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

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

Author information

1
Center for Immunology Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School.
2
Department of Microbiology, School of Graduate Studies, Icahn School of Medicine at Mount Sinai, New York, New York.
3
Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
4
Center for Immunology.
5
Department of Biochemistry and Biomedical Sciences, Institute for Infectious Diseases Research, McMaster Immunology Research Center, McMaster University, Hamilton, Canada.

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.

KEYWORDS:

CD4 T cells; PTPN22; affinity; influenza; vaccine

PMID:
27034343
PMCID:
PMC4918823
DOI:
10.1093/infdis/jiw126
[Indexed for MEDLINE]
Free PMC Article

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