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

J Infect Dis. 2016 Jul 15;214(2):248-57. doi: 10.1093/infdis/jiw126. Epub 2016 Mar 30.


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.

Keywords: CD4 T cells; PTPN22; affinity; influenza; vaccine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptive Immunity*
  • Adolescent
  • Adult
  • Antibodies, Viral / blood*
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Immunity, Innate*
  • Influenza Vaccines / immunology*
  • Male
  • Middle Aged
  • Mutant Proteins / genetics
  • Orthomyxoviridae / immunology*
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22 / genetics*
  • Young Adult


  • Antibodies, Viral
  • Influenza Vaccines
  • Mutant Proteins
  • PTPN22 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 22