title: Increased IgA glycoprotein-2 specific antibody titres in refractory celiac disease.
abstract: OBJECTIVE
  In most cases celiac disease (CD) is successfully treated with a gluten-free diet (GFD). However, some patients become refractory to the GFD. Refractory CD (RCD) patients have an increased risk for developing enteropathy associated T-cell lymphoma and early diagnosis is therefore of importance. Currently, RCD diagnosis relies on endoscopy and adequate serological markers are lacking. Antibodies against glycoprotein-2 (GP2A) were described in Crohn's disease (CrD) and active CD but not in ulcerative colitis (UC), suggesting this is a specific marker for small intestinal lesions.
  
  
  METHODS
  Sera obtained from patients visiting our outpatient clinic for routine serological tests for diagnosis and/or follow-up of inflammatory bowel disease (n=78), active CD (n=45), GFD (n=34) and RCD (n=15) were analysed for GP2A titres.
  
  
  RESULTS
  Increased GP2A-IgA levels in CrD and active CD as compared to controls (p<0.001) and lack thereof in UC was confirmed. However, we could not confirm the association with small bowel localization within the CrD patient group. Within CD patients, we demonstrated a significant decrease of GP2A-IgA titres upon a GFD and increased levels in RCD patients as compared to patients on a GFD. Although GP2A-IgA was not associated with the degree of villous atrophy, GP2A-IgA levels were able to distinguish RCD patients from GFD patients (ROC AUC=0.79, p=0.002).
  
  
  CONCLUSIONS
  Follow-up of GP2A-IgA titres in CD patients on a GFD may help to identify patients at risk for developing RCD.
authors.affiliation: Department of Pathology,VU University Medical Center,Amsterdam The Netherlands. hj.bontkes@vumc.nl.
authors.forename: Sascha
authors.initials: S
authors.lastname: Gross
authors.affiliation: Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam The Netherlands.
authors.forename: Sjoerd F
authors.initials: SF
authors.lastname: Bakker
authors.affiliation: Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam The Netherlands.
authors.forename: Adriaan A
authors.initials: AA
authors.lastname: van Bodegraven
authors.affiliation: Department of Pathology,VU University Medical Center,Amsterdam The Netherlands.
authors.forename: Ingrid M W
authors.initials: IM
authors.lastname: van Hoogstraten
authors.affiliation: Department of Pathology,VU University Medical Center,Amsterdam The Netherlands.
authors.forename: Kyra A
authors.initials: KA
authors.lastname: Gelderman
authors.affiliation: Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam The Netherlands.
authors.forename: Gerd
authors.initials: G
authors.lastname: Bouma
authors.affiliation: Department of Gastroenterology and Hepatology VU University Medical Center Amsterdam The Netherlands.
authors.forename: Chris J
authors.initials: CJ
authors.lastname: Mulder
authors.affiliation: Department of Pathology,VU University Medical Center,Amsterdam The Netherlands.
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.affiliation: Department of Pathology,VU University Medical Center,Amsterdam The Netherlands.
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
mesh_terms: D000328:Adult; D000368:Aged; D000908:Antibodies, Fungal / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002446:Celiac Disease / Q000175:diagnosis* / Q000178:diet therapy / Q000276:immunology / Q000473:pathology; D003093:Colitis, Ulcerative / Q000276:immunology; D003424:Crohn Disease / Q000276:immunology / Q000473:pathology; D055050:Diet, Gluten-Free; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D011379:Prognosis; D012441:Saccharomyces cerevisiae / Q000276:immunology; D012710:Serum Albumin, Bovine / Q000276:immunology; D017211:Treatment Failure
chemical_list: D000908:Antibodies, Fungal; D001323:Autoantibodies; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; C072961:glycoprotein-2, pancreas; D012710:Serum Albumin, Bovine