New research may lead to a test for gluten sensitivity

September 16, 2020

Gluten sensitive patients produce unique antibodies to gluten that might be used for diagnosis

By Amy Ratner, Medical and Science News Analyst

When someone has symptoms of celiac disease but tests negative for the condition, they are often put on a gluten-free diet and lumped into the category of non-celiac gluten sensitivity without a definitive diagnosis.

But that could change based on research from Columbia University that has found people with gluten sensitivity produce high levels of antibodies to gluten different from those measured to diagnose celiac disease. Although they have symptoms, those with gluten sensitivity do not have the blood markers or intestinal damage of celiac disease.

Implications for celiac disease

The antibodies identified by researchers could be used in the future to help doctors more easily detect who has gluten sensitivity. And findings of the study, published online in the journal Gastroenterology, could also have implications for those with celiac disease.

The inflammatory response caused by antibodies produced by people with gluten sensitivity is also different from the response triggered in celiac disease, according to the study by Armin Alaedini, PhD, scientific director at the Celiac Disease Center, Columbia University Medical Center, and colleagues.

Related: Get a complete guide to gluten sensitivity

Celiac disease patients produce Immunoglobulin G (IgG) antibodies with the potential for a strong inflammatory response linked to autoimmune activity and damage to cells in the intestine, while gluten sensitive patients produce IgG antibodies with a more restrained inflammatory reaction, he said.

Immune reaction

Study results suggest that celiac disease patients generate a strong inflammatory response each time they eat gluten, while the immune system in people with gluten sensitivity learns from its earlier encounters with gluten and generates less-inflammatory responses subsequently, said Alaedini.

B-cells: immune cells that produce antibodies after being activated by T-cells

In celiac disease, B-cells never get accustomed to encountering gluten and respond each time as though it’s the first time, causing the strong inflammatory reaction. Meanwhile in gluten sensitivity the immune system gets more used to encountering gluten and becomes more tolerant of it over time.

“If we can drive the immune cells of celiac [disease] patients toward their less inflammatory states, we may be able to prevent or reduce the severity of the immunologic reaction to gluten,” said Alaedini, who  has done previous studies searching for the biological basis of gluten sensitivity.

Salvo Alesci, MD, Beyond Celiac chief scientist and strategy officer, said findings of the research, particularly if confirmed larger studies in the future, can help scientists better understand differences in the immune response underlying the celiac disease versus non-celiac gluten sensitivity. “Perhaps most importantly, from a practical perspective, the results can provide a non-invasive tool in the differential diagnosis of these two conditions,”  Alesci said, noting that this research coud eventually help identify new treatment approaches for each condition.

The study analyzed blood samples from 160 participants, 80 with gluten sensitivity, 40 with celiac disease and 40 healthy people, all of whom were consuming an unrestricted amount of gluten. Gluten has to be consumed for antibodies to be produced, and currently in the case of celiac disease, for a diagnosis to be made.

Innate immunity: Nonspecific defense mechanisms that come into play immediately or within hours of an antigen’s appearance in the body. These mechanisms include physical barriers such as skin, chemicals in the blood, and immune system cells that attack foreign cells in the body. The innate immune response is activated by chemical properties of the antigen.
Adaptive immunity:An antigen-specific immune response. The adaptive immune response is more complex than the innate. The antigen first must be processed and recognized. Once an antigen has been recognized, the adaptive immune system creates an army of immune cells specifically designed to attack that antigen. Adaptive immunity also includes a “memory” that makes future responses against a specific antigen more efficient.

Researchers do not yet know what results of the study mean for gluten sensitivity as a whole, though indications are that it is the adaptive immune response that is less inflammatory compared to celiac disease. The differences in immune response may have some relevance related to the type and extent of injury to the lining of the intestine in the two conditions, Alaedini said. But he noted that other studies have found that greater prominence of systemic activation of the innate immune system of those with gluten sensitivity. “Taken together, the data show that the two conditions are very different in terms of immunologic mechanisms and pathways involved,” Alaedini said.

Although commercial tests for gluten sensitivity are on the market, there are currently no tests considered to be reliable, leading researchers to continue to search for a biomarker in the blood that can be used to accurately diagnose the condition. Alaedini said he is not aware of any commercial tests on the market that are based on a peer-reviewed or publically available study that is relevant or reliable.

You can read more about the new study here.

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