Vanessa Weisbrod: Welcome to season two of Raising Celiac, a podcast dedicated to raising the standard of education, awareness, and research on celiac disease and related autoimmune conditions. We have some exciting changes for this season. The Boston Children’s Hospital Celiac program has teamed up with the Celiac Disease Foundation to expand the reach of our educational podcast. Our goal is simple to provide education to as many health providers and patient families as possible. I’m Vanessa WeisbrodBroad and I’ve started a new role as the Chief Education and Community Engagement Officer at the Celiac Disease Foundation. In every episode, you’ll also hear from Janis Arnold, an incredible social worker at Boston Children’s Hospital, who is the voice of our patient stories. Each month on the podcast, we will invite leading experts to dive into a hot topic related to celiac disease and look at how it impacts a patient family, the latest research and offer suggestions for health providers to manage these complex cases. Every episode of the Raising Celiac podcast is accredited by the Boston Children’s Hospital Continuing Education department for physicians, nurses, social workers, dieticians, and psychologists. To claim your credits for listening to today’s episode, please visit DME dot children’s hospital.org/raising celiac. We’ll also drop that link into the show notes. Thank you to the Global Autoimmune Institute and the Celiac Disease Foundation for making this podcast possible. Now let’s get started with this month’s raising Celiac patient story.

 Janis Arnold: Jonah was a 3-year-old marketing professional living in the beautiful mountains just outside of Denver. For years, he struggled with various symptoms that left him feeling exhausted and confused. Nausea, fatigue, and recurring brain fog became his unwelcome companions, but he never connected the dots. Like many others, Jonah thought he was just dealing with stress or a sensitive stomach.

 Vanessa Weisbrod: Nausea, fatigue and brain fog are a common non gastrointestinal symptoms of celiac disease often triggered by gluten exposure. Nausea frequently accompanies acute reactions as the immune system responds to gluten by releasing inflammatory markers, fatigue and brain fog both linked to ongoing inflammation can severely impact daily life and mental clarity for those VA celiac disease.

 Janis Arnold: After a particularly rough week where he experienced debilitating symptoms following a family gathering in northern Italy, Jonah decided it was time to seek medical help. He visited his primary care physician who ran some tests for nutrient deficiencies, all of which came back normal and suggested trying a gluten-free and dairy-free diet to see if his symptoms improved. Eager for relief, Jonah embarked on his gluten-free journey. He decided to cut out gluten first and then move on to dairy because the thought of giving up cheese and milk was too much to bear. At first, it seemed to work. His energy levels increased and his abdominal discomfort lessened. He was able to resume daily runs around a nearby lake. Jonah felt hopeful and believed he had found the answer. However, without a proper diagnosis, his experience

 Vanessa Weisbrod: Was quite incomplete. Starting a gluten-free diet before testing for celiac disease can interfere with obtaining an accurate diagnosis because the immune response to gluten diminishes. Once gluten is removed from the diet without active gluten in the system, blood tests may not show the typical markers and intestinal damage might begin to heal making a biopsy inconclusive. As a result, patients who stop eating gluten prematurely may face a longer, more complicated process to confirm or rule out celiac disease.

 Janis Arnold: Months later, Jonah attended a gluten-free expo in the city where he learned more about celiac disease and the importance of proper testing. Intrigued. He spoke with a doctor who was a speaker at the event who recommended that he start a gluten challenge so that accurate testing could be done to determine if he truly had celiac disease. Jonah wanted to know if he really had celiac disease, so he scheduled an appointment with his gastroenterologist to discuss a gluten challenge. Further, what he learned was shocking. He would need to eat gluten for at least eight weeks before the doctor would run the tests.

 Vanessa Weisbrod: The current protocol for a gluten challenge to diagnose celiac disease involves reintroducing gluten into the diet in order to provoke an immune response. Typically, patients are advised to consume three to six grams of gluten per day, which is equivalent to about two slices of bread for a minimum of six to 12 weeks before ordering serology and biopsy to confirm celiac disease.

 Janis Arnold: Despite his determination to get an accurate diagnosis, Jonah found the task of eating gluten daily, overwhelming. He could barely handle the symptoms he had already experienced after just three weeks of eating gluten. Again, his body rebelled and he ultimately gave up due to the severe symptoms that returned. It was a stark reminder of his previous struggles and left him feeling frustrated and disheartened. He just couldn’t wrap his head around why doctors can diagnose thousands of conditions with one simple blood test, but to get diagnosed with celiac disease, he had to devastate his body for two months.

 Vanessa Weisbrod: Potential to Use IL-2 for Celiac Diagnosis Undergoing a gluten challenge is extraordinarily difficult for many patients and far too many give up before they cross the finish line. But what if there were an easier way? What if it only took eating gluten one time? Or what if doctors could mix a patient’s blood with gluten to confirm a celiac diagnosis? We’ll discuss this and more on today’s episode of Raising Celiac. Today we talk about the future of celiac disease diagnosis using interleukin two with Dr. Jason Tyin, an adult gastroenterologist from Melbourne Australia who leads groundbreaking research on celiac disease at the Walter and Eliza Hall Institute. Dr. Titan focuses on understanding how the immune system responds to gluten aiming to improve diagnosis and treatment for those living with celiac disease. He also runs a specialized celiac disease clinic at the Royal Melbourne Hospital where he works to raise awareness and promote best practices for managing the condition. We’re excited to have him share his insights with us today. Welcome Dr. Tye-Din in to raising celiac.

 Dr. Tye-Din: Thanks so much for having me Vanessa.

 Vanessa Weisbrod: So to get started, can you explain the role of interleukin two in the immune system and why it’s gaining attention in celiac disease research?

 Dr. Tye-Din: Yes, of course. So interleukin two is a chemical messenger in our body. It’s a chemical called a cytokine, and cytokines play an important role in how our immune system functions and essentially they’re tiny little proteins that communicate between cells and basically tell us how our immune system should respond to infections and other threats coming from outside the body. In celiac disease, we’ve shown that actually interleukin two are really important cytokine because when people with celiac disease are exposed to gluten, their immune system and in particular type of cell called a T-cell, starts producing a lot of interleukin two. So we can actually track the immune response in people with celiac disease by measuring interleukin two.

 Vanessa Weisbrod: That is very cool. So can you tell us about the research that led to identifying IL two as a potential biomarker for celiac disease?

