The Changing Face of Celiac Disease


Q&A with celiac expert Stefano Guandalini, MD.

Stefano Guandalini, MD, is an internationally recognized expert on celiac disease who has greatly influenced the way the condition is diagnosed and treated. He founded the University of Chicago Celiac Disease Center in 2001, where he’s served as medical director, as well as section chief of Pediatric Gastroenterology, Hepatology and Nutrition at the University of Chicago Medicine. He recently transitioned from these positions to the role of professor emeritus.

In recognition of his multiple contributions and as part of Gluten Free & More’s 20th anniversary, we asked Dr. Guandalini about the past and the future of celiac disease research and treatment.

Stefano Guandalini

Q: When did you first come to the University of Chicago? What was the need at that time?

Dr. Guandalini:  I came to the University of Chicago in 1996. In Italy, I left a population of several hundred celiac patients. When I joined the section of pediatric GI here, I was surprised to see that they only had a couple handfuls of celiac patients. But they had many, many hundreds of patients with inflammatory bowel disease. The awareness of celiac disease and the many ways it might present was just not there.

That gave me the impetus to try and change something here. I thought the best way to do this would be to create a pool of people within this institution who would share an interest in this condition and begin educating medical students, start spreading the word at conferences and get our pediatrician colleagues in primary care to check their patients for celiac disease.

Q: What’s changed in our understanding of celiac disease since that time?

Dr. Guandalini:  A lot has changed. The discovery of tissue transglutaminase (tTG) as the autoantigen for celiac disease is actually a fairly recent finding—it occurred in 1997. Up until then, we really didn’t know that celiac disease was an autoimmune condition. This was a dramatic paradigm shift. Still today, it is the only autoimmune condition for which we know the environmental trigger, which is gluten, of course, and the autoantigen, which is tTG. A couple years later, the finding of tTG antibodies was really seminal, as it provided us with a sensitive and specific marker for celiac disease.

Also, the prevalence of celiac disease is increasing. We have blood samples from the late 1940s that show us that the prevalence of celiac disease at that time in the United States was much lower than it is now. Several studies in the last 10 years or so have shown that there has been a substantial increasing prevalence of celiac disease.

The presentation of celiac disease has changed substantially over time. Initially, it was thought of as a disease characterized by malabsorption. The big belly, weight loss, chronic diarrhea—this was the way celiac disease would present in the mind of every physician. In the late ’80s and early ’90s, people in Europe had begun to show that the pattern of presentation of celiac disease was changing, moving toward a little older age and from intestinal to extraintestinal manifestations. People began to realize that celiac was associated with dermatitis herpetiformis, anemia, headaches, short stature, delayed puberty, elevated liver enzymes, arthritis. These weren’t on the radar when people thought about celiac disease—and now they are.

The change in the way celiac disease is diagnosed has been a great success. About six years ago, the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) promoted new evidence-based guidelines for the diagnosis of celiac in children and teenagers. If you have a child suspected of celiac who has very high tTG antibodies and clearly positive anti-endomysial antibodies (EMA), this child can be diagnosed with celiac disease without undergoing a biopsy.

The other big change in the past 20 years in the United States has been the increase in awareness, the increase in medical education. I see a lot of children now being screened for celiac disease for the right reasons. The pattern of understanding and thinking about celiac disease by the primary care pediatrician has changed dramatically—for the better.

Q: Can you talk about the changes in ways we might be able to diagnose celiac disease for those who have already gone gluten-free?

Dr. Guandalini:  We’ve known for a long time that there are some lymphocytes, some T cells, in the gut called gamma/delta lymphocytes that can be detected and measured with biopsy. These gamma/delta lymphocytes are active and detected only in people who have celiac disease who’ve been on gluten in the past. That’s relatively low-hanging fruit [in terms of a test to detect celiac disease] that people for some reason have neglected and this method isn’t used.

And very recently, scientists in Oslo reported on a new test based on the detection of gluten-specific T cells in the blood of patients with celiac disease, even if they are on a gluten-free diet. This test, which needs to be validated in a larger study, would allow individuals with suspected celiac disease to avoid a gluten challenge and duodenal biopsy.

