic variants and antibody responses using single marker and gene burden tests.
We identified age and sex as important determinants of humoral immunity, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leukocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations.
Using extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrated that age, sex, and specific human genetic variants contribute to inter-individual variability in humoral immunity. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis.
ClinicalTrials.gov , NCT01699893.
We characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age- and sex-stratified cohort of 1000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG, and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~ 5 million genetic variants and antibody responses using single marker and gene burden tests.
We identified age and sex as important determinants of humoral immunity, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leukocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations.
Using extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrated that age, sex, and specific human genetic variants contribute to inter-individual variability in humoral immunity. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis.
ClinicalTrials.gov , NCT01699893.
Keywords
Age, GWAS, HLA, Human genomics, Humoral immunity, Immunoglobulins, Infection, Serology, Sex, Vaccination
Pubmed
Web of science
Open Access
Yes
Create date
22/08/2018 8:52
Last modification date
20/08/2019 13:49
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