Celiac disease is a rare autoimmune illness, where the immune system starts attacking the outer layer of intestine once gluten is ingested. However, people complaining about gastrointestinal problems after gluten consumption far exceed the number of people living with celiac, these are mostly people who cannot digest gluten due to various reasons. Gluten-intolerance may be a milder, but frequent problem that is hard to differentiate from celiac disease in many cases because of the similarities in symptoms.
There are antibody tests for celiac disease. However, these tests are neither 100 percent specific nor sensitive. This means that negative antibody tests would not exclude celiac disease. A biopsy may be more specific, but it is an invasive procedure and costly too. Genetic testing has only little value in practical diagnosis, while challenge tests (that is giving gluten to eat and then see the reaction) would be positive in both conditions (celiac disease and gluten intolerance).Thus researchers are looking for simpler blood tests that could help to differentiate celiac disease with other gastrointestinal disorders including gluten intolerance.
How does the new test work?
Celiac disease is characterized by a specific kind of autoimmune reaction and inflammatory response, something that is not present in gluten sensitivity. In devising new diagnostic blood test, researchers turned their attention to the inflammatory factors.
Cytokines are a group of substances that play an essential role in inflammatory responses. The word "Cytokines" is an umbrella term for a group of compounds performing various functions in our body, and they have a vital role in immunity, immune responses, and inflammation. Investigators found that if they checked the levels of cytokines in blood within 6 hours of ingestion of gluten-rich diet, they could differentiate celiac disease from gluten intolerance, as in celiac disease levels of cytokines would be much higher. Data of this new diagnostic method was presented at UEG (United European Gastroenterology) week.
In the latest investigation, researchers saw that there was an increase in IL-2, IL-8, and IL-10 (all types of cytokines) after ingestion of gluten in a challenge test. Vice versa, they did not see any inflammatory response in those with gluten intolerance, though they did react to the FODMAPs, especially to fructans. FODMAPs stands for Fermentable Oligosaccharides, Disaccharides, Monosaccharides, and Polyols; these are the types of carbohydrates that are difficult to digest by many and often leading to irritable bowel syndrome.
Biotech company ImmusanT is planning to develop a diagnostic kit based on this technology for an early diagnosis and differentiation of celiac disease, something that current diagnostic tests are unable to do, especially in cases when a person follows the strict gluten-free diet.
Although the results of the research surprised the investigator, things were consistent with previous discoveries that ingestion of gluten-rich diet results in an immediate immune response (within 2-4 hours) involving T-cells. Activation of T-cells is characterized by elevation of inflammatory substances, especially cytokines. Nevertheless, untill now there was no method for measuring this immune response, as many investigators thought about other mechanisms behind this immune reaction.
Further, researchers found that in gluten-sensitive groups symptoms were triggered more by FODMAPs rather than gluten, thus providing data on the kind of dietary changes required in those living with non-celiac gluten intolerance. In a non-celiac group, many did not respond to a gluten-rich diet, which is consistent with the earlier findings that many patients are wrongly diagnosed with celiac disease or gluten intolerance when the culprits are FODMAPs.
ImmusanT researchers carried out their investigation in collaboration with the University of Oslo. They wanted to know the sensitivity and specificity of the test. They divided the participants who were on the gluten-free diet for an extended period, into three groups. In the challenge test, one group was given gluten containing breakfast bars, the second group was given FODMAPs, and the third group was given a placebo. They evaluated the levels of IL-2, IL-8, and IL-10 in blood every 2, 4, and 6 hours. There were 19 participants living with celiac disease and 49 patients with non-celiac gluten intolerance.
Gluten-containing bar triggered the T-cell mediated inflammatory response in 12 of the 15 participants evaluated for this. Further, gluten-containing bars triggered a symptomatic response in all those with celiac disease. However, the gluten bar did not trigger any symptom response in gluten intolerance group, though they showed the symptoms of irritable bowel syndrome on consuming FODMAPs.
Further, researchers found that IL-2 was the most sensitive and highly specific predictor in celiac disease, and there was a significant rise in its levels after consuming gluten bars. IL-2 rose by 1.2 times after 2 hours, and it rose 10 times after 4 hours, and at 6 hours it was still 3.6 times higher when compared to the non-celiac gluten intolerant group.
IL-8 and IL-10 were also significantly elevated in the celiac group as compared to the non-celiac group. However, it seems that these markers have lesser diagnostic value since they rose by just 1.2 to 1.8 times after 4 to 6 hours.
The final data analysis demonstrated that IL-2 was 74 percent sensitive and 98 percent specific in diagnosing celiac disease, while IL-8 was 42 percent sensitive and 100 percent specific, and IL-10 was 32 percent sensitive and 100 percent specific. If these three markers are used in combination, they would be able to provide exact results.
These results demonstrated that this test could be a game-changer in the diagnosis of celiac disease in primary care, it would not only help in the right diagnosis, it would also save many from misdiagnosis. Especially in those cases when FODMAP intolerance or irritable bowel syndrome are confused with celiac disease.
Gluten intolerance or FODMAP sensitivity could be 10 percent or more in the general population, while the prevalence of celiac disease is less than 1 percent. So, it is vital to have some simple tests that could assist primary care physicians in differential diagnosis with high specificity. Confirmation of celiac or non-celiac disease would help to prevent the needless hassle of switching to a gluten-free diet for many, where it has no benefit, if not harm.
This test is in the final stages of development. Though, there is still a need for further large-scale trials before it could be commercialized and become available to patients.
- ImmusanT Blood Test Differentiates Celiac from Non-Celiac Patients Through Cytokine Levels. https://www.businesswire.com/news/home/20171101005665/en/ImmusanT-Blood-Test-Differentiates-Celiac-Non-Celiac-Patients. Published November 1, 2017. Accessed February 14, 2018.