title: Concordance in Anti-OmpC and Anti-I2 Indicate the Influence of Genetic Predisposition: Results of a European Study of Twins with Crohn's Disease.
abstract: OBJECTIVE
  An adaptive immunological response to microbial antigens has been observed in Crohn's disease (CD). Intriguingly, this serological response precedes the diagnosis in some patients and has also been observed in healthy relatives. We aimed to determine whether genetic factors are implicated in this response in a CD twin cohort.
  
  
  METHODS
  In total, 82 twin pairs (Leuven n = 13, Maastricht n = 8, Örebro n = 61) took part: 81 pairs with CD (concordant monozygotic n = 16, discordant monozygotic n = 22, concordant dizygotic n = 3, discordant dizygotic n = 40) and 1 monozygotic pair with both CD and ulcerative colitis. Serology for Pseudomonas fluorescens-related protein (anti-I2), Escherichia coli outer membrane porin C (anti-OmpC), CBir1flagellin (anti-CBir1) and antibodies to oligomannan (anti-Saccharomyces cerevisiae antibody [ASCA]) was determined by standardized enzyme-linked immunoassay.
  
  
  RESULTS
  All markers were more often present in CD twins than in their healthy twin siblings. Using the intraclass correlation coefficient (ICC), agreements in concentrations of anti-OmpC and anti-I2 were observed in discordant monozygotic but not in discordant dizygotic twin pairs with CD (anti-OmpC, ICC 0.80 and -0.02, respectively) and (anti-I2, ICC 0.56 and 0.05, respectively). In contrast, no agreements were found in anti-CBir, immunoglobulin (Ig) G ASCA and ASCA IgA.
  
  
  CONCLUSIONS
  We show that anti-I2 and anti-CBir1 statuses have specificity for CD and confirm previous reported specificities for anti-OmpC and ASCA. Based on quantitative analyses and observed ICCs, genetics seems to predispose to the anti-OmpC and anti-I2 response but less to ASCA and anti-CBir1 responses.
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Amcoff
authors.affiliation: KU Leuven, Department of Microbiology and Immunology, Rega Institute, Herestraat 49, B-3000 Leuven, Belgium VIB, Center for the Biology of Disease, Herestraat 49, B-3000 Leuven, Belgium Microbiology Unit, Faculty of Sciences and Bioengineering Sciences, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Joossens
authors.affiliation: Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Pierik
authors.affiliation: Gastroenterology, University Hospital Maastricht, Maastricht, The Netherlands.
authors.forename: Daisy
authors.initials: D
authors.lastname: Jonkers
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Bohr
authors.affiliation: Gastroenterology, Catholic University of Leuven (KUL), Leuven, Belgium.
authors.forename: Sofie
authors.initials: S
authors.lastname: Joossens
authors.affiliation: Department of Gastroenterology-Hepatology, Zuyderland Medical Center, Sittard, Netherlands.
authors.forename: Mariëlle
authors.initials: M
authors.lastname: Romberg-Camps
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Nils
authors.initials: N
authors.lastname: Nyhlin
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Wickbom
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Rutgeerts
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
authors.forename: Curt
authors.initials: C
authors.lastname: Tysk
authors.affiliation: Institute of Environmental Medicine, Unit of Intervention and Implementation Research, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Bodin
authors.affiliation: Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jean-Frederic
authors.initials: JF
authors.lastname: Colombel
authors.affiliation: Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden jonas.halfvarson@regionorebrolan.se.
authors.forename: Jonas
authors.initials: J
authors.lastname: Halfvarson
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D000908:Antibodies, Fungal / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D003093:Colitis, Ulcerative / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000382:microbiology; D003424:Crohn Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000382:microbiology; D004797:Enzyme-Linked Immunosorbent Assay; D029968:Escherichia coli Proteins / Q000276:immunology; D005060:Europe; D005260:Female; D005408:Flagellin / Q000097:blood; D020022:Genetic Predisposition to Disease; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D008297:Male; D008875:Middle Aged; D018272:Porins / Q000276:immunology*; D011551:Pseudomonas fluorescens / Q000276:immunology; D012189:Retrospective Studies; D029701:Saccharomyces cerevisiae Proteins / Q000276:immunology; D018089:Superantigens / Q000276:immunology*; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D000908:Antibodies, Fungal; D015415:Biomarkers; C502160:CBir1 flagellin; D029968:Escherichia coli Proteins; D007070:Immunoglobulin A; D007074:Immunoglobulin G; C113724:OmpC protein; C469916:PfiT protein, Pseudomonas fluorescens; D018272:Porins; D029701:Saccharomyces cerevisiae Proteins; D018089:Superantigens; D005408:Flagellin
keywords: Crohn’s disease; genetics; serology