Q: What’s the role of the microbiome in celiac disease?

Dr. Guandalini:  There’s now a clear understanding that the microbiota play a very important role in the development and maintenance of our immune system, specifically with the gut immune system. This means the microbiota has a role in many conditions, including Crohn’s disease, ulcerative colitis and certainly celiac disease.

However, a lot of work still has to be done. The problem is that we have about 300 trillion bacteria living in our gut. There are more than 500 species and about 100 haven’t even been characterized and named yet. We’re just beginning to dig into this goldmine, but it’s clear that there’s going to be some microbial signature in infants and toddlers that’s either protective or fails to protect when it comes to the development of autoimmune conditions, including celiac disease.

Q: Can probiotics be helpful?

Dr. Guandalini:  There’s not a lot of evidence that probiotics can be helpful in somebody who has celiac and is following the gluten-free diet, because strictly following the diet—although not easy—restores intestinal health in the majority of patients, especially the young ones. Once we know exactly what kind of microbiota you need to have in your gut to be helpful against celiac disease, the next step would be to devise the right probiotics.

Q: Where is research heading in ways to treat or possibly prevent celiac disease?

Dr. Guandalini:  There’s clearly a need to have alternative treatments to the gluten-free diet. People are actively trying to work on treatment alternatives. There are several strategies. One is to quench the pro-inflammatory cytokines like IL-15 that are involved in maintaining active inflammation in the intestine.

Also, if you can block the tTG at some point during the cascade of events that gluten triggers, you might be able to block the whole immune response. The problem is that tTG is an enzyme that Mother Nature gave us because it’s useful. It’s not there to cause you to develop celiac. If you block it, you need to be able to block it only when it’s in its active state and only when it’s in the intestine. So it’s not an easy task but there are centers that are actively working on this.

There is the therapeutic vaccine that Dr. Bob Anderson [chief scientific officer of ImmusanT] in Boston is working on. He has identified the epitopes or toxic fragments of gluten components. The strategy is to inject small amounts of this epitope subcutaneously with progressive doses in patients who already have celiac disease in order to restore their tolerance to gluten. This approach is similar to environmental allergy desensitization shots. They’re about to launch a multicenter study in adults to see whether this therapeutic vaccine would work, so that’s very promising.

passage of time

© gorsh13/Istock/getty images plus

Last but not least, Dr. Bana Jabri [director of research at the University of Chicago Celiac Disease Center] recently found that there’s a virus, called reovirus, which is an innocuous kind of virus that many people get. She has shown in animal as well as human-derived samples that this virus is able to create a pro-inflammatory environment that might lead to celiac disease if you have the right genes. If this reovirus actually causes celiac disease in a subset of patients, you could develop a vaccine against it and immunize babies, perhaps preventing a number of people from developing celiac.

Q: Looking to the future, what do you see?

Dr. Guandalini:  In the future, I think we’re going to have a way of curing celiac disease without relying on the diet. There are several forms of pills that either are beginning to appear or will appear shortly that will allow celiac patients to eat some gluten—they detoxify the gluten while in the stomach. It’s not a cure for celiac disease, because it doesn’t treat it; it simply prevents gluten already ingested from being harmful.

Hopefully, as mentioned, a therapeutic vaccine will be a game-changing proposition. And finally, maybe we’ll identify what probiotics we need to give to which babies in order to prevent celiac disease. It’s not for me to discover but for the new generation, who we have hopefully been able to attract to this exciting field.

Q: What’s next for you? The beach? The golf course?

Dr. Guandalini:  No, I’m not a golfer. Next for me is spending more time with family—with my wife and kids and especially my grandchildren whom I, of course, adore. Spending more time with my three cats, cooking more and traveling, which is also a way of enjoying my passion for photography. And of course, still being involved as much as I can in this role. I’m not ready to give it up completely, but I’m ready to give up the stress—yes, that I am.

Eve Becker is associate editor of Gluten Free & More magazine.


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