title: Autoantibodies that stabilize U1snRNP are a significant component of human autoantibodies to snRNP and delay proteolysis of sm antigens in vitro.
abstract: OBJECTIVE
  Autoantibodies to U1-C have been considered a minor component of anti-snRNP (nRNP, Sm) response based on Western blotting. However, we have previously shown that virtually all human anti-nRNP sera contain antibodies to native U1-C, as well as novel autoantibodies that stabilize the molecular interaction of the U1-C-Sm core particle. The biological significance of stabilizing antibodies was investigated by titering anti-U1-C/U1-A compared to stabilizing antibodies, and by examining the effects of stabilizing antibodies on antigen processing.
  
  
  METHODS
  Autoantibodies to individual native components of U1snRNP (immunoprecipitation of RNase-treated cell extract) and stabilizing antibodies (dissociation of snRNP on anti-Sm monoclonal antibodies by 1 M MgCl2) in human autoimmune sera were titered. Effects of stabilizing antibodies on proteolysis were assessed by incubating UsnRNP with anti-snRNP/Sm autoimmune sera prior to protease digestion.
  
  
  RESULTS
  Autoantibodies to native U1-C and U1-C-Sm core particle stabilizing antibodies were universally present in human anti-nRNP or anti-nRNP + anti-Sm sera, but not in anti-Sm sera. Antibodies to U1-A were less common. The titers of stabilizing antibodies were higher than those of antibodies to U1-C (p < 0.01), indicating that the stabilizing antibodies were a significant component of the anti-snRNP response. The stabilizing anti-nRNP, but not anti-Sm antibodies, protects the Sm core particle from dissociation and proteolysis.
  
  
  CONCLUSIONS
  Autoantibodies stabilizing the U1-C-Sm core particle were universally present in anti-nRNP sera and delay proteolysis of the Sm core particle. They may suppress spreading of the autoimmune response to Sm by delaying or altering processing of the Sm core proteins by antigen-presenting cells.
authors.affiliation: Division of Rheumatology and Clinical Immunology, Department of Medicine, University of Florida, Gainesville, FL 32610-0221, USA. satohm@medicine.ufl.edu
authors.forename: Minoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Jun
authors.initials: J
authors.lastname: Akaogi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Dina C
authors.initials: DC
authors.lastname: Nacionales
authors.forename: Hideo
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yoshioki
authors.initials: Y
authors.lastname: Yamasaki
authors.forename: Westley H
authors.initials: WH
authors.lastname: Reeves
mesh_terms: D000918:Antibody Specificity; D001323:Autoantibodies / Q000032:analysis / Q000276:immunology*; D001324:Autoantigens; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000032:analysis / Q000276:immunology*; D017411:Ribonucleoproteins, Small Nuclear / Q000032:analysis / Q000276:immunology*; D012494:Sampling Studies; D012680:Sensitivity and Specificity; D055517:snRNP Core Proteins
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D015415:Biomarkers; D017412:Ribonucleoprotein, U1 Small Nuclear; D017411:Ribonucleoproteins, Small Nuclear; D055517:snRNP Core Proteins; D010447:Peptide Hydrolases