Four hours after a gluten food challenge, patients with coeliac disease on a gluten-free diet had a 15-fold increase in a blood cytokine called IL-2. This observation raises the possibility of a rapid blood test for coeliac disease.
is caused by an immune reaction to gluten, a protein found in foods made from wheat, barley, rye and oats, that damages the lining of the intestine. Because it can cause a wide range of symptoms, including nausea, vomiting, abdominal pain and diarrhea, the condition can be difficult to diagnose. At present screening for coeliac disease
depends on detecting increased serum antibodies to tissue transglutaminase (tTG) and to endomysium (EMA). The antibody concentrations fall when dietary gluten is low, so for effective screening a normal diet needs to be eaten that contains gluten in more than one meal each day for at least six weeks before testing.
Patients on a gluten-free diet who eat gluten-containing food often experience abdominal symptoms an hour or two later, and it is known that exposure of coeliac tissue in culture to gluten peptides (fragments) releases small protein messengers called cytokines. Research workers from Australia, the USA and Norway have studied the time relationship between symptoms and cytokine release in 19 volunteer coeliac patients who had been on a gluten-free diet for a mean of 10 years. A new multiplex electrochemical luminescence system was used to measure 18 serum cytokines both after the injection of synthetic gluten peptides and after feeding natural gluten. The work was published in Science Advances on 7 August 2019
In the natural gluten challenge part of the study, 11 patients took a wheat flour slurry containing 3 grams of gluten protein and 9 patients took a gluten-free rice flour slurry. All but one of those given wheat showed increases in serum cytokines. The most sensitive cytokine, interleukin-2 (IL-2), peaked after four hours, with an average 15-fold increase. None of those given rice showed any serum cytokine change.
Dr Bob Anderson, a joint senior author of the paper, said “The unpleasant symptoms associated with the disease are linked to an increase in inflammatory molecules in the bloodstream, such as interleukin-2 (IL-2), produced by T-cells of the immune system. This response is similar to what happens when an infection is present, however for people with coeliac disease, gluten is the trigger.”
Associate Professor Jason Tye-Din, head of coeliac research at the Walter and Eliza Hall Institute of Medical Research, Parkville, Australia, said work was now underway to explore the development of a simple blood test for coeliac disease. “For the many people following a gluten-free diet without a formal diagnosis of coeliac disease, all that might be required is a blood test before, and four hours after, a small meal of gluten. This would be a dramatic improvement on the current approach, which requires people to actively consume gluten for at least several weeks.”
Further research should provide information about whether patients suspected to have coeliac disease who are taking a normal gluten-containing diet have a rapid response of blood cytokines (or other inflammatory markers such as C-reactive protein
) to an oral gluten challenge, and the response of patients with other possible diagnoses such as irritable bowel syndrome to the projected test.
Cytokine release and gastrointestinal symptoms after gluten challenge in celiac disease. Science Advances