title: Autoimmune responses to proliferating cell nuclear antigen multiprotein complexes involved in cell proliferation are strongly associated with their structure and biologic function in patients with systemic lupus erythematosus.
abstract: OBJECTIVE
  To analyze the reaction of lupus sera with proliferating cell nuclear antigen (PCNA) multiprotein complexes (PCNA complexes), which are part of the protein machinery involved in cell proliferation.
  
  
  METHODS
  PCNA complexes were purified from rabbit thymus extract by affinity chromatography using anti-PCNA monoclonal antibodies (TOB7, TO17, and TO30); monomeric and trimeric PCNA forms (AK-PCNA) were purified using anti-PCNA serum AK. The reactions to these antigens of 10 anti-PCNA-positive and 40 anti-PCNA-negative sera selected from 560 lupus patients were tested by immunoblotting, immunoprecipitation, and enzyme-linked immunosorbent assays (ELISAs).
  
  
  RESULTS
  With one exception (serum OK), anti-PCNA-positive sera reacted exclusively with only the 34-kd polypeptide. In contrast, 14 of 40 anti-PCNA-negative sera reacted with multiple proteins within PCNA complexes. Most anti-PCNA-positive sera probably recognize as epitopes the binding sites for other proteins on PCNA, which are likely hidden when PCNA is complexed with other proteins. As a consequence, only serum OK reacted with the PCNA complex in a series of ELISAs. Using AK-PCNA as a competitive inhibitor, it was determined that serum OK reacts with both the 58-kd polypeptide and the 34-kd PCNA within complexes. Together with the results of a longitudinal analysis, these results suggest that the immune system of patient OK likely recognized the complexed PCNA protein, after which the autoimmune response spread to other elements of the complexes.
  
  
  CONCLUSIONS
  Intermolecular-intrastructural help, leading to the spread of autoimmune response from PCNA to other proteins associated with its biologic function, plays a crucial role in the induction of the autoimmune response seen in lupus patients.
authors.affiliation: Juntendo University School of Medicine, Tokyo, and Gunma University School of Medicine, Maebashi, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kogure
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Takasaki
authors.forename: Ken
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Yamada
authors.forename: Masuyuki
authors.initials: M
authors.lastname: Nawata
authors.forename: Keigo
authors.initials: K
authors.lastname: Ikeda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Matsushita
authors.forename: Ran
authors.initials: R
authors.lastname: Matsudaira
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kaneda
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Terasawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hashimoto
mesh_terms: D000911:Antibodies, Monoclonal; D015551:Autoimmunity / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D006801:Humans; D015151:Immunoblotting; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D011233:Precipitin Tests; D018809:Proliferating Cell Nuclear Antigen / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D018809:Proliferating Cell Nuclear Antigen