title: Identification of immunodominant epitopes of alpha-crystallins recognized by antibodies in sera of patients with uveitis.
abstract: BACKGROUND
  A high incidence of autoantibodies to lens proteins has been found in sera of patients with uveitis. We showed previously that the anti-lens antibodies reacted predominantly with α-crystallins. The aim of the present study was to identify immunodominant epitopes within the protein chains of human αA- and αB-crystallin.
  
  
  METHODS
  Epitope specificities of antibodies to αA- and αB-crystallin were examined by ELISA using synthetic overlapping peptides, spanning the entire length of both α-crystallins. The peptides consisted of 25 amino acid residues, with an overlap of at least eight amino acids each. The synthetic peptides were tested against sera of 110 patients with different uveitis forms, classified according to anatomical location of intraocular inflammation.
  
  
  RESULTS
  Four immunodominant regions within the protein chains of αA- and αB-crystallin could be identified. These regions were recognized by antibodies in sera of 56% of uveitis patients. Anti-lens antibodies of IgG-type reacted preferentially with regions located at amino acid (aa) residues aa:69-93 and aa:137-161 of αA-crystallin as well as aa:69-110 and aa:137-161 of αB-crystallin. IgM antibodies recognized predominantly region aa:149-173 of αA-crystallin, and aa:69-110 and aa:151-175 of αB-crystallin. IgM antibodies directed to peptide aa:69-93 of αB-crystallin were found in sera of 30% of patients with intermediate uveitis.
  
  
  CONCLUSIONS
  Four immunodominant B-cell epitopes within the protein chains of αA- and αB-crystallin have been identified; however, no clear correlation with the anatomically defined uveitis subtypes has been found except for intermediate uveitis. Whether there may be a correlation with uveitis forms with similar etiopathogenesis has to be evaluated in further studies.
authors.affiliation: Centre for Ophthalmology, University of Tuebingen, Schleichstr. 12, 72076 Tuebingen, Germany. deshka.doycheva@med.uni-tuebingen.de
authors.forename: Deshka
authors.initials: D
authors.lastname: Doycheva
authors.forename: Beate
authors.initials: B
authors.lastname: Preuss
authors.forename: Christoph
authors.initials: C
authors.lastname: Deuter
authors.forename: Manfred
authors.initials: M
authors.lastname: Zierhut
authors.forename: Reinhild
authors.initials: R
authors.lastname: Klein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000595:Amino Acid Sequence; D001323:Autoantibodies / Q000097:blood*; D001324:Autoantigens / Q000276:immunology*; D002648:Child; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D018604:Epitope Mapping; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D014605:Uveitis / Q000276:immunology*; D038202:alpha-Crystallin A Chain / Q000276:immunology*; D038203:alpha-Crystallin B Chain / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D016056:Immunodominant Epitopes; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D010446:Peptide Fragments; D038202:alpha-Crystallin A Chain; D038203:alpha-Crystallin B Chain