Antibody-based strategy might allow biopsy-free diagnosis of pediatric celiac disease

Last Updated: 2017-05-11

By Will Boggs MD

NEW YORK (Reuters Health) - A strategy based on antibodies might make it possible to diagnose pediatric celiac disease without the need for biopsy in some patients, researchers report.

Assays that measure immunoglobulin A against tissue transglutaminase (TTG) or endomysium (EMA) are currently used to select patients for subsequent diagnostic endoscopy and evaluation of intestinal histology or to rule out celiac disease. Another assay of IgG against deamidated gliadin peptides (DGL) is also under investigation. Whether these assays can be used to diagnose pediatric celiac disease remains controversial.

Dr. Thomas Mothes of University Hospital Leipzig, in Germany, and colleagues sought to validate two diagnostic procedures based on antibody assays for diagnosing pediatric celiac disease in their prospective trial of 898 children.

Using the TTG-only strategy, celiac disease would be diagnosed if antibody levels were 10 or more times the upper limit of normal and would be excluded if antibody levels were below the upper limit of normal. If neither criterion were met, biopsy would be necessary.

With the second strategy, combining TTG and DGL, celiac disease would be diagnosed when TTG or DGL antibody levels are at least 10 times the upper limit of normal and excluded when both antibody levels are below the upper limit of normal. Biopsy would be necessary otherwise.

Nearly 85% of children without celiac disease had levels of IgA-TTG and IgG-DGL below the upper limit of normal, whereas most celiac disease patients (76.4%) had IgA-TTG levels at least 10 times the upper limit of normal, the researchers report in Gastroenterology, online April 28.

The TTG-DGL procedure met the researchers' reliability criteria by having both positive and negative predictive value estimates about 95% and lower confidence bounds above 90%.

All patients whose IgA-TTG were at least 10 times the upper limit of normal also had positive IgA-EMA results and HLA status compatible with celiac disease (where measured).

Diagnostic performance did not differ meaningfully between symptomatic and asymptomatic patients.

Fewer than a quarter of patients showed intermediate antibody values that would indicate the need for biopsy.

“Our results have major personal and health care implications in clinical practice (avoiding many biopsies, reducing costs, endoscopy waiting times, patient risks, and delay of treatment),” the researchers conclude. “We have shown that HLA-typing as well as EMA tests are not required in unequivocal cases and that endoscopic procedures to assess duodenal biopsies are not required in a substantial proportion of pediatric patients with suspected celiac disease.”

Dr. Gabriel Samasca from Iuliu Hatieganu University of Medicine and Pharmacy, in Cluj-Napoca, Romania, who has published extensively on celiac disease and its diagnosis and treatment, told Reuters Health by email that the study brings nothing new to the table.

“The diagnosis of celiac disease remains the same,” Dr. Samasca said. “Celiac disease screening with TTG: if TTG is <100 - we will do duodenal biopsy; if TTG is >100 - we will do anti-EMA.”

“An immune-mediated disorder requires a close interaction of gastroenterologists and immunologists with a special interest in celiac disease,” he concluded. “The diagnosis of celiac disease remains a challenge for many gastroenterologists.”

EUROIMMUN Medizinische Labordiagnostika AG funded the study and provided a grant to Dr. Mothes, who is also a coinventor of a related patent. Dr. Mothes did not respond to a request for comments.

SOURCE: http://bit.ly/2q5mTGZ

Gastroenterology 2017.