title: Clinical and serological features of patients with autoantibodies to GW/P bodies.
abstract: GW bodies (GWBs) are unique cytoplasmic structures involved in messenger RNA (mRNA) processing and RNA interference (RNAi). GWBs contain mRNA, components of the RNA-induced silencing complex (RISC), microRNA (miRNA), Argonaute proteins, the Ge-1/Hedls protein and other enzymes involving mRNA degradation. The objective of this study was to identify the target GWB autoantigens reactive with 55 sera from patients with anti-GWB autoantibodies and to identify clinical features associated with these antibodies. Analysis by addressable laser bead immunoassay (ALBIA) and immunoprecipitation of recombinant proteins indicated that autoantibodies in this cohort of anti-GWB sera were directed against Ge-1/Hedls (58%), GW182 (40%) and Ago2 (16%). GWB autoantibodies targeted epitopes that included the N-terminus of Ago2 and the nuclear localization signal (NLS) containing region of Ge-1/Hedls. Clinical data were available on 42 patients of which 39 were female and the mean age was 61 years. The most common clinical presentations were neurological symptoms (i.e. ataxia, motor and sensory neuropathy) (33%), Sjögren's syndrome (SjS) (31%) and the remainder had a variety of other diagnoses that included systemic lupus erythematosus (SLE), rheumatoid arthritis (RA) and primary biliary cirrhosis (PBC). Moreover, 44% of patients with anti-GWB antibodies had reactivity to Ro52. These studies indicate that Ge-1 is a common target of anti-GWB sera and the majority of patients in a GWB cohort had SjS and neurological disease.
authors.affiliation: Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Calgary, Canada.
authors.forename: Rahima A
authors.initials: RA
authors.lastname: Bhanji
authors.forename: Theophany
authors.initials: T
authors.lastname: Eystathioy
authors.forename: Edward K L
authors.initials: EK
authors.lastname: Chan
authors.forename: Donald B
authors.initials: DB
authors.lastname: Bloch
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
mesh_terms: D000328:Adult; D000368:Aged; D000918:Antibody Specificity; D060565:Argonaute Proteins; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000097:blood* / Q000276:immunology / Q000503:physiopathology*; D015852:Eukaryotic Initiation Factor-2 / Q000276:immunology; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007118:Immunoassay; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000276:immunology / Q000503:physiopathology; D009687:Nuclear Proteins / Q000276:immunology; D011506:Proteins; D016601:RNA-Binding Proteins; D012859:Sjogren's Syndrome / Q000276:immunology / Q000503:physiopathology
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D001323:Autoantibodies; D001324:Autoantigens; C507914:EDC4 protein, human; D015852:Eukaryotic Initiation Factor-2; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C465663:TNRC6A protein, human