title: Distinct Anti-IFI16 and Anti-GP2 Antibodies in Inflammatory Bowel Disease and Their Variation with Infliximab Therapy.
abstract: Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gut, partly driven by defects in the expression and function of pattern recognition receptors, including the IFI16 protein. Because this protein is a target for autoantibodies and its aberrant expression was reported in colonic mucosa from active patients with ulcerative colitis, we studied its expression and specific seroresponse in patients with IBD before and after infliximab (IFX) therapy.
  
  
  
  Anti-IFI16 antibodies (IgG and IgA subtypes) were measured in the sera of 74 patients with IBD: 48 patients with Crohn's disease (CD) and 26 patients with ulcerative colitis, prospectively harvested before and after IFX therapy. Anti-GP2 antibodies (both IgG and IgA subtypes) were also tested for comparison. The patient antibody statuses were qualitatively and quantitatively associated with disease phenotype and response to IFX therapy.
  
  
  
  Significantly higher titers of anti-IFI16 IgG were found in both CD and ulcerative colitis patients compared with healthy controls. Anti-IFI16 IgA titers were also present in patients with CD. Anti-GP2 IgG subtype titers were significantly increased in patients with CD, as were IgA subtype titers. Significant changes in anti-IFI16 IgG subtype titers were observed after IFX in patients with CD who correlated with clinical remission or response.
  
  
  
  Our results highlight the importance of IFI16 in IBD pathogenesis showing that its de novo overexpression in the gut epithelial cells leads to a breakdown in immune tolerance and the subsequent development of specific autoantibodies. Anti-IFI16 IgG antibodies hold the potential to serve as a biomarker of response to IFX therapy.
authors.affiliation: *Viral Pathogenesis Unit, Department of Public Health and Pediatric Sciences, Turin Medical School, Turin, Italy; †Virology Unit, Department of Translational Medicine, Novara Medical School, Novara, Italy; ‡Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; §Department of Biomedical Sciences for Health, University of Milan, Milan, Italy; ‖Pathology Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy; ¶Division of Pediatrics, Department of Health Sciences, Novara Medical School, Novara, Italy; **Pathology Unit, Department of Health Sciences, Novara Medical School, Novara, Italy; ††Institute of Biotechnology, Faculty of Environment and Natural Sciences, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; ‡‡GA Generic Assays GmbH, Dahlewitz, Germany; and §§Interdisciplinary Research Center of Autoimmune Diseases (IRCAD), Novara Medical School, Novara, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Caneparo
authors.forename: Luca
authors.initials: L
authors.lastname: Pastorelli
authors.forename: Laura Francesca
authors.initials: LF
authors.lastname: Pisani
authors.forename: Barbara
authors.initials: B
authors.lastname: Bruni
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.forename: Maurizio
authors.initials: M
authors.lastname: Vecchi
authors.forename: Santo
authors.initials: S
authors.lastname: Landolfo
authors.forename: Marisa
authors.initials: M
authors.lastname: Gariglio
authors.forename: Marco
authors.initials: M
authors.lastname: De Andrea
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000888:Antibodies, Anti-Idiotypic / Q000097:blood; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000188:drug therapy / Q000276:immunology; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D005765:Gastrointestinal Agents / Q000627:therapeutic use*; D006801:Humans; D000069285:Infliximab / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000276:immunology; D010750:Phosphoproteins / Q000276:immunology; D011446:Prospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D015415:Biomarkers; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; D005765:Gastrointestinal Agents; D009687:Nuclear Proteins; D010750:Phosphoproteins; C049937:anti-IgA; C048844:anti-IgG; C076700:IFI16 protein, human; D000069285:Infliximab