Persistently High Antibodies Reveal Non-responsive Celiac Disease

Celiac.com 04/07/2014 - Histologically non-responsive celiac disease (NRCD) is a potentially serious condition found in celiac disease patients who suffer persistent villous atrophy despite following a gluten-free diet (GFD).

Currently, the only way to monitor patient progress rely on invasive and costly serial duodenal biopsies. Looking for better options, a team of researchers recently set out to identify antibody biomarkers for celiac disease patients that do not respond to traditional therapy.

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The research team included B. N. Spatola, K. Kaukinen, P. Collin, M. Mäki, M. F. Kagnoff, and P. S. Daugherty. They are affiliated with the Department of Chemical Engineering, University of California, Santa Barbara in California, the Department of Gastroenterology and Alimentary Tract Surgery and the Center for Child Health Research at the University of Tampere and Tampere University Hospital in Tampere, Finland, with the Department of Medicine at Seinäjoki Central Hospital in Seinäjoki, Finland, and with the Laboratory of Mucosal Immunology in the Departments of Medicine and Pediatrics at the University of California San Diego in La Jolla, California.

Using flow cytometry to screen bacterial display peptide libraries, the team was able to identify the epitopes specifically recognized by antibodies from patients with NRCD, but not by antibodies from responsive celiac disease patients.

By comparing ELISA results for sera from 15 NRCD patients and 45 patients with responsive celiac disease, all on a strict GFD for at least 1 year, the team confirmed that deamidated gliadin was the antigen mimicked by library peptides.

They identified the dominant consensus epitope sequence by unbiased library screening QPxx(A/P)FP(E/D). The epitope sequence was highly similar to reported deamidated gliadin peptide (dGP) B-cell epitopes.

They also found that anti-dGP IgG measurement by ELISA discriminated between NRCD and responsive celiac disease patients with 87% sensitivity and 89% specificity.

Most importantly, they found that dGP antibody levels correlated with the severity of mucosal damage, meaning that IgG dGP levels may be useful in monitoring small intestinal mucosal recovery on a GFD in NCRD patients.

The team found that celiac patients with NRCD can be spotted by their increased levels of anti-dGP IgG antibodies even when the patients are following strict gluten-free diets

Lastly, they feel that anti-dGP IgG assays may be useful for monitoring mucosal damage and histological improvement in celiac disease patients on a strict GFD.

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