Immunologic response to vaccine challenge in pregnant PTPN22 R620W carriers and non-carriers

Shelly H. Tien, Juliet N. Crabtree, Heather L. Gray, Erik J. Peterson

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives Influenza infection is a significant cause of respiratory morbidity among pregnant women. Seasonal influenza vaccination engages innate immune receptors to promote protective immunity. A coding polymorphism (R620W) in PTPN22 imparts elevated risk for human infection and autoimmune disease, predisposes to diminished innate immune responses, and associates with reduced immunization responses. We sought to quantify the effects of PTPN22-R620W on humoral and cell-mediated immune responses to the inactivated influenza vaccine among healthy pregnant women. Study Design Immune responses were measured in healthy pregnant R620W carrier (n = 17) and non-carrier (n = 33) women receiving the 2013 quadrivalent inactivated influenza vaccine (Fluzone). Hemagglutination inhibition assays were performed to quantify neutralizing antibodies; functional influenza-reactive CD4 T cells were quantified by flow cytometry, and influenza-specific CD8 T cells were enumerated with MHC Class I tetramers. Antibody seroconversion data were evaluated by Chi-square analysis, and the Mann-Whitney or Wilcoxon signed-rank tests were applied to T cell response data. Results PTPN22 R620W carrier (n = 17) and non-carrier (n = 33) groups did not differ in age, parity, BMI, gestational age at time of vaccine, or history of prior influenza vaccination. After Fluzone exposure, 51.5% of non-carriers met criteria for antibody seroconversion to H1N1 influenza, compared with 23.5% of R620W carriers (p = 0.06). Influenza-reactive CD4 T cells showed modest increase at days 9–15 after vaccination in both R620W carriers and non-carriers (p = 0.02 and p = 0.04, respectively). However, there was no difference in overall response between the two groups (p = 0.6). The vaccine did not result in significant induction of influenza-specific CD8 T cells in either group. Conclusions There was no significant difference among healthy pregnant R620W carriers and non-carriers in H1N1 antibody seroconversion rates after influenza vaccination. Studies of larger cohorts will be needed to define the effect of PTPN22 risk allele carriage on antibody and T cell responses to influenza vaccination during pregnancy.

Original languageEnglish (US)
Article numbere0181338
JournalPloS one
Volume12
Issue number7
DOIs
StatePublished - Jul 2017

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health Award Number UL1TR000114. http://www. ctsi.umn.edu/about-ctsa-award. The University of Minnesota Center for Health Equity, 1P60MD003433 from the National Institute on Minority Health and Health Disparities. http://www. umnche.umn.edu/. The Department of Obstetrics, Gynecology, and Women?s Health, Division of Maternal-Fetal Medicine fellowship research stipend. http://www.obgyn.umn.edu/educationalopportunities/maternal-fetal-medicinefellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Publisher Copyright:
© 2017 Tien et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.

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