 Dr. Tye-Din: Yes, of course. So there was a clinical study of a possible treatment for celiac disease several years ago. It was called NAX two, and this was a drug trying to induce immune tolerance to celiac disease. It was led by a doctor called Dr. Bob Anderson and he was taking forward this particular drug to try to treat people with celiac disease. And during the studies they noticed that people after the injection of NAX two had a range of cytokines in their bloodstream several hours after being injected with the main one being interleukin two. So we thought, this is a very interesting observation, what happens if someone with celiac disease actually consumes gluten? So we went on to do studies to get a whole range of people with celiac disease, have some gluten, and then measure the interleukin two in their bloodstream. And lo and behold, we could see that there was this very prominent increase in interleukin two at very low levels, but still a very substantial increase at around two hours it would start to increase and peak at around three to four hours after the ingestion of gluten and then it would drop away.

 Dr. Tye-Din: So this signal was really first identified in that clinical trial, but subsequently there’s been a whole range of studies both initially in Australia and in Oslo, in Norway, but they’re now replicated around the world including some really good US studies, and it shows that people with celiac disease when they consume gluten, have this interleukin two signal in their blood hours after they consume it.

 Vanessa Weisbrod: That’s so interesting and something that I’ve always people wanting to participate in clinical trials obviously go in hoping that there’s going to be a magic cure that comes out of it. And as we all know, that’s not always the case that many of these trials fail, but there are still really important things that researchers learn from these trials. It’s not just that the drug fails and it all goes away, but that potential new diagnostics and understanding of the disease can actually happen.

 Dr. Tye-Din: Yeah, that’s such a good point. And I think that science and medicines, it’s an incremental journey and we learned things step by step and for that, for example, in that trial I mentioned you’re quite right, that particular drug wasn’t successful, but there was so much learned from the trial that is now informing how we develop and test new drugs. So for example, the interleukin two that was discovered is shaping up to be a very, very useful biomarker, so a way to measure responses and it’s now being used in a range of new trials for new drugs, for celiac disease and helping us understand how those drugs are working. So it’s been a really, really good outcome from that trial to learn about this interleukin two signal.

 Vanessa Weisbrod: That’s great. So have previous studies looking at gluten challenges. Were there any correlations between IL two levels and the severity of symptoms in celiac patients?

 Dr. Tye-Din: Yeah, this is a really interesting point. That’s when people with celiac disease eat gluten. We know that many of them will develop symptoms, not all though interestingly, maybe about 20% don’t get symptoms after being exposed to gluten. But there are people who can get mild symptoms like tummy upset or headaches, brain fog, G lethargy, and the acute ones tend to be things like nausea and vomiting, bloating and tummy pain, but then that can be all the way through to very severe symptoms. So there’s a broad range, and what was striking is that the interleukin two level associates very closely with the severity of people’s symptoms. So for example, if a person developed vomiting after having gluten exposure, then we would typically see a very high interleukin two level. If a person had milder symptoms, then the value tends to be lower. So this was the first time we’ve been able to discover what we call a biomarker for symptoms caused by gluten in people with celiac disease. And obviously that’s very useful because it allows us to track a very subjective symptom and so we can now understand when people have symptoms whether this is likely to be caused by gluten and also just sort of understand hopefully in the future, the mechanisms of why symptoms are happening in response to gluten. So the interleukin two signal is shaping up to also be this kind of symptom biomarker.

 Vanessa Weisbrod: Does the IL two level rise in all patients with celiac disease or does it matter which HLA gene they might carry?

 Dr. Tye-Din: Yeah, that’s a great question. So it elevates in the vast majority of people with celiac disease and you have to use this ultra-sensitive equipment to measure the values because if you don’t, you won’t pick up the signal. But when you use the ultrasensitive cytokine detection tools, you can detect it in well over 95% of people with celiac disease if they eat gluten. And most of the people studied in our various trials have been the common celiac gene type, which is HLA DQ two, and that’s seen in the majority of people with celiac disease. But we do know there are other gene types such as HLA DQ eight or HLA DQ 2.2, and we have less data on those people. And it does seem that the elevation of interleukin two may be different between the HLA genotypes and the most sensitive data comes from HLA DQ two people. In HLA DQ eight, we were showing that it was as not as good at detecting celiac disease signals. So I think we need to understand that a bit more.

 Vanessa Weisbrod: Absolutely. So how could measuring IL two levels change the diagnostic landscape for celiac disease, and what advantages does it offer over current procedures like the biopsy?

 Dr. Tye-Din: Yeah, so as we heard from Jonah’s case, one of the big challenges with celiac disease diagnosis is if you’ve gone gluten-free, it’s enormously difficult to then get tested for celiac disease because the blood tests, the antibody tests or celiac serology is no longer accurate. And the biopsies we use to confirm the diagnosis are not necessarily accurate, particularly if the person’s been gluten-free for several months or longer. So that’s a really big challenge. And one of the things we wanted to do was say, well look, how can we diagnose celiac disease simply and accurately without asking people to go back onto eating gluten for weeks and weeks, which we all know is very, very difficult. It’s going to make people sick and they just can’t sustain that. And we know that celiac disease is caused ultimately by the gluten specific T-cell. So if we sort of drill down, it’s not something in the gut, it’s not something that is related to that.

 Dr. Tye-Din: It’s more related to the immune system. And ultimately if we can detect the gluten specific T cell, which is only really present in people with celiac disease, then we have a good way to diagnose celiac disease. But to date, we’ve not had a good way to detect the gluten specific T cell. So the interleukin two signal is a really good way to detect the gluten specific T cell, and this offers a new approach. So we hope that this blood test will be able to then detect celiac disease because it can detect the gluten specific T-cell. Now at the moment, the initial studies were looking at people eating a small amount of gluten and then having a blood test four hours later and a small amount of gluten’s better than six weeks or more of gluten. But we wanted to take it one step further. And so the blood test was then adapted into a intu system.

