Bana Jabri, PhD, Professor in Medicine, Pathology and Pediatrics and the Vice Chair for research in the Department of Medicine, trained as a Pediatric Gastroenterologist with a PhD in Immunology, Director of Research at the University of Chicago Celiac Disease Center talks about the research being done towards finding the cause and potentially a cure for celiac disease.
Interview conducted by Ivanhoe Broadcast News in October 2017.
Are you a scientist clinician, do you do both?
Jabri: I don’t see patients but much of my research is transational.
I wanted to start by asking you about celiac disease. Can you explain what it is?
Jabri: Celiac disease is a unique food adverse reaction to gluten. It has a component that would make it resemble allergy to a food and that it is very specifically against gluten which is present in wheat, rye and barley. But on the other hand it resembles a lot of organ specific autoimmune disorders such as Type I Diabetes because you have this tractional, very particular tissue set type which is the surface of the interior lining of the intestine. And those cells are critical for absorbing nutrients. This very specific destruction of one cell type and the genetic makeup that is required for the disease are very close to what one finds for organ specific autoimmune disorders. So you could correlate it with immune like disorder induced by food antigen.
Could tell me a little bit about the symptoms of a patient who has celiac?
Jabri: Actually they’re pleiotropic, you can have everything. The typical description was the little child of three years who has ingested gluten for two years and has the big belly, has stopped growing and is incredibly tiny. But we know nowadays that it can occur at all ages. Symptoms can range from fatigue to even obesity and constipation. You don’t have to have diarrhea to have celiac disease. You can have neurologic symptoms, you can have anemia, you can have issues of infertility. The reach of symptoms are really extremely variable and there’s a big range.
With that wide range of symptoms is there a lot of confusion, is there a lot of misdiagnoses? Is this a hard disease for a doctor to diagnose?
Jabri: It was a very hard disease to diagnose for physicians in the United States and this was for a very simple reason, which is that the medical textbooks only describe celiac disease as occurring in children and being associated with malnutrition and diarrhea. So the medical students were not instructed to look for celiac disease if it occurred in adults, if a patient had these symptoms. But now that people are much more aware of that and in the past ten years there has been a lot of education for the medical community, since then the diagnosis went from ten percent up to fifty or sixty percent of celiac patients. It has dramatically improved just by making doctors aware of the range of symptoms.
Is there a difference between someone saying I have gluten allergies and having celiac disease?
Jabri: Yes, there’s actually a very big difference between what people call gluten sensitivity and celiac disease. Celiac disease is a very well defined disease. It has a very specific genetic association and if you don’t have that genetic risk factor you can almost rule out celiac disease. Secondly there are a set of very specific diagnostic markers that we know and that doctors are using; one of them is antibodies. Finally the typical disease is associated with the destruction of the intestinal lining and so a biopsy shows the presence of what we call villas atrophy. Gluten sensitivity is not defined; there is no clear diagnostic marker it’s really based on patients describing that they’re not doing well when they eat gluten. However, we also know that when individuals eat gluten they also absorb some of particular sugars that can trigger a lot of the symptoms. Until you have very well done studies where it is actually demonstrated that gluten itself causes those symptoms and you actually identify very specific molecule markers that can help for the diagnosis of this disease I think we have to be very, very careful when we talk about this disorder. It’s not a good thing because it creates a lot of confusion for celiac disease which is really a disease that needs to be treated.
Can you speak a little bit to your research, what are you and your colleagues looking to determine?
Jabri: I would say that the research program at the University of Chicago is very particular in that we are looking both at children and adults. We have a fantastic group of clinicians, both in the pediatric area as well as in the adult area. And myself being a pediatric gastroenterologist who has a very strong training in immunology I’m really able to talk both to the physicians as well as to people who do very basic science in different areas, in physics and chemistry and immunology. And we know nowadays that in order to tackle a disease as complex as celiac disease you need a really multi-disciplinary approach. So my laboratory really looks at all aspects; we look at the basic mechanisms that are going to trigger what we call loss of tolerance to gluten. Why do you mount actually an inflammatory destructive immune response when you eat gluten. Knowing that forty percent of population is actually allergic, so we have to look very carefully at what could trigger the disease and promote these inflammatory disorders. Then we are also very much interested in understanding what causes the destruction of the tissue. And so we have worked a lot also on the molecule mechanisms that drive tissue destruction. At the same time we are also involved with the clinician in trying to identify diagnostic markers for celiac disease even in patients who are on a gluten-free diet. I would say our own studies have led to a number of clinical trials and we are also involved in helping develop those clinical trials and also analyzing the data.
Why is it critical for researchers to determine why this happens, and what’s the next step once you know why it happens?
Jabri: It’s important for several reasons. One is that if you understand why it happens you can prevent it. We know now that for instance children who are born in families where celiac disease is present that around twenty to thirty percent of those children will develop celiac disease. Once you have this genetic makeup you are at very, very high risk of developing the disease. If we understand what triggers it, we can start making interventions in these children and prevent actually the development of the disease. And then once you also understand the mechanisms even once the disease has developed you can start thinking about how to target critical checkpoints so that you may be even able to revert and redirect the delititus immune response to gluten and make it a friendly nonaggressive response.
