title: Bioinformatic and immunological analysis reveals lack of support for measles virus related mimicry in Crohn's disease.
abstract: BACKGROUND
  A link between measles virus and Crohn's disease (CD) has been postulated. We assessed through bioinformatic and immunological approaches whether measles is implicated in CD induction, through molecular mimicry.
  
  
  METHODS
  The BLAST2p program was used to identify amino acid sequence similarities between five measles virus and 56 intestinal proteins. Antibody responses to measles/human mimics were tested by an in-house ELISA using serum samples from 50 patients with CD, 50 with ulcerative colitis (UC), and 38 matched healthy controls (HCs).
  
  
  RESULTS
  We identified 15 sets of significant (>70%) local amino acid homologies from two measles antigens, hemagglutinin-neuraminidase and fusion-glycoprotein, and ten human intestinal proteins. Reactivity to at least one measles 15-meric mimicking peptide was present in 27 out of 50 (54%) of patients with CD, 24 out of 50 (48%) with UC (CD versus UC, p = 0.68), and 13 out of 38 (34.2%) HCs (CD versus HC, p = 0.08). Double reactivity to at least one measles/human pair was present in four out of 50 (8%) patients with CD, three out of 50 (6%) with UC (p = 0.99), and in three out of 38 (7.9%) HCs (p >0.05 for all). Titration experiments yielded different extinction curves for anti-measles and anti-human intestinal double-reactive antibodies. Epitope prediction algorithms and three-dimensional modeling provided bioinformatic confirmation for the observed antigenicity of the main measles virus epitopic regions.
  
  
  CONCLUSIONS
  Measles sequences mimicking intestinal proteins are frequent targets of antibody responses in patients with CD, but this reactivity lacks disease specificity and does not initiate cross-reactive responses to intestinal mimics. We conclude that there is no involvement of measles/human molecular mimicry in the etiopathogenesis of CD.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Polymeros
authors.affiliation: Hepatogastroenterology Unit, 2nd Department of Internal Medicine, National and Kapodistrian University of Athens, Attikon University General Hospital, Rimini 1, Haidari 12462, Athens, Greece. ztsiamoulos@nhs.net.
authors.forename: Zacharias P
authors.initials: ZP
authors.lastname: Tsiamoulos
authors.forename: Andreas L
authors.initials: AL
authors.lastname: Koutsoumpas
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Smyk
authors.forename: Maria G
authors.initials: MG
authors.lastname: Mytilinaiou
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Triantafyllou
authors.forename: Dimitrios P
authors.initials: DP
authors.lastname: Bogdanos
authors.forename: Spiros D
authors.initials: SD
authors.lastname: Ladas
mesh_terms: D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000032:analysis; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000276:immunology*; D019295:Computational Biology; D003424:Crohn Disease / Q000276:immunology*; D003937:Diagnosis, Differential; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008459:Measles virus / Q000276:immunology*; D008875:Middle Aged
chemical_list: D000956:Antigens, Viral