 Dr. Tye-Din: So basically instead of asking people to eat gluten, we put gluten in a test tube with a person’s blood sample and then measure the interleukin two the next day after it’s incubated for 24 hours. So in other words, we’re converting a gluten challenge in a person to a test tube, which is far more preferable for people. They don’t need to eat gluten at all. And what’s really exciting is we’ve been testing this in tube blood test where we get a blood sample from someone with celiac disease, and even when they’re on a gluten-free diets, we can detect those gluten specific T cells and diagnose celiac disease. And the sensitivity is over 97% and the specificity is over 97%. So basically that just tells us it’s very, very good at detecting celiac disease accurately and as good as the current blood tests, but obviously the current blood tests require people to be eating gluten.

 Dr. Tye-Din: So I know I just said a lot in that response there, but in a nutshell, I guess it’s telling us that this new blood test can be performed on people even when they’re gluten free and can detect the presence of celiac disease with really high accuracy, which is super exciting. And we have now studied over 150 people and we’re about to hopefully publish all of that data in a medical journal. As we alluded to before, we’ve mostly studied people with the HLA DQ two gene, and we need to study more people with some of the rarer gene types to see how the blood test performs in those groups. And we also need to study children because that would be the next really, really exciting application for the technology.

 Vanessa Weisbrod: I was diagnosed 20 years, four months and one day ago with celiac disease, and I was diagnosed by my primary care doctor who ran the TTG panel and it was very, very, very positive and told me to see a gastroenterologist and I made an appointment for three months later and they’re like, okay, but you’ve stopped eating gluten, so now you have to eat gluten again to do the biopsy. And so I did. I was that person who went back on gluten for eight weeks before the biopsy and it was not fun, it was miserable and I wouldn’t wish that on anybody having to get an accurate diagnosis, but of course you want the accurate diagnosis and so you do it, but to have the option to not need to do that is so remarkable. And I think something that would really help us get a much better understanding and picture of the real celiac community because we know there’s so many people out there that are just gluten-free because they couldn’t get a test or their doctor didn’t want to test them or they just didn’t do it. So it really is I think, going to be a game changer. So okay, you said that when you mix the gluten with the blood that it sits there for 24 hours before you measure it, but that if you eat the gluten it’s four hours later. So how does that work? When is the spike in the blood if you don’t eat the gluten?

 Dr. Tye-Din: Yeah, it’s a really good observation. So when people with celiac disease eat gluten, clearly the gluten’s triggering an immune response and it takes some time for the gluten in the tummy to get into the small bowel and presumably trigger all the immune cells. But four hours is still very fast. And it’s because in celiac disease we know that people have these gluten specific T cells and they’ve got this kind of memory capacity. So they remember that gluten is something they react to. So unfortunately for people with celiac disease, the presence of these cells means that as soon as gluten comes into contact with them, they start getting activated. And interleukin two is one of the major signals of these T cells getting activated. So that’s why we can detect the signal very early on after gluten exposure. And that would be in keeping with the fact that most people who get bad symptoms to gluten usually suffer them within a couple of hours, not minutes.

 Dr. Tye-Din: We know that that doesn’t happen within minutes. That’s more like an allergy, but if you’re developing symptoms after an hour or two, then that’s more in keeping with agg gluten induced symptoms. But when we take blood out of a person and they haven’t eaten any gluten and they have celiac disease and we put it in a test tube with some gluten, the number of cells that are related to celiac disease, the gluten specific T cells is very low. So in a formula tube of blood, you might only have one or two cells floating around that are gluten specific that are the cause of celiac disease. So that’s why when you add gluten to it, you need to let it sit there long enough. So the signal of the interleukin twos big enough for us to measure. So overnight we put it into an incubator and the next day we will be able to test the blood for that interleukin two signal.

 Vanessa Weisbrod: Very interesting. Thank you for explaining that. Okay, so my husband, we don’t think he has celiac disease, he eats gluten normally. If you gave him the IL two test and he did have celiac, would it work to detect it or would he have had to have been gluten-free?

 Dr. Tye-Din: Oh, great question, Vanessa. We have tested people who have active disease. In other words, they’re just coming for their gastroscopy because they’ve been told, oh, you’ve got positive celiac antibody tests, you need a gastroscopy to confirm the diagnosis. So they come into hospital and we say, Hey, can we take some blood and tissue for this new test? And we show that it works. Even in those people who are eating gluten, the signals are a bit lower than people with on gluten-free diet, which is kind of a bit paradoxic. You’d think the signals are higher when people are actively eating gluten. But when we take the cells out of the body, when people are actively eating gluten there, they’re kind of a little bit sort of stunned and they don’t react as much. But yes, it still would work in your husband’s case if we were to test him now and if it was positive, we’d be saying, oh, looks like your whole family’s going.

 Vanessa Weisbrod: We won’t put him through that quite yet. So as you mentioned, symptom severity peaked in lots of these studies around three hours after gluten ingestion. Does that correlate with the timing of IL two release?

 Dr. Tye-Din: Yeah, that’s a great question. Absolutely. So what we see is the IL two starts to go up around the two or three hour mark and then peaks at four hours and then is coming down by six. And so the symptoms that develop seem to sort of follow that fairly closely, maybe a little bit delayed, which makes sense because we believe that the interleukin two is the trigger for symptoms. And in fact, that’s a big research project of ours now is to work out well, how does the interleukin two cytokine trigger symptoms in some people? And it’s quite remarkable. We see that some people are vomiting and quite unwell, and that’s obviously really unpleasant for them. But then some people are sitting there fairly comfortably after a amount a serve of gluten even though they do have celiac disease. So we want to understand why because the interleukin two signal goes up in everyone, but why do only some people get symptoms? So yes, it tracks very closely with symptoms, but also we believe it will tell us more about what’s actually happening in the bodies of people to cause the symptoms themselves. And perhaps blocking interleukin two or some of the downstream chemicals like serotonin or those other things may be really important in helping people overcome these symptoms to gluten.

 Vanessa Weisbrod: Could somebody have the IL two spike within that four hour window but still experience diarrhea, other GI bloating symptoms later?

 Dr. Tye-Din: Yes, great question because that’s something that we do see is that the IL two signal does come up in a fairly defined window, but people’s symptoms are not always within a few hours and you will speak to people where the symptoms are delayed and they will go home and that night get some diarrhea. So I think that whatever’s happening, symptoms are a really kind of variable type of manifestation. Some people get bloating, diarrhea, some people get pain. And so I think there’s a fairly complex pathway once the immune system’s activated, and that must vary between people we dub to understand what’s going on in their bodies to account for that variability. But you’re completely right. Symptoms can be but delayed, but we’d still get that interleukin two signal early on.

