title: Identification of three new autoantibodies associated with systemic lupus erythematosus using two proteomic approaches.
abstract: Our objective was to identify new serum autoantibodies associated with systemic lupus erythematosus (SLE), focusing on those found in patients with central nervous system (CNS) syndromes. Autoantigens in human brain proteins were screened by multiple proteomic analyses: two-dimensional polyacrylamide gel electrophoresis/Western blots followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis and immunoprecipitation followed by liquid chromatography-tandem mass spectrometry shotgun analysis. The presence of serum IgG autoantibodies against 11 selected recombinant antigens was assessed by Western blot and enzyme-linked immunosorbent assay (ELISA) in the sera of 106 SLE patients and 100 normal healthy controls. The O.D. values in sera from SLE patients were significantly higher than those of controls for the antigens crystallin αB (p = 0.0002), esterase D (p = 0.0002), APEX nuclease 1 (p < 0.0001), ribosomal protein P0 (p < 0.0001), and PA28γ (p = 0.0005); the first three are newly reported. The anti-esterase D antibody levels were significantly higher in the CNS group than in the non-CNS group (p = 0.016). Moreover, when the SLE patients were categorized using CNS manifestations indicating neurologic or psychiatric disorders, the anti-APEX nuclease 1 antibody levels were significantly elevated in SLE patients with psychiatric disorders (p = 0.037). In conclusion, the association of SLE with several new and previously reported autoantibodies has been demonstrated. Statistically significant associations between anti-esterase D antibodies and CNS syndromes as well as between anti-APEX nuclease 1 antibodies and psychiatric disorders in SLE were also demonstrated. The combined immunoproteomic approaches used in this study are reliable and effective methods for identifying SLE autoantigens.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical University, Tokyo, Japan. katsumata@ior.twmu.ac.jp
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Katsumata
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kawaguchi
authors.forename: Sayumi
authors.initials: S
authors.lastname: Baba
authors.forename: Seisuke
authors.initials: S
authors.lastname: Hattori
authors.forename: Koji
authors.initials: K
authors.lastname: Tahara
authors.forename: Kaori
authors.initials: K
authors.lastname: Ito
authors.forename: Tadao
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Nozomi
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oyama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kozuka-Hata
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hattori
authors.forename: Kinya
authors.initials: K
authors.lastname: Nagata
authors.forename: Hisashi
authors.initials: H
authors.lastname: Yamanaka
authors.forename: Masako
authors.initials: M
authors.lastname: Hara
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000097:blood*; D015153:Blotting, Western; D001923:Brain Chemistry; D043182:Carboxylesterase / Q000276:immunology; D002460:Cell Line; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000276:immunology; D015180:Electrophoresis, Gel, Two-Dimensional; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D047468:Immunoprecipitation; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D040901:Proteomics; D053719:Tandem Mass Spectrometry; D055815:Young Adult; D038203:alpha-Crystallin B Chain / Q000276:immunology
chemical_list: D001323:Autoantibodies; C059215:CRYAB protein, human; D038203:alpha-Crystallin B Chain; D043182:Carboxylesterase; C020118:ESD protein, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase