title: Autoantibodies directed to novel components of the PM/Scl complex, the human exosome.
abstract: The autoantigenic polymyositis/scleroderma (PM/Scl) complex was recently shown to be the human homologue of the yeast exosome, which is an RNA-processing complex. Our aim was to assess whether, in addition to targeting the known autoantigens PM/Scl-100 and PM/Scl-75, autoantibodies also target recently identified components of the PM/Scl complex. The prevalence of autoantibodies directed to six novel human exosome components (hRrp4p, hRrp40p, hRrp41p, hRrp42p, hRrp46p, hCsl4p) was determined in sera from patients with idiopathic inflammatory myopathy (n = 48), scleroderma (n = 11), or the PM/Scl overlap syndrome (n = 10). The sera were analyzed by enzyme-linked immunosorbent assays and western blotting using the affinity-purified recombinant proteins. Our results show that each human exosome component is recognized by autoantibodies. The hRrp4p and hRrp42p components were most frequently targeted. The presence of autoantibodies directed to the novel components of the human exosome was correlated with the presence of the anti-PM/Scl-100 autoantibody in the sera of patients with idiopathic inflammatory myopathy (IIM), as was previously found for the anti-PM/Scl-75 autoantibody. Other clear associations between autoantibody activities were not found. These results further support the conception that the autoimmune response may initially be directed to PM/Scl-100, whereas intermolecular epitope spreading may have caused the autoantibody response directed to the associated components.
authors.affiliation: Department of Biochemistry, University of Nijmegen, NL-6500 HB Nijmegen, The Netherlands.
authors.forename: Rick
authors.initials: R
authors.lastname: Brouwer
authors.forename: Wilma T M
authors.initials: WT
authors.lastname: Vree Egberts
authors.forename: Gerald J D
authors.initials: GJ
authors.lastname: Hengstman
authors.forename: Reinout
authors.initials: R
authors.lastname: Raijmakers
authors.forename: Baziel G M
authors.initials: BG
authors.lastname: van Engelen
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Seelig
authors.forename: Manfred
authors.initials: M
authors.lastname: Renz
authors.forename: Rudolf
authors.initials: R
authors.lastname: Mierau
authors.forename: Ekkehard
authors.initials: E
authors.lastname: Genth
authors.forename: Ger J M
authors.initials: GJ
authors.lastname: Pruijn
authors.forename: Walther J
authors.initials: WJ
authors.lastname: van Venrooij
mesh_terms: D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005095:Exoribonucleases / Q000276:immunology; D063326:Exosome Multienzyme Ribonuclease Complex; D006801:Humans; D009687:Nuclear Proteins / Q000145:classification / Q000276:immunology*; D017285:Polymyositis / Q000276:immunology*; D011994:Recombinant Proteins; D012595:Scleroderma, Systemic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D009687:Nuclear Proteins; D011994:Recombinant Proteins; D005095:Exoribonucleases; D063326:Exosome Multienzyme Ribonuclease Complex; C077044:EXOSC10 protein, human