title: Modeling of celiac disease immune response and the therapeutic effect of potential drugs.
abstract: BACKGROUND
  Celiac disease (CD) is an autoimmune disorder that occurs in genetically predisposed people and is caused by a reaction to the gluten protein found in wheat, which leads to intestinal villous atrophy. Currently there is no drug for treatment of CD. The only known treatment is lifelong gluten-free diet. The main aim of this work is to develop a mathematical model of the immune response in CD patients and to predict the efficacy of a transglutaminase-2 (TG-2) inhibitor as a potential drug for treatment of CD.
  
  
  RESULTS
  A thorough analysis of the developed model provided the following results:1. TG-2 inhibitor treatment leads to insignificant decrease in antibody levels, and hence remains higher than in healthy individuals.2. TG-2 inhibitor treatment does not lead to any significant increase in villous area.3. The model predicts that the most effective treatment of CD would be the use of gluten peptide analogs that antagonize the binding of immunogenic gluten peptides to APC. The model predicts that the treatment of CD by such gluten peptide analogs can lead to a decrease in antibody levels to those of normal healthy people, and to a significant increase in villous area.
  
  
  CONCLUSIONS
  The developed mathematical model of immune response in CD allows prediction of the efficacy of TG-2 inhibitors and other possible drugs for the treatment of CD: their influence on the intestinal villous area and on the antibody levels. The model also allows to understand what processes in the immune response have the strongest influence on the efficacy of different drugs. This model could be applied in the pharmaceutical R&D arena for the design of drugs against autoimmune small intestine disorders and on the design of their corresponding clinical trials.
authors.affiliation: Institute for System Biology SPb, Moscow, Russia. demin_jr@insysbio.ru
authors.forename: Oleg O
authors.initials: OO
authors.lastname: Demin
authors.forename: Sergey V
authors.initials: SV
authors.lastname: Smirnov
authors.forename: Victor V
authors.initials: VV
authors.lastname: Sokolov
authors.forename: Lourdes
authors.initials: L
authors.lastname: Cucurull-Sanchez
authors.forename: Cesar
authors.initials: C
authors.lastname: Pichardo-Almarza
authors.forename: M Victoria
authors.initials: MV
authors.lastname: Flores
authors.forename: Neil
authors.initials: N
authors.lastname: Benson
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Demin
mesh_terms: D056704:Adaptive Immunity / Q000187:drug effects*; D000906:Antibodies / Q000097:blood / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology; D002446:Celiac Disease / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology*; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D005983:Glutens / Q000737:chemistry; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D019409:Interleukin-15 / Q000276:immunology; D007421:Intestine, Small / Q000276:immunology; D018448:Models, Immunological; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D015203:Reproducibility of Results; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000906:Antibodies; D004791:Enzyme Inhibitors; D019409:Interleukin-15; D010446:Peptide Fragments; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins