New research has identified permanent “immune scarring” in celiac disease which persists despite recovery on a gluten-free diet. It helps explain why patients never recover tolerance for gluten. The evidence encourages early diagnosis of celiac and has implications in the search for a cure.
The study showed, “that subsets of long-lived immune cells that reside in tissues such as the intestine and function to protect us under normal conditions can be permanently lost as a consequence of chronic inflammation,” says Toufic Mayassi, graduate student in the committee on immunology at University of Chicago, who was the primary researcher and author.
In early inflammation the healthy immune arsenal continues to operate but eventually reaches a tipping point. Then pro-inflammatory cells overtake the niche previously occupied by the protective cells. In celiac these new cells are activated by gluten.
“We were able to identify a subset of pre-celiac patients where the immune compartment was not yet fully altered suggesting interventions in these individuals may allow for the preservation of their healthy immune makeup. With the current treatment strategies this would only be accomplished by placing these individuals on a gluten-free diet prior to the full development of the disease,” says Mayassi.
“In the same vein, we observe in a subset of young children where the diagnosis was made early that they preserve various features of the healthy immune compartment suggesting again if treated early the impact of disease manifestation may be blunted. We will be able to determine whether or not these children maintain the healthy subset as we study them over time,” he adds.
Once they are supplanted, the gut does not recover the population of cells normally involved in preventing infections and tumors.
“That celiac patients permanently lose these cells leaves a functional vacancy that may predispose these patients to future infections and development of intestinal tumors,” says Mayassi. “Work towards a cure for celiac disease will need to consider that complete effectiveness of a treatment may depend on fully restoring the immune composition found in the gut in a manner that fully recapitulates the healthy gut.”
Celiac provides a good model for inflammatory disease because it can be controlled by removing gluten. Mayassi says the findings may help understand other conditions where tissue-resident immunity is profoundly altered, such as inflammatory bowel disease.