 Vanessa Weisbrod: My mom also has celiac disease. She was diagnosed about 10 years before me, and it’s so interesting that her symptoms, my symptoms and my son’s symptoms are all somewhat different, but my mom and son all within two hours, they’re both very sick and me, it’s usually a little bit later.

 Dr. Tye-Din: It’s uncanny. I mean this sounds a bit perverse, but our research program, and I’ve been doing celiac research for about just over 20 years now, and we do do a lot of gluten challenges in order to study immune responses. And the number of people who say that symptoms come on at the two hour mark on the.is quite uncanny. And so they can almost say, I’m going to be sick exactly at 11:00 AM I ate the gluten at night, and lo and behold, at 11:00 AM they’re unwell. So yes, you’re right. I mean I think people are all different, but there are some sort of recurring themes.

 Vanessa Weisbrod: Absolutely. So interestingly, IL two levels remain normal in some patients in these studies, despite them reporting symptoms. What does this indicate about their immune response in these individuals and how might this impact diagnosis? Is it possible that they didn’t really have celiac disease in the first place?

 Dr. Tye-Din: Yeah, yeah, really interesting. So in one of our studies which we published, we looked at people with this interleukin two signal in their bloodstream, and there were a couple of people who didn’t get it, and we believe they had celiac disease and everyone else did. And we thought, well, this is odd, what’s going on here? So we went back to the drawing board with those individuals, and it turned out in these two individuals, they never had positive celiac antibodies for their diagnosis. It was just based on a biopsy of their bowel that showed the villous atrophy. So the doctor assumed, oh, it’s celiac disease because you have villous atrophy. We went back to give gluon to those people for several months, like a long time, and they did not have villous atrophy at the end of that period, and they did not have positive celiac antibodies and they were feeling well.

 Dr. Tye-Din: And so they never probably had celiac disease to begin with, which was really, really quite striking great for them because we undiagnosed their celiac. But it also tells us that we have to be very careful when we make the diagnosis of celiac disease in my clinical practice. So in addition to research, I do see patients as well. When I see a patient who’s been diagnosed based on the small bowel biopsy alone and never had celiac antibody testing or had negative celiac antibody testing at diagnosis, that’s a bit of a red flag for me to say, well, look, I better check and make sure they truly do have celiac disease. Because what we do know now is that the villous atrophy of celiac disease can be caused by other things. It can be caused by medications, it can be caused by infections, chiia, a whole range of other things that can cause it.

 Dr. Tye-Din: So we believe that those two people who didn’t have the IL two rise, even though we thought they had celiac disease, were probably misdiagnosed because they had other things in their past and one probably had giardia infection based on her story. And the other one, it may have been a medication that had caused the villus atrophy to fool the doctor’s into thinking they had celiac. So I do think that there are some cases of misdiagnosed celiac that account for negative results. But having said that, there were some people where we truly believe they had celiac disease and they still had a negative result. We’re still looking into that. Why can we not detect IL two interleukin two in a hundred percent of people? And maybe it’s a timing thing, maybe we need to measure beyond four hours or something like that in that individual, maybe the signal needs to be boosted and maybe they’ve just had gluten recently and released their IL two and we need to sort of wait a little bit or something. So there’s a few tweaks and things to this, but the hope is that we can improve it even further, but the way it performs now is just as good, if not better than the existing CELIA antibody tests, but with the benefit of working when people are free.

 Vanessa Weisbrod: That’s great. So if IL two is validated as a reliable biomarker, how could the diagnostic process for celiac disease be streamlined? I mean, obviously it would reduce the need for the prolonged gluten challenge, but could it ultimately reduce the need for the biopsy?

 Dr. Tye-Din: Yeah, that’s a really good question, and I think we need studies to help us get that data to tell us it can. I mean, that would be the hope. If you’ve got a way to detect the gluten specific T-cell accurately and sensitively, do you even need a small bowel biopsy and perhaps not. And one reason I say that is because as many of the listeners will know that in the last few years, the diagnostic guidelines for celiac disease have been evolving in children. And European diagnostic guidelines in 2020 came out with this non biopsy approach that if the transglutaminase antibody level was very highly elevated, greater than 10 times upper limit of normal, and a second blood test was also positive, then a pediatric gastroenterologist could diagnose celiac disease without needing a biopsy at all. So there’s this slow acceptance that in certain circumstances you can diagnose celiac disease based on a blood test alone.

 Dr. Tye-Din: The hope would be in the future if we can confirm that this interleukin two test is accurate, then if it was positive, I think the field would probably accept that you don’t need to then do a biopsy. So obviously the studies need to be done to confirm that, but that would be the hope. And then you could imagine a time when the blood test was all that’s required and whether you screen people with the transglutaminase antibody test like it’s currently done and then confirm the diagnosis with the interleukin two test, or you just do the interleukin test. I don’t have the answer for that. And again, I think we need studies to sort of model these things and work it out, but I think it’s very nice to have a test that could allow people to avoid a gastroscopy altogether and avoid being on large amounts of G. And I think that’s going to be really good for patients and help reduce a lot of the burden of diagnosis and speed things up. Because I think for me, getting the diagnosis of my patients who have it sooner rather than later is so much better. The delayed diagnosis can be really problematic for people.

 Vanessa Weisbrod: And even just, I’m thinking about a neighbor of ours whose child had a positive TTG blood test four weeks ago, and it’s now, it’ll have been almost seven weeks before they even get in to see the gastroenterologist to set a plan for the next step and then await for the biopsy. So it’s a very long process right now even just to get to discuss a positive TTG test.

 Dr. Tye-Din: Oh, I agree. And I think it’s difficult because as a parent, you don’t want to be seeing your child sick and the answer’s probably staring you right in the face, which is a gluten-free diet, but then you’ve been told, don’t go gluten-free because your daughter or your son may need a gastroscopy. It’s awful. And I’m married to a celiac and our son is HLA gene at risk for celiac, and when he gets symptoms, we do screen him for celiac disease. And I’m lucky, I’m one of the fortunate ones that I can expedite these things, but I do know of a lot of people who’ve waited, and you mentioned three months for you, and I dunno if that’s because you didn’t realize the importance or you just had to wait for a doctor before you could get a gastroscopy. But access to specialists and access to endoscopies is not great around the world, not just the US but other areas. And so I think cheaper technology that’s accurate, that allows a diagnosis to be made sooner is so important for us.

