title: Autoantibodies to the A/B proteins of the heterogeneous nuclear ribonucleoprotein complex: novel tools for the diagnosis of rheumatic diseases.
abstract: Heterogeneous nuclear ribonucleoprotein (hnRNP) complexes are major constituents of the spliceosome. They are composed of approximately 30 different proteins which can bind to nascent pre-mRNA. Among these, the hnRNP-A/B proteins form a subgroup of highly related proteins: their N-terminal halves consist of two adjacent RNA-binding domains, whereas the C-terminal halves contain almost 50% glycine residues. These proteins represent a group of novel autoantigens which are targeted by autoantibodies from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD): thus, anti-A2/RA33 autoantibodies target the hnRNP proteins A2, B1, B2 (the 'RA33 complex'), and anti-A1 autoantibodies are directed to the hnRNP proteins A1 and A1b. In SLE, anti-hnRNP-A/B antibodies frequently occur together with antibodies to two other spliceosome-associated antigens, U1 small nuclear RNP (U1-snRNP) and Sm. Epitope-mapping studies have revealed that the major antibody binding sites are located in the RNA-binding regions. Furthermore, there is some indication of disease-specific epitope recognition. Studies in animal models have demonstrated the presence of anti-hnRNP-A/B antibodies in several lupus-prone mouse strains. Thus, autoantibodies to the spliceosomal hnRNP-A/B proteins are a common feature of RA, SLE, and MCTD. However, these diseases differ in their reactivities to other spliceosomal components, such as U1-snRNP and Sm antigens. Therefore, anti-hnRNP-A/B autoantibodies are not only valuable diagnostic markers but may also allow additional insights into the pathogenetic mechanisms of rheumatic autoimmune diseases.
authors.affiliation: Department of Rheumatology, University of Vienna, Austria.
authors.forename: G
authors.initials: G
authors.lastname: Steiner
authors.forename: K
authors.initials: K
authors.lastname: Skriner
authors.forename: J S
authors.initials: JS
authors.lastname: Smolen
mesh_terms: D000818:Animals; D001323:Autoantibodies; D001324:Autoantigens / Q000276:immunology; D015415:Biomarkers; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D006801:Humans; D051379:Mice; D012332:RNA, Heterogeneous Nuclear / Q000276:immunology*; D016601:RNA-Binding Proteins / Q000276:immunology*; D012216:Rheumatic Diseases / Q000175:diagnosis* / Q000209:etiology; D012261:Ribonucleoproteins / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B; D034441:Heterogeneous-Nuclear Ribonucleoproteins; D012332:RNA, Heterogeneous Nuclear; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; C439768:hnRNP A2