About the Study:
Recently, the National Foundation for Celiac Awareness (NFCA) had the pleasure of connecting with Dr. Asbjorn Christophersen, MD, PhD, on his contribution to a recent study on a new diagnostic test for celiac disease.
A celiac disease diagnosis is an extensive and invasive process that can take years to get right. The research team of Professor Ludvig Sollid at the University of Oslo, a NFCA Scientific/Medical Advisory Council member, has developed a new blood test that makes diagnosis much simpler.
When gluten is ingested by a person with celiac disease, their immune system mistakes it for a bacteria or virus, therefore attacking the gluten protein and inflaming the small intestine. A person’s T cells are responsible for sending this message to attack, as they are reactive to gluten.
This new test works to identify the gluten-reactive T cells in the blood. People with celiac disease have much higher levels of these T cells, and this blood test will allow detection of the disease even if a person has gone gluten-free.
While not available today, if future clinical trials are successful, this new blood test would have the potential to be completed at a general practitioner’s office.
So, What Does This Mean?
Diagnosing celiac disease has the possibility of becoming a lot easier in the near future. With the creation of this new blood test, the gluten challenge (purposeful consumption of gluten after going gluten-free in order to be clinically diagnosed) will be no longer!
Today, many people with celiac disease are self-diagnosed and start the gluten-free diet on their own. This is one of the biggest challenges in the field, for patients, physicians and researchers. Once a celiac disease patient goes gluten-free, the damage to their small intestine starts to reverse. This makes diagnosis from a medical provider difficult because a person must have gluten in their system to be diagnosed accurately. Self-diagnosis is not a suitable option for patients, as celiac disease requires lifelong follow up with physicians and registered dietitians, regular blood tests, nutritional labs and testing for other associated conditions. Because this blood test can detect gluten-reactive T cells without the consumption of gluten, the undiagnosed population will not have to deal with the discomfort that comes along with the gluten challenge. Further research is necessary in order to finalize this simplified method of diagnosis, and this test in not currently available for the public.
Q. What are the main differences between this blood test and the blood tests that are currently being used to test for and diagnose celiac disease, especially the IgA-tTG (tissue transglutaminase)?
A.With the current blood test, we detect the cells that recognize gluten and not antibodies. The antibody tests (like IgA-tTG) and the gut biopsy test (analyzing disease-specific alterations in the gut) are not sensitive enough to detect celiac disease in individuals on a gluten-free diet since the damage begins to correct itself once gluten has been removed. The new blood test we have developed lets us detect the disease also in individuals on a gluten-free diet. Thus, our test works independently of the gluten content in the food of the patient.
Q. How is this test able to recognize that a person has celiac disease regardless of whether they have been eating gluten?
A. The cells we detect are gluten-reactive CD4+ T cells. They are present in the gut and in the blood of celiac disease patients and they are responsible for the inappropriate recognition of gluten that causes celiac disease. The number of such cells decreases in blood when celiac disease patients adhere to a gluten-free diet. However, by the use of specific staining that we have developed in the lab of Ludvig Sollid, PhD, NFCA Scientific/Medical Advisory Council member, and through an additional method using small magnetic beads armed with antibodies to the staining reagents, we have found a way to detect these cells in people with celiac disease. That’s because they occur at higher numbers in celiac disease patients than in healthy individuals, even when they stay on a gluten-free diet.
Additional information: To answer why gluten-reactive CD4+ T cells are still elevated in patients on a gluten-free diet is not straight forward. It may be explained by the fact that celiac disease patients have started an immune response against gluten. The gluten-reactive T cells have been going through several cell divisions (proliferation) as part of the immune response. To some part, that can explain the increased number of such cells in the celiac disease patients (including those on a gluten-free diet). From what we have studied so far, healthy controls (people without celiac disease) do not mount a cell response to gluten - at least not to those pieces of gluten that initiate the immune response in celiac disease. That is why we barely find signs on gluten-reactive T cells in the blood of healthy individuals and why they are totally absent in the gut of healthy individuals. In addition, the gluten-reactive blood T cells in celiac disease patients on a gluten-free diet are probably long-lived memory cells that circulate in the body ready to initiate an immune response in case of new exposures to gluten. It may also be that the number is increased even though patients are on a gluten-free diet because they are exposed to small amounts of gluten in the foods that activate the gluten-reactive T cells to some part.
Q. What type of benefit will this blood test have for people who are already diagnosed or those who have gone gluten-free and are looking to be diagnosed? Are there any other specific patient populations that may benefit?
A. If this becomes available it will primarily benefit those who have gone gluten-free without an official or proper diagnosis of celiac disease made by a medical provider. These individuals will not have to go through a gluten challenge for weeks or months before the diagnostic tests can be initiated. The test will not directly benefit those that have already been diagnosed.
Q. Compared to the way doctors currently diagnose celiac disease (using an anti-tTG blood test and a small intestinal biopsy), what are the benefits of being tested this way? Will this blood test be used to confirm a diagnosis of celiac disease or will a biopsy still be necessary?
A. The results we have so far strongly indicate that gut biopsies will not be necessary to diagnose the disease and that our method can work as a stand-alone test. Alternatively, if both the antibody test (e.g. IgA-tTG) and our test are positive, gut biopsies will most likely not be necessary. Accordingly, general practitioners may perform the final testing to confirm a diagnosis without referring to a specialist (a gastroenterologist for gut biopsies) as they send blood samples for analysis to a central laboratory. Such a diagnostic approach would be much more convenient for the patient and it may also save money.
On the other hand, diagnosis through gut biopsies is very well established and often wanted to also exclude other diseases.
Q. Will this blood test have an impact on the gluten challenge?
A. Our method will make gluten challenge unnecessary in most cases.
Q. Since this blood test is not yet publicly available for use in the doctor’s office, what next steps are you and your research team taking? When would you expect the test to be ready for use in clinics?
A. We are currently running a large clinical trial to confirm the initial findings. The trial will be completed within 2016. To bring the test to the market will need the involvement of commercial companies, and we are currently in touch with a company that is interested in taking such a role. It is difficult to predict when that may happen, but it will at least take three years, probably more.
Q. What, if any, role can diagnosed patients and their family members play in this research process?
A. We will need a great number of blood samples from both celiac disease patients and healthy individuals to confirm the initial research findings and to try to improve the original test in the years to come.
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