Autoimmune Variant PTPN22 C1858T Is Associated with Impaired Responses to Influenza Vaccination

Juliet N. Crabtree, Wenqian He, Weihua Guan, Mark Flage, Matthew S. Miller, Erik J Peterson

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

High-affinity-antibody production, T-cell activation, and interferon upregulation all contribute to protective immunity that occurs in humans following influenza immunization. Hematopoietic cell-specific PTPN22 encodes lymphoid phosphatase (Lyp), which regulates lymphocyte antigen receptor and pattern recognition receptor (PRR) signaling. A PTPN22 variant, R620W (LypW), predisposes to autoimmune and infectious diseases and confers altered signaling through antigen receptors and PRRs. We tested the hypothesis that LypW-bearing humans would have diminished immune response to trivalent influenza vaccine (TIV). LypW carriers exhibited decreased induction of influenza virus-specific CD4+ T cells expressing effector cytokines and failed to increase antibody affinity following TIV receipt. No differences between LypW carriers and noncarriers were observed in virus-specific CD8+ T-cell responses, early interferon transcriptional responses, or myeloid antigen-presenting cell costimulatory molecule upregulation. The association of LypW with defects in TIV-induced CD4+ T-cell expansion and antibody affinity maturation suggests that LypW may predispose individuals to have a diminished capacity to generate protective immunity against influenza virus.

Original languageEnglish (US)
Pages (from-to)248-257
Number of pages10
JournalJournal of Infectious Diseases
Volume214
Issue number2
DOIs
StatePublished - Jul 15 2016

Bibliographical note

Funding Information:
Financial support. This work was supported by the National Center for Advancing Translational Sciences, National Institutes of Health (NIH; award UL1TR000114) to E. J. P.; the University of Minnesota Immunology Training Grant, via the NIH (T32AI007313) to J. N. C.; and the Canadian Institutes of Health Research (operating grant to M. S. M.).

Publisher Copyright:
© 2016 The Author 2016.

Keywords

  • Affinity
  • CD4 T cells
  • Influenza
  • PTPN22
  • Vaccine

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