title: Persistence of elevated deamidated gliadin peptide antibodies on a gluten-free diet indicates nonresponsive coeliac disease.
abstract: BACKGROUND
  Histologically nonresponsive coeliac disease (NRCD) is a potentially serious condition diagnosed during the follow-up of coeliac disease (CD) when patients have persistent villous atrophy despite following a gluten-free diet (GFD).
  
  
  OBJECTIVE
  As current assessments of recovery are limited to invasive and costly serial duodenal biopsies, we sought to identify antibody biomarkers for CD patients that do not respond to traditional therapy.
  
  
  METHODS
  Bacterial display peptide libraries were screened by flow cytometry to identify epitopes specifically recognised by antibodies from patients with NRCD, but not by antibodies from responsive CD patients. Deamidated gliadin was confirmed to be the antigen mimicked by library peptides using ELISA with sera from NRCD (n = 15) and responsive CD (n = 45) patients on a strict GFD for at least 1 year.
  
  
  RESULTS
  The dominant consensus epitope sequence identified by unbiased library screening QPxx(A/P)FP(E/D) was highly similar to reported deamidated gliadin peptide (dGP) B-cell epitopes. Measurement of anti-dGP IgG titre by ELISA discriminated between NRCD and responsive CD patients with 87% sensitivity and 89% specificity. Importantly, dGP antibody titre correlated with the severity of mucosal damage indicating that IgG dGP titres may be useful to monitor small intestinal mucosal recovery on a GFD.
  
  
  CONCLUSIONS
  The finding of increased levels of anti-dGP IgG antibodies in CD patients on strict GFDs effectively identifies patients with NRCD. Finally, anti-dGP IgG assays may be useful to monitor mucosal damage and histological improvement in CD patients on a strict GFD.
authors.affiliation: Department of Chemical Engineering, University of California, Santa Barbara, CA, USA.
authors.forename: B N
authors.initials: BN
authors.lastname: Spatola
authors.forename: K
authors.initials: K
authors.lastname: Kaukinen
authors.forename: P
authors.initials: P
authors.lastname: Collin
authors.forename: M
authors.initials: M
authors.lastname: Mäki
authors.forename: M F
authors.initials: MF
authors.lastname: Kagnoff
authors.forename: P S
authors.initials: PS
authors.lastname: Daugherty
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D002446:Celiac Disease / Q000178:diet therapy* / Q000276:immunology; D055050:Diet, Gluten-Free; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005903:Gliadin / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007413:Intestinal Mucosa / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000276:immunology; D012680:Sensitivity and Specificity
chemical_list: D000906:Antibodies; D015415:Biomarkers; D007074:Immunoglobulin G; D010455:Peptides; D005903:Gliadin