The Function of PTPN22 and the Autoimmune Risk Variant LypW in Immune Responses to 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 disease, 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-specific CD4 T cells expressing effector cytokines, and failed to increase antibody affinity following TIV. No differences between LypW carriers and non-carriers were observed in virus-specific CD8 T cell responses, early interferon transcriptional responses, or myeloid APC costimulatory molecule upregulation. LypW association with defects in TIV-induced CD4 T cell expansion and antibody affinity maturation suggests that LypW may predispose to diminished capacity to generate protective immunity against influenza.