What’s the gold standard treatment for celiac disease now, is it mostly just dietary changes?
Jabri: Yes. The current treatment for celiac disease is gluten-free diet. It is a very important treatment and when patients have not been diagnosed for ten, fifteen years they can suffer tremendously of the disease. But there are a number of morbidities associated with that such as cancer, increased autoimmunity, anemia, osteoporosis so it’s extremely important to treat those patients. But we also know when you look at adult celiac patients that only around fifty percent to sixty percent will recover to an almost normal intestinal lining or normal morphology of the intestine. The rest of the patients will still have signs of inflammation and will still have a number of symptoms that are associated with that. So it’s actually important also to reverse that part of ongoing inflammation. We also know that it is extremely difficult to have a perfect gluten-free diet. Because as soon as you know, you go to social events, you’re going to eat outside there’s no way that you can control and have zero gram gluten input because gluten is present in many, many foods but also in other things including lipsticks and other manufactured goods. So it’s really extremely difficult to have a zero gluten containing diet. And some people are extremely sensitive to even lower amounts of gluten. The fact that you have more than forty percent of adult patients who don’t recover to a complete normal morphology, given the difficulty of this diet, more and more people realize that it is important to have alternative treatments to the gluten free diet or at least adjunct therapy to the gluten free diet.
How close are you and your colleagues to something that will lead to a cure, to a different outcome for these patients?
Jabri: I would say a way to answer your question would be to say that ten years ago there were zero clinical trials and today there are more than five ongoing clinical trials. So it just shows you that the field has tremendously progressed. I think we are still at the beginning but I think that we have very good targets right now and that you know hopefully in the coming fifteen years we will be able to offer something in addition to the gluten-free diet or even in place of the gluten-free diet.
Is there anything I didn’t ask you about your research that you would want people to know?
Jabri: I think it’s important for us to realize that even if you have a very strong genetic makeup it’s not sufficient to have the disease. And like many complex disorders, celiac disease, Type I Diabetes, autoimmune, lupus, you have genetic factors but you also have environmental factors that also could be critical. And so it’s important to understand what they are because again in that case you can intervene. So viral infections have been associated for many years with autoimmune disorders, but there was actually no proof that this could be the case. In collaboration with Terence Dermody who is now the Chairman of Pediatrics at the University of Pittsburgh who is a expert in real virus biology we really developed a experimental program and setting that enabled us to test where the viruses are critical for triggering development of celiac disease. We were able to show that a virus that apparently is harmless that you can clear it, there is no intestinal adhesion, no overt clinical symptoms in the background, can actually confuse your immune system and can initiate an immune response that is inflammatory and destructive targeted against gluten. Because when you ingest it and you have a viral infection now all of a sudden the immune system thinks that gluten is like a virus and mounts this kind of inflammatory immune response. We were able in the mouse model that was looking at celiac disease patients to show that such a virus could actually be a key trigger. It’s important because we don’t think that a real virus infection is the only virus or is the only cause for triggering celiac disease but certainly it is a cause in a quite significant number of subjects. This kind of discovery can then lead to either changing how we introduce gluten, just to give you an example, babies have maternal antibodies. The maternal antibodies disappear on six months of age, that’s the time when you introduce gluten. So if the baby happens to have a viral infection at the time where gluten is being introduced that is when it is at the highest risk of starting to develop an inflammatory immune response. So maybe in the high risk children one should be careful about not combining the introduction of gluten at the time where the maternal antibodies are lost. And then something we’re doing in my laboratory, we’re looking at whether having a vaccine against a real virus could actually prevent this kind of triggering of the disease. One could also again envision that in high risk children one would vaccinate them so as to prevent this kind of viral infection.
What are some of the surprising symptoms of celiac disease that most people wouldn’t think about?
Jabri: One surprising obvious symptom is constipation. You would never think that you could have celiac disease and have constipation. I would say fatigue, and even depression. You would not naturally think that this could be associated. And finally another maybe surprising association is fertility in a woman.
How prevalent is that, the infertility?
Jabri: It’s unclear because one would need to do a number of studies. But there are reports showing that women who couldn’t have children diagnosed with celiac disease going on gluten-free diet were then able to have children.
What happens when people go untreated, if they’re undiagnosed for a long period of time, or go totally untreated for the disease?
Jabri: Patients who are not treated I would say one of the most severe complications are cancer. And there is a particular cancer that’s associated with celiac disease that is called enteropathy-associated T-cell lymphoma which is a very severe lymphoma that is really a complication of untreated celiac disease. It is also known that not treating celiac disease can be associated with osteoporosis. Some people develop neurological symptoms and finally you could have long-term complications, neurological complications. But again I would say the major complication is cancer and osteoporosis and potentially neurological symptoms.
What are some of the top mistakes that people make when they have celiac disease?
Jabri: Maybe one thing that we need to help patients with is understanding what a gluten-free diet is, which is not so obvious. And helping them enjoy a good diet while they are excluding gluten from their diet. I would say not realizing that going on a gluten-free diet is important and that even if you don’t have symptoms when you eat gluten, gluten can actually do a lot of harm.
END OF INTERVIEW
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