 Vanessa Weisbrod: Absolutely. And the cost piece of it too, there’s so many families, like we see in the United States, about 25% of families with a child with celiac disease can’t afford the gluten-free diet. And we talk about the cost of food, the cost of the biopsy is extraordinary. I mean, it’s not cheap to have that test done.

 Dr. Tye-Din: Yeah. And for children, there’s sometimes a general anesthetic given for adults. It’s a day off work, it’s inconvenient. And there’s the cost factor, as you mentioned. It’s a fairly safe, like the risk of the procedure isn’t high or anything, but it is inconvenient. So alternative, simpler, accurate methods are really needed.

 Vanessa Weisbrod: Absolutely. So Dr. Tye-Din in, what are the next steps in your research on IL two and celiac disease? Are there ongoing studies that patients or practitioners should be aware of?

 Dr. Tye-Din: Yes. So we are hoping to do studies in children, and I’m actually working with some collaborators. For example, there’s Dr. Jocelyn Sylvester in Boston who’s very keen to take forward these trials in children. And I think this is going to be very exciting to sort of confirm that these tools work well in children as a diagnostic test. We are using the tool to measure immune responses to low amounts of gluten. And this is a really exciting area of research where understanding safe thresholds for gluten. So many of your listeners will be aware of 20 parts per million as the threshold for what’s labeled as gluten-free. And I know you’re a bit of an expert in this space too, Vanessa, but the hope is that using this tool, we can measuring people well, when does a certain amount of gluten trigger an immune response that could potentially be harmful?

 Dr. Tye-Din: And this is a lot easier than the traditional approach of feeding people gluten for three months. So that, as you know, there was an earlier study by Dr. Carlo Sasse, which fed people with celiac disease, small amounts of gluten for three months in order to work out whether it was harmful or not. We may have an easier way now with the interleukin two tool, and we’ve been in discussions even with Dr. Carla Potass and other colleagues about studies that incorporate this technology to make it easier, but it will give us a more accurate threshold moving forward with the goal of really ensuring safety for people with celiac disease around the world and safety for people who have to eat gluten free. So that’s the second project. The third project would be using this tool to understand symptoms as we talked about earlier. I think that we know interleukin two goes up, it goes up even higher when people with celiac disease have bad symptoms to gluten.

 Dr. Tye-Din: What is that telling us and what are the mechanisms of the interleukin two causing symptoms? And I really love to be able to develop better ways to treat those bad symptoms because as you know, it can be really disabling. So if we can treat that, that will be really good. And we are working finally with a industry collaborator, Nova Vir, who are really helping to take this forward into the clinic because ultimately this is a tool that I do believe will be useful for patients. And the sooner we can get it out there, the better they can start benefiting. So they’re the ones who are really taking it forward as a package and doing all the relevant steps to really get it all approved and out there. So several things, but it’s sort of really exciting times ahead.

 Vanessa Weisbrod: It is such exciting times and you are doing so much amazing work for this community and just so grateful that you are a part of it. And thank you so much for sharing all of this wisdom with our community today. I learned so much today. I attend all these conferences and I listen to all the talks, but I’ve still always learned something new every time I talk to you. So thank you so much for all of the work that you’re doing and that you will continue to do in this community.

 Dr. Tye-Din: Thanks, Jonah.

 Vanessa Weisbrod: My favorite part of the episode. Let’s find out where our patient Jonah is today.

 Janis Arnold: Nearly a decade later, Jonah is still following a strict gluten-free diet and still has not received a formal Celiac disease diagnosis in his own words, Jonah says, hearing about the future of less invasive diagnostic tests for celiac disease gives me great hope that someday I’ll know if I truly have celiac disease. But until then, I will continue enjoying feeling healthy as long as I don’t eat gluten.

 Vanessa Weisbrod: And now a word from the Global Autoimmune Institute.

 Global Autoimmune Institute: The Global Autoimmune Institute works to empower solutions and the diagnosis and treatment of autoimmune diseases through research, education, and awareness while supporting multidisciplinary approaches to health, we are thrilled to support the production of this educational podcast.

 Vanessa Weisbrod: Thank you for listening to this episode of Raising Celiac. A special thanks to the generous contributions from the Global Autoimmune Institute to make this podcast possible. A reminder to all physicians, nurses, social workers, dieticians, and psychologists to claim your continuing education credits. For listening to today’s episode, please visit DME dot children’s hospital.org/raising celiac. If you like what you heard, be sure to write a review, like and subscribe wherever you get your podcasts. For more information, check us out on social at Boston Children’s Celiac, on TikTok, at Children’s Celiac, on Twitter, or at Celiac Kids Connection on Instagram. Have a great month.

Vanessa Weisbrod:

Welcome to season two of Raising Celiac, a podcast dedicated to raising the standard of education, awareness, and research on celiac disease and related autoimmune conditions. We have some exciting changes for this season. The Boston Children’s Hospital Celiac program has teamed up with the Celiac Disease Foundation to expand the reach of our educational podcast. Our goal is simple. To provide education to as many health providers and patient families as possible. I’m Vanessa Weisbrod and I’ve started a new role as the Chief Education and Community Engagement Officer at the Celiac Disease Foundation. In every episode, you’ll also hear from Janis Arnold, an incredible social worker at Boston Children’s Hospital, who is the voice of our patient stories.

Each month on the podcast, we will invite leading experts to dive into a hot topic related to celiac disease and look at how it impacts a patient family, the latest research and offer suggestions for health providers to manage these complex cases. Every episode of the Raising Celiac podcast is accredited by the Boston Children’s Hospital Continuing Education Department for physicians, nurses, social workers, dieticians, and psychologists. To claim your credits for listening to today’s episode, please visit dme.childrenshospital.org/raisingceliac. We’ll also drop that link into the show notes.

Thank you to the Global Autoimmune Institute and the Celiac Disease Foundation for making this podcast possible. Now, let’s get started with this month’s Raising Celiac patient story.

