title: Serologic Anti-GP2 Antibodies Are Associated with Genetic Polymorphisms, Fibrostenosis, and Need for Surgical Resection in Crohn's Disease.
abstract: The presentation of Crohn's disease (CD) is heterogeneous and often leads to serious complications and need for surgery. We tested serum anti-zymogen granule glycoprotein 2 (GP2) antibodies, including its novel isoform alpha, for association with genetic variants, diagnosis, disease stratification, and prediction of CD courses in a combined cross-sectional and cohort study.
  
  
  
  Serum samples of 303 CD, 108 ulcerative colitis, 72 other inflammatory gastrointestinal diseases, and 206 controls without predominant gastrointestinal diseases controls (HC) were tested for the presence of Anti-GP2 and Anti-Saccharomyces cervisiae (ASCA) by enzyme-linked immunosorbent assay. Genetic analysis was performed using the Illumina Immunochip.
  
  
  
  GP2 IgA and IgG had the highest discriminatory capability for CD versus ulcerative colitis and CD versus inflammatory gastrointestinal diseases. We identified an association of GP2 IgA and IgG each with 5 distinct single-nucleotide polymorphisms. Levels of anti-GP2 IgG were moderately associated with ileal disease location. Interestingly, both, anti-GP2 IgA and IgG were exclusively associated with the occurrence of stenosis and need for surgery, independently of disease location, but not with fistulizing CD, early disease onset or disease activity. ASCA IgG and IgA were qualitatively and quantitatively linked to CD, CD complications, and need for surgery. Increased levels of ASCA IgG and IgA and positivity for ASCA IgG, but neither levels nor positivity for GP2 IgG or IgA were predictive of the earlier occurrence of complications or surgery.
  
  
  
  Anti-GP2 antibodies may aid as a tool for diagnosis and differentiation of CD and could indicate a more complicated CD course.
authors.affiliation: *Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; †Department of Internal Medicine I, University Medical Center Regensburg, Regensburg, Germany; ‡Department of Quantitative Health Sciences, Cleveland Clinic Foundation, Cleveland, Ohio; §Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland; ‖Faculty of Science, Brandenburg University of Technology Cottbus-Senftenberg, Senftenberg, Germany; ¶Institute of Molecular and Clinical Immunology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany; **Institute of Medical Informatics and Statistics, Christian-Albrechts-University of Kiel, Kiel, Germany; ††Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; and ‡‡Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio.
authors.forename: Frauke
authors.initials: F
authors.lastname: Degenhardt
authors.forename: Andrea
authors.initials: A
authors.lastname: Dirmeier
authors.forename: Rocio
authors.initials: R
authors.lastname: Lopez
authors.forename: Sylvia
authors.initials: S
authors.lastname: Lang
authors.forename: Claudia
authors.initials: C
authors.lastname: Kunst
authors.forename: Dirk
authors.initials: D
authors.lastname: Roggenbuck
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Silke
authors.initials: S
authors.lastname: Szymczak
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.forename: Frank
authors.initials: F
authors.lastname: Klebl
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Florian
authors.initials: F
authors.lastname: Rieder
mesh_terms: D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000235:genetics; D000908:Antibodies, Fungal / Q000097:blood / Q000235:genetics; D001323:Autoantibodies / Q000097:blood / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000097:blood / Q000276:immunology / Q000601:surgery; D003251:Constriction, Pathologic / Q000276:immunology; D003424:Crohn Disease / Q000097:blood* / Q000276:immunology / Q000601:surgery; D003430:Cross-Sectional Studies; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000276:immunology*; D012441:Saccharomyces cerevisiae / Q000276:immunology*
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000908:Antibodies, Fungal; D001323:Autoantibodies; D015415:Biomarkers; C489339:GP2 protein, human; D058851:GPI-Linked Proteins; C049937:anti-IgA; C048844:anti-IgG