title: Autoimmune Variant PTPN22 C1858T Is Associated With Impaired Responses to Influenza Vaccination.
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.
authors.affiliation: Center for Immunology Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School.
authors.forename: Juliet N
authors.initials: JN
authors.lastname: Crabtree
authors.affiliation: Department of Microbiology, School of Graduate Studies, Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Wenqian
authors.initials: W
authors.lastname: He
authors.affiliation: Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis.
authors.forename: Weihua
authors.initials: W
authors.lastname: Guan
authors.affiliation: Center for Immunology.
authors.forename: Mark
authors.initials: M
authors.lastname: Flage
authors.affiliation: Department of Biochemistry and Biomedical Sciences, Institute for Infectious Diseases Research, McMaster Immunology Research Center, McMaster University, Hamilton, Canada.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Miller
authors.affiliation: Center for Immunology Division of Rheumatic and Autoimmune Diseases, Department of Medicine, University of Minnesota Medical School.
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Peterson
mesh_terms: D056704:Adaptive Immunity; D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007252:Influenza Vaccines / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D050505:Mutant Proteins / Q000235:genetics; D009975:Orthomyxoviridae / Q000276:immunology*; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; D007252:Influenza Vaccines; D050505:Mutant Proteins; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22
keywords: CD4 T cells; PTPN22; affinity; influenza; vaccine