Janis Arnold:

Emily was diagnosed with type 1 diabetes at the age of eight. Her family quickly adapted to managing her condition, learning the ins and outs of blood sugar checks, insulin shots, and meal planning. At every appointment, Emily’s doctors reminded her parents that children with type 1 diabetes are more likely to develop other autoimmune conditions, particularly celiac disease. Still, Emily showed no obvious signs of digestive issues, so the possibility of celiac disease was far from their minds.

Vanessa Weisbrod:

Screening for other autoimmune diseases in children with type 1 diabetes is crucial because these conditions often co-occur, increasing the risk for complications. Early detection of diseases like celiac disease and thyroid disease allows for timely interventions which can improve long-term health outcomes and quality of life. Managing multiple autoimmune conditions can be challenging, but regular screening helps ensure that symptoms are caught and treated before they become severe. Additionally, proactive screening reduces the likelihood of misdiagnosis, which is vital for effective disease management in this vulnerable population.

Janis Arnold:

As time passed, subtle changes began to surface. Emily often felt more tired than usual, complained of occasional stomach aches and seemed bloated after meals. She also had frequent headaches. Her parents thought these symptoms might be connected to her diabetes management or simply growing pains. But as Emily’s energy levels dropped and the symptoms persisted, they decided to bring it up with her doctor.

Vanessa Weisbrod:

The most common symptoms of celiac disease include gastrointestinal issues like diarrhea, bloating, and abdominal pain, which can lead to weight loss and malnutrition. However, celiac disease can also manifest with lesser known symptoms such as fatigue, joint pain, and skin rashes. In some cases, individuals may experience neurological symptoms including headaches, brain fog and mood changes. Because symptoms can vary widely and may not always involve the digestive system, it’s important for individuals at higher risk of developing celiac disease to be regularly screened.

Janis Arnold:

During a routine checkup, her doctor ran some additional tests including a celiac disease screening since children with type 1 diabetes are at higher risk. The results revealed elevated tTG-IgA levels, suggesting that Emily might have celiac disease. Although she wasn’t showing severe symptoms, her doctor recommended further testing to confirm the diagnosis. Emily received an endomysial antibody or EMA test, which came back positive. With these results, her doctors explained that a biopsy of her small intestine was necessary to confirm whether the gluten was damaging her intestines.

The idea of Emily going through a biopsy was daunting for her family, but they wanted to be sure before making any major dietary changes. Living with diabetes was hard enough. The biopsy results were clear. Emily had celiac disease. The damage to her intestines explained her fatigue, stomach aches and bloating. Though it was overwhelming to learn she had to manage not just one but two lifelong autoimmune conditions, Emily’s parents were relieved to finally have answers.

Vanessa Weisbrod:

Current guidelines recommend that children with type 1 diabetes be screened for celiac disease at the time of diagnosis, and again, between two years and five years regardless of symptoms. This screening typically involves blood tests to measure levels of tissue transglutaminase antibodies, and in some cases endometrial antibodies. If the initial screening tests indicate elevated antibody levels, further evaluation including a biopsy is recommended to confirm the diagnosis of celiac disease. But what if there were a way to use the blood test to predict development of celiac disease in children with type 1 diabetes?

Could this help prevent complications and improve management of the diabetes? Could it reduce the need for a biopsy? We’ll discuss this and more on today’s episode of Raising Celiac. Today we talk about the possibility of predicting development of celiac disease in patients with type 1 diabetes with Dr. Dani Mallon from Cincinnati Children’s Hospital, whose research aims to improve screening methods for celiac in pediatric patients with type 1 diabetes. Dr. Mallon is also one of my favorite celiac doctors, and I’m so excited he’s agreed to join us today. Welcome Dr. Mallon to Raising Celiac.

Dr. Mallon:

Thank you very much for having me. This is a huge honor.

Vanessa Weisbrod:

And well, we are honored that you are here. So to get started, can you tell us what prompted you and your team to investigate better predictors for celiac disease in children with type 1 diabetes?

Dr. Mallon:

Yes, I would love to. I actually want to go back a little bit farther because the impetus for this research takes me back to my first real steps into the world of celiac disease as a clinician and a researcher. When I first arrived at Cincinnati Children’s, one of the earliest opportunities I had was the endocrinologists had reached out to our division, seeking some help with helping to manage the patients who had both celiac disease and type 1 diabetes. Because what they noticed was just like in a broader population of patients with celiac disease, many of the patients didn’t continue to follow up with GI, but of course, they continued to follow up with their endocrinologist for their diabetes management.

And the endocrinologists often didn’t quite know how to counsel them about their celiac disease, but they had a lot of questions, and so they wanted a partner in GI. The other question they had was, how do we implement this? At the time, back in 2014-2015, relatively nebulous landscape of a general recommendation to screen for celiac disease amongst patients with type 1 diabetes and with an interest in quality improvement, we set about trying to standardize a process for our screening. And that began a journey for me where I started to receive most if not all of the referrals for patients with type 1 diabetes and suspected celiac disease. We started to get these labs back and it wasn’t as black and white as the recommendations might indicate that they could be.

And so what we noticed was that there were plenty of patients with high tTGs, but whose biopsies came back normal when we took them for an endoscopy. And then there were plenty of patients who had very mildly elevated tTGs, but then when we took them to biopsy, they had full-blown celiac disease. So it started me asking questions about how can we try to identify the right patients to avoid unnecessary endoscopies? And also is there anything that we can learn about these patients before taking them to endoscopy that really gets us thinking that they truly have celiac disease?

Vanessa Weisbrod:

That’s so interesting, and I love that your experience really led you to ask these questions. It’s such a great way to start research. So how might early detection of celiac disease in these kids with type 1 diabetes help prevent complications associated with both autoimmune conditions?

Dr. Mallon:

So we know that patients with celiac disease are at risk for multiple health complications related to their celiac disease, including nutrient deficiencies like iron deficiency, osteopenia, poor growth, and then especially in patients with type 1 diabetes who already have a risk of cardiovascular disease from their diabetes. It seems like having a dual diagnosis may confer even more risk of cardiovascular complications. And so because many of these complications take time to develop, we take the stance that identifying and treating celiac disease as early as possible can help try to prevent those complications.

I think we do have definitely good studies that show that identifying celiac disease and treating it can improve weight, it can improve iron status and anemia. There are mixed results on whether or not it improves blood sugar control. There’s some studies that suggest that it doesn’t make a big difference, but there’s definitely some studies that it helps with blood glucose variability, trying to avoid very high or very low blood glucoses. And then we have mixed results on whether it has a meaningful impact on their quality of life because there are some studies that suggest there may be a reduction in their quality of life. Others say their quality of life is the same as other patients with type 1 diabetes.

