title: Autoantibodies to GW bodies and other autoantigens in primary biliary cirrhosis.
abstract: Autoantibodies to intracellular targets in mitochondria and nuclei are serological hallmarks of primary biliary cirrhosis (PBC). One of the most recently identified cellular targets of PBC autoantibodies is a novel cytoplasmic structure referred to as GW bodies [GWB, G (glycine) W (tryptophan)-containing bodies (GWB)]. GWB are indentified as discrete cytoplasmic domains that are involved in mRNA processing via the RNA interference (RNAi) pathway. Key components of GWB include the proteins GW182, Ago2, RNA-associated protein 55 (RAP55) and Ge-1/Hedls. The primary objective was to study the frequency and clinical association of antibodies directed to GWB components, in 109 PBC patients. Autoantibodies to mitochondrial antigen-pyruvate dehydrogenase complex (M2), branched-chain 2-oxo-acid dehydrogenase complex and 2-oxo glutarate dehydrogenase complex (3E-BPO), gp210, sp100, promyelocytic leukaemia cell antigen (PML) and liver kidney microsomal-1 antigen (LKM-1) were detected by a line immunoassay and antibodies to GWB (GW182, RAP55, Ge-1, GW2, GW3) and glutamate receptor interacting protein (GRIP)-associated protein-1 (GRASP-1), by an addressable laser bead immunoassay (ALBIA). The most common GWB autoantigen targets were: RAP55-28%, GW182-12%, GW2-2% and antibodies to GRASP-1-17%. By comparison, the frequency of reactivity to established PBC autoantigens was: gp210, 27%; sp100, 27% and PML, 17%. None of the autoantibodies were associated with differences in Mayo risk score or liver decompensation. This study is the first study to show that antibodies to RAP55, GW182 and GRASP-1 are the most common GWB targets in PBC.
authors.affiliation: Department of Medicine, University of Calgary, AB, Canada.
authors.forename: L M
authors.initials: LM
authors.lastname: Stinton
authors.forename: M
authors.initials: M
authors.lastname: Swain
authors.forename: R P
authors.initials: RP
authors.lastname: Myers
authors.forename: A A
authors.initials: AA
authors.lastname: Shaheen
authors.forename: M J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D000328:Adult; D000368:Aged; D034961:Antigens, Nuclear / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D022083:Cytoplasmic Structures / Q000276:immunology*; D005260:Female; D006801:Humans; D007655:Ketoglutarate Dehydrogenase Complex / Q000276:immunology; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins / Q000276:immunology; D011768:Pyruvate Dehydrogenase Complex / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology; D012189:Retrospective Studies; D012261:Ribonucleoproteins / Q000276:immunology; D014157:Transcription Factors / Q000276:immunology; D025521:Tumor Suppressor Proteins / Q000276:immunology; D055815:Young Adult
chemical_list: D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; C507914:EDC4 protein, human; C063865:NUP210 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D011506:Proteins; D011768:Pyruvate Dehydrogenase Complex; D016601:RNA-Binding Proteins; C510649:RNA-associated protein 55, human; D012261:Ribonucleoproteins; C465663:TNRC6A protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C060729:anti-liver kidney microsome antibody; C066642:SP100 protein, human; C070576:PML protein, human; D007655:Ketoglutarate Dehydrogenase Complex