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Persistence of elevated deamidated gliadin peptide antibodies on a gluten‐free diet indicates nonresponsive coeliac disease
Author(s) -
Spatola B. N.,
Kaukinen K.,
Collin P.,
Mäki M.,
Kagnoff M. F.,
Daugherty P. S.
Publication year - 2014
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/apt.12603
Subject(s) - coeliac disease , gliadin , epitope , medicine , antibody , gluten free , immunology , titer , flow cytometry , antigen , disease , gluten , pathology
Summary 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 ). Aim 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.