Then there’s some studies that do suggest that there is an improvement in quality of life. And one of the most compelling sets of studies is when patients are identified as having celiac disease and they have good adherence to their gluten-free diet, they do have better outcomes both from a glucose control perspective as well as quality of life. So if we can put a team around them to help support them to achieve that great adherence to a gluten-free diet and great blood glucose control, then these guys can have a really excellent quality of life despite having two chronic diseases.

Vanessa Weisbrod:

And that’s what we all want, right? It’s so hard to have two conditions. It’s hard to have one condition, but getting to that place where you can manage it and have the best possible quality of life is just absolutely the most important thing. So your study identified elevated tTG-IgA levels greater than 10 times the upper limit of normal as a strong predictor of celiac disease. This may be an obvious answer to many in the celiac community, but for those listeners who are unaware of the ESPGHAN criteria, could you tell them about it?

Dr. Mallon:

Sure. We did set a cutoff of that 10 times the upper limit of normal because that’s what’s used in the ESPGHAN criteria and ESPGHAN is the European Society for Pediatric Gastroenterology Hepatology Nutrition. They’re our colleagues over in Europe and they proposed back in 2012 some criteria for diagnosing celiac disease without a biopsy. And then they revised those recommendations in 2020 to include a tTG-IgA level that is greater than 10 times the upper living of normal for that lab, and then also a second blood draw that identifies a positive endomysial antibody.

And that was also part of what we analyzed. And so we wanted to look specifically at whether or not the ESPGHAN criteria perform very well, specifically in a type 1 diabetes pediatric population.

Vanessa Weisbrod:

So how does the presence of positive EMA results complement the tTG-IgA levels in predicting celiac disease? Are both necessary for the strong prediction?

Dr. Mallon:

So our study did provide more data that helps support that there is a high positive predictive value that is a statistically important way of trying to identify how well a test performs at trying to predict true presence of disease. And so it does give a high positive predictive value when you have a positive EMA, but it’s not the whole story. And that was really what some of our early observations showed us is that we did have some patients with positive EMAs that didn’t have celiac disease when we took them for biopsy. So what we noticed is that having both a very high tTG greater than 10 times the upper limit of normal and a positive EMA, the vast majority of those patients do have celiac disease, but not all.

And that’s important. So it’s not always perfectly accurate in that there were two of our patients who had exactly those findings who had non-diagnostic biopsies. Even when we looked very closely at the biopsies again, we wanted to find out if this was just a misdiagnosis, but really we agreed again that this wasn’t true celiac disease at the time. And each of those patients have had a couple of years worth of follow-up and have still not been diagnosed. So it raises the issue that those criteria even put together are not perfect, and that’s important because if you put somebody on a gluten-free diet essentially for life, then that’s a really big deal.

Of course, we all agree. And we wanted to know if there are times when we have patients who don’t quite meet those criteria for celiac disease, but who do have abnormal labs to that extent.

Vanessa Weisbrod:

Absolutely. So one of the challenges that you mentioned in the study is that tTG-IgA can sometimes be falsely elevated in children with type 1 diabetes. How does your study address the issue of false positives and what improvements might it bring to reducing the unnecessary biopsies?

Dr. Mallon:

So what we’re proud of is that it was a large cohort of patients with type 1 diabetes, not just a mixed bag of other patients at high risk based on a family history or other autoimmune diseases, but specifically in type 1 diabetes. That we put forward a large group of patients. And our study mirrors a lot of the other studies that suggest that there are patients who have false positives. You’re going to have a higher rate of false positives if you have a mildly elevated tTG. And if you have a very elevated tTG, and especially because our assay allows us to detect way above the 10 times the upper limit of normal. The higher it gets, the more addictive it is that you truly have celiac disease.

And so mildly elevated tTG levels definitely are something where it’s not a done deal that you have celiac disease. And for patients who are thriving, it is appropriate to watch that patient, especially if the testing is done early in the diagnosis or at the diagnosis of type 1 diabetes. So we built into our screening algorithm to allow time to pass to see if those levels, especially mild levels, under five times the upper limit of normal to see if they get better over time. And I think that our study still supports that practice that a lot of celiac experts take on.

It also does help support the use of endomysial antibody as a secondary test that if it’s positive, it does increase your positive predictive value even at lower levels of tTG elevation. We also have this wide spectrum. And so if you have patients who have a persistently positive tTG or a rising tTG, and especially if they have a positive EMA, then it does seem like those are prime candidates to take for biopsy.

Vanessa Weisbrod:

Absolutely. So based on your findings, how might screening guidelines change for children with type 1 diabetes to improve this early detection of celiac disease?

Dr. Mallon:

This is a difficult question to answer because trying to come up with great recommendations that find all the patients that have celiac disease and don’t put too many kids under unnecessary procedures has been elusive because of the wide spectrum of what we find when we check these labs. And also our study lent more data to suggest that we can’t trust symptoms, and we only had some small signals over some other labs like ferritin might be a little bit lower in patients who truly have celiac disease, but it’s subtle.

And so what I do see for the future is that we should try to standardize an approach to screening, building an allowance for some abnormal labs and observation for mildly elevated levels, but also making sure that we take a patient to biopsy sooner if they’re showing signs of celiac disease, especially serious complications like poor growth. I think it does bear consideration and I think including endomysial antibody as a consideration for patients who have a screening positive tTG-IgA may help sway the decision about whether or not to take a patient for a endoscopy and biopsy. And we absolutely would endorse being cautious when assigning a lifelong diagnosis of celiac disease based on serologies alone.

Vanessa Weisbrod:

Absolutely. You don’t want to have to stick to that gluten-free diet if you don’t absolutely have to. So you mentioned that symptoms are not reliable predictors of celiac disease in this type 1 diabetes patient population. Can you talk a little bit more on why symptoms are less predictive in this group compared to the serological markers?

