Identification of CD4 T-Cell Epitopes in Soluble Liver Antigen/Liver Pancreas Autoantigen in Autoimmune Hepatitis
Background & Aims Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease associated with autoantibodies and liver-infiltrating lymphocytes. Although autoantibodies are tested routinely to diagnose and classify AIH, liver-infiltrating lymphocytes are regarded as the primary factor for disease pathogenesis. The purpose of this study was to identify and characterize autoantigenic peptides within human AIH-specific soluble liver antigen/liver pancreas antigen (SLA/LP) that are targeted by CD4 + T cells and restricted by the disease susceptibility gene HLA-DRB1*0301. Methods HLA-DRB1*0301 transgenic mice were immunized with SLA/LP. Antibody and T-cell responses were analyzed with SLA…
IFNL3/4 genotype is associated with altered immune cell populations in peripheral blood in chronic hepatitis C infection
Single-nucleotide polymorphisms near the interferon lambda 3 (IFNL3) gene predict outcomes to infection and anti-viral treatment in hepatitis C virus (HCV) infection. To identify IFNL3 genotype effects on peripheral blood, we collected phenotype data on 400 patients with genotype 1 chronic hepatitis C (CHC). The IFNL3 responder genotype predicted significantly lower white blood cells (WBCs), as well as lower absolute numbers of monocytes, neutrophils and lymphocytes for both rs8099917 and rs12979860. We sought to define the WBC subsets driving this association using flow cytometry of 67 untreated CHC individuals. Genotype-associated differences were seen in the ratio of CD4CD45RO+ to CD4CD4…