Immune Response Distinguishes Celiac Disease From Gluten Sensitivity

By Will Boggs MD

August 31, 2020

NEW YORK (Reuters Health) - The IgG antibody response to gluten is different in people with celiac disease and non-celiac gluten sensitivity, respectively, researchers report.

"What's exciting about these results is that for the first time they demonstrate a clear difference in the immune response to gluten between patients with celiac disease and patients with wheat sensitivity in the absence of celiac disease, which is commonly referred to as non-celiac gluten or wheat sensitivity (NCGS)," Dr. Armin Alaedini of Columbia University Medical Center, in New York City, told Reuters Health by email.

IgG antibody to gluten increases to similar levels in patients with celiac disease and NCGS, but whether B cells react differently to gluten in these conditions has been unclear.

Dr. Alaedini and colleagues evaluated the IgG subclass distribution in celiac disease and NCGS and its relationship to intestinal cell damage in their study of 40 patients with biopsy-proven celiac disease, 80 individuals with NCGS, 40 healthy volunteers, 49 patients with irritable-bowel syndrome, and 63 patients with functional dyspepsia.

Among patients with celiac disease, the anti-gliadin IgG response was comprised mainly of IgG1 and IgG3, whose levels were significantly increased in comparison with the NCGS group and healthy controls. IgG2 was also increased compared with the healthy group.

In contrast, the NCGS group had significantly elevated IgG4 (compared with the celiac disease and healthy groups) and IgG2 (compared with the healthy group), the researchers report in Gastroenterology.

There was no significant association between any anti-gliadin IgG subclass and the Marsh type, HLA-DQ2/DQ8 status, or fulfillment of diagnostic criteria for irritable-bowel syndrome or functional dyspepsia.

Serum concentrations of intestinal fatty acid-binding protein (FABP2), a specific marker of intestinal epithelial-cell damage, were elevated to a similar extent in the celiac disease and NCGS groups, compared with the healthy group.

Within the celiac disease group, anti-gliadin IgG3 correlated with FABP2, whereas FABP2 levels in the NCGS group correlated with anti-gliadin IgG4 and weakly with IgG1.

"As a disease progresses (such as in an infection or an allergy), the IgG antibody subclass distribution may evolve to take on a more or less inflammatory character." Dr. Alaedini explained. "The data in our study show that celiac disease and NCGS are quite different in the subclass distribution of IgG response to gluten, as well as in the relationship between these subclasses and the presumed intestinal pathology. This contrast is likely reflective of differences in the progression and disease relevance of B-cell immune responses in celiac disease versus NCGS."

"The prominence of the IgG3 subclass and its close relationship with the autoimmune response and intestinal cell turnover in celiac disease is suggestive of repeated activation of gluten-specific naive B cells," he said. "This is in spite of the chronic nature of celiac disease, which one might expect to lead to activation of memory cells in response to gluten exposure and an eventual subclass switch to the less inflammatory IgG2 and IgG4. If immune cells (including T cells and B cells) can be driven towards more tolerogenic and less inflammatory phenotypes, we may be able to prevent or reduce the severity of the adverse immune reaction to gluten in patients."

"I hope these data help in increasing awareness among physicians that sensitivity to wheat in the absence of celiac disease is a distinct condition with a biological basis," Dr. Alaedini said. "While a complex clinical work up is currently needed to evaluate patients, we will likely have established biomarkers in the future to help physicians in diagnosing patients more easily and accurately."

"The information we are learning about NCGS and celiac disease through studying these conditions together can also provide important insights for developing effective treatments beyond dietary restriction," he said.

SOURCE: https://bit.ly/3giCs5g Gastroenterology, online July 20, 2020.

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