Dr. Mallon:

It’s a great question. I think it highlights that our serologic markers are pretty good, and we’re lucky to have such relatively accurate biomarkers, especially when they’re very high. But our population of patients with type 1 diabetes who are getting screened is definitely biased by selecting patients that are already at high risk of celiac disease because of their diabetes. So we’re going to have a disproportionate number of patients who have celiac disease but no symptoms because otherwise we wouldn’t necessarily be checking. There’s also a bit of, I think, some bias included when you have an abnormal lab and you go see a gastroenterologist to be evaluated for possible endoscopy.

You really dig in on those questions. Have you ever had any abdominal pain? Really even a little bit? And so I think we dig in and I think there also may be the power of suggestion. When you have an abnormal test, you start to second guess whether or not you’ve been paying close attention to any symptoms that may be subtle. And so I think it makes for a mixed population of patients who are asymptomatic with a high risk of the condition plus patients who may be labeled symptomatic, but in fact, the symptoms are relatively mild. And we already know that intermittent abdominal pain can be present in more than half of all school children, whether they have a disease like type 1 diabetes or celiac disease or none of the above.

And so because abdominal pain is common and because we’re asking such detailed questions and we have this patient population that’s already at high risk where you’re going to find some patients who are asymptomatic, I think that probably accounts for the wide spectrum of symptoms and no symptoms at all when it comes to celiac disease.

Vanessa Weisbrod:

What about the symptoms that are less classic or noticeable? I spent a lot of time working with families and kids going to school, and I’m always shocked by the parents who say, “Does it really matter if they have gluten at school? My child was completely asymptomatic.” And I say, “Well, what were their symptoms?” And they’ll say, “Well, they were diagnosed because they had really severe anemia or they weren’t growing quickly enough.”

And I always think to myself, “Well, aren’t those symptoms?” Because obviously it was not being on the gluten-free diet was causing them to be severely iron deficient or to not grow at the appropriate rate that they should be for a child. Is there any difference between the more physically noticeable symptoms and the more subtle ones?

Dr. Mallon:

When we get down to word choice, some people will call them symptoms versus signs, but in the end of the day, they’re all really meaningful and important impacts of the presence of celiac disease. And so I definitely take anemia and poor growth or poor weight gain as a very important symptom or sign because you’re already showing the signs of complications of celiac disease, not even just the presence of inflammation and damage in the intestine, but you’re seeing the downstream effects of it already. And we know that a lot of those take time to develop, and so we know that the problems have been there for a little while and are already showing themselves.

So I find that those sorts of non-immediate non-gastrointestinal symptoms, while they may be subtle and not immediately identified as celiac disease signs, they’re very important because they’re already down the road suffering the complications of celiac disease. I think those are really meaningful things because we can point to them and families can notice them, and they use those as motivation to stick to the diet even when they don’t have stomach aches or nausea or throwing up or diarrhea when they become exposed to gluten either knowingly or by accident. And I joke with my patients, I think it’s fortunate sometimes when patients have symptoms immediately when they have gluten because then they have this immediate feedback about whether or not they had gluten.

But I don’t love that it creates a fair amount of anxiety that they really don’t want to eat anything that has gluten because they’re afraid that they’re going to hurt. It’s definitely a double-edged sword about whether or not you have symptoms because it’s a tough sell for an asymptomatic patient who hasn’t developed any complications, but they know they have this other disease in celiac disease and maybe in our teenagers and more developed kids will know that it’s bad for them and their parents know that it’s bad for them, but they may not really internalize what it means to have this problem because they’re not having symptoms.

And so it really is a decision rather than a reaction to having symptoms whether or not they’re going to adhere to the diet. So it is a big challenge for our patients who are asymptomatic to follow the diet.

Vanessa Weisbrod:

For sure. Can you talk to our listeners about the role of the shared genetic predisposition, the HLA-DQ2 and DQ8 in patients with both type 1 diabetes and celiac and how the genetic factors could possibly impact your approach to screening?

Dr. Mallon:

So we know that HLA-DQ2 and DQ8 are shared genetic profiles between type 1 diabetes and celiac disease. It’s always been my understanding that DQ8 is a little bit more prevalent in type 1 diabetes, but it also accounts for a fair amount of the risk in celiac disease. And so we know that that underpins lot of the overlap between the two disorders. There’s also some science that may link the two through other immune mechanisms in the gut, and that probably has to do with their susceptibility conferred by the HLA genotypes. I think when it comes to clinical practice, there is some argument to checking a HLA genotype to see if they do have the risk of HLA-DQ2 and DQ8 because it’s not a hundred percent of patients with type 1 diabetes that have DQ2 and DQ8.

I think it also bears to note that not all patients with celiac disease have an identifiable DQ2 and DQ8. It’s just the very, very vast majority. And so I think there could be a role for checking genetics maybe to try to lower the anxiety and lower the frequency of screening. But I think for any patient, no matter what their genetic profile, if you do have an autoimmune condition that will put you at risk for celiac disease and/or if you have other signs or symptoms of celiac disease, it always bears evaluating even if you have been identified as having no DQ2 or DQ8 in your genetic profile. So I think there may be some promise of checking it, but I am always looking out for the exceptions to the rule.

And so I think there probably is some promise to using genetic profiling to try to stratify risk and guide screening over a child’s lifetime.

Vanessa Weisbrod:

Absolutely. So what are the clinical implications of your study for pediatricians managing children who have both celiac and type 1? How should they approach monitoring and diagnosing these patients?

Dr. Mallon:

Pediatricians, of course, serve indispensable function in managing their patients who have chronic diseases. There’s definitely pediatricians who shoulder a lot of the management for celiac disease and type 1 diabetes, especially if their specialists, endocrinologists and gastroenterologists, are not close by in proximity or if they have any difficulty in accessing them. I think it’s very important that pediatricians should know that screening is indicated and that it should be happening at regular intervals. I think it’s my experience that endocrinologists do a very good job of carrying out the screening in their patients, their type 1 diabetes, but pediatricians ought to know that it’s happening and/or filling in the gap if they’re not getting screened otherwise.

I think it’s also very important that the results that come back on celiac screening are not always black and white and that all patients should have their diagnosis of celiac disease made by a pediatric gastroenterologist who can sift through the nuances of serologic data. I think it’s also crucial to make sure that everybody taking care of these patients know that they should continue to eat gluten until a confirmatory test has been done and a consultation with a pediatric gastroenterologist has been done to make sure that any secondary testing or confirmatory testing is reliable because they’re still having gluten in their diet.

Vanessa