A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.

Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to...

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Main Authors: Inna G Ovsyannikova, Daniel J Schaid, Beth R Larrabee, Iana H Haralambieva, Richard B Kennedy, Gregory A Poland
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2017-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5291460?pdf=render
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spelling doaj-e5f86f21d0e3416d9c5d1aef4b3781372020-11-25T02:13:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01122e017126110.1371/journal.pone.0171261A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.Inna G OvsyannikovaDaniel J SchaidBeth R LarrabeeIana H HaralambievaRichard B KennedyGregory A PolandHuman antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.http://europepmc.org/articles/PMC5291460?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Inna G Ovsyannikova
Daniel J Schaid
Beth R Larrabee
Iana H Haralambieva
Richard B Kennedy
Gregory A Poland
spellingShingle Inna G Ovsyannikova
Daniel J Schaid
Beth R Larrabee
Iana H Haralambieva
Richard B Kennedy
Gregory A Poland
A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
PLoS ONE
author_facet Inna G Ovsyannikova
Daniel J Schaid
Beth R Larrabee
Iana H Haralambieva
Richard B Kennedy
Gregory A Poland
author_sort Inna G Ovsyannikova
title A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
title_short A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
title_full A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
title_fullStr A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
title_full_unstemmed A large population-based association study between HLA and KIR genotypes and measles vaccine antibody responses.
title_sort large population-based association study between hla and kir genotypes and measles vaccine antibody responses.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2017-01-01
description Human antibody response to measles vaccine is highly variable in the population. Host genes contribute to inter-individual antibody response variation. The killer cell immunoglobulin-like receptors (KIR) are recognized to interact with HLA molecules and possibly influence humoral immune response to viral antigens. To expand on and improve our previous work with HLA genes, and to explore the genetic contribution of KIR genes to the inter-individual variability in measles vaccine-induced antibody responses, we performed a large population-based study in 2,506 healthy immunized subjects (ages 11 to 41 years) to identify HLA and KIR associations with measles vaccine-induced neutralizing antibodies. After correcting for the large number of statistical tests of allele effects on measles-specific neutralizing antibody titers, no statistically significant associations were found for either HLA or KIR loci. However, suggestive associations worthy of follow-up in other cohorts include B*57:01, DQB1*06:02, and DRB1*15:05 alleles. Specifically, the B*57:01 allele (1,040 mIU/mL; p = 0.0002) was suggestive of an association with lower measles antibody titer. In contrast, the DQB1*06:02 (1,349 mIU/mL; p = 0.0004) and DRB1*15:05 (2,547 mIU/mL; p = 0.0004) alleles were suggestive of an association with higher measles antibodies. Notably, the associations with KIR genotypes were strongly nonsignificant, suggesting that KIR loci in terms of copy number and haplotypes are not likely to play a major role in antibody response to measles vaccination. These findings refine our knowledge of the role of HLA and KIR alleles in measles vaccine-induced immunity.
url http://europepmc.org/articles/PMC5291460?pdf=render
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