title: Small ubiquitin-related modifiers: A novel and independent class of autoantigens in primary biliary cirrhosis.
abstract: Serum autoantibodies against components of nuclear dots (anti-NDs), namely PML and Sp100, are specifically detected in 20% to 30% of patients with primary biliary cirrhosis (PBC). Although anti-ND antibodies are nonpathogenic, the mechanisms that lead to this unique reactivity are critical to understanding the loss of immune tolerance in PBC. Importantly, Sp100 and PML are both covalently linked to small ubiquitin-related modifiers (SUMOs). Therefore, we investigated whether SUMO proteins are independent autoantigens in PBC and studied 99 PBC sera samples for reactivity against NDs, PML, and Sp100, as well as against SUMO-2 and SUMO-1 recombinant proteins. Autoantibodies against SUMO-2 and SUMO-1 were found in 42% and 15% of anti-ND-positive PBC sera, respectively. Anti-SUMO reactivity was not observed in anti-ND-negative sera. Anti-SUMO-2 autoantibodies were found in 58% of sera containing autoantibodies against both PML and Sp100 and were detected exclusively in sera containing anti-Sp100 autoantibodies. In conclusion, SUMO proteins constitute a novel and independent class of autoantigens in PBC. Furthermore, we believe our data emphasize the post-translational modification of lysine by either lipoylation in the case of AMA or SUMOylation in the case of specific anti-ND autoantibodies as the pivotal site for autoantibody generation in PBC.
authors.affiliation: Heinrich-Pette-Institut für experimentelle Virologie und Immunologie and the Universität Hamburg, Hamburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Janka
authors.forename: Carlo
authors.initials: C
authors.lastname: Selmi
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwin
authors.forename: Hans
authors.initials: H
authors.lastname: Will
authors.forename: Thomas
authors.initials: T
authors.lastname: Sternsdorf
mesh_terms: D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D034961:Antigens, Nuclear / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D001324:Autoantigens / Q000276:immunology*; D002645:Chickens; D005455:Fluorescent Antibody Technique; D006801:Humans; D015151:Immunoblotting; D008105:Liver Cirrhosis, Biliary / Q000276:immunology*; D008928:Mitochondria / Q000276:immunology; D009363:Neoplasm Proteins / Q000276:immunology; D009687:Nuclear Proteins / Q000276:immunology; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein / Q000737:chemistry / Q000276:immunology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000737:chemistry / Q000276:immunology*; D014157:Transcription Factors / Q000276:immunology; D025521:Tumor Suppressor Proteins
chemical_list: D000974:Antibodies, Antinuclear; D034961:Antigens, Nuclear; D001323:Autoantibodies; D001324:Autoantigens; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D025842:SUMO-1 Protein; C117909:SUMO2 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C066642:SP100 protein, human; C070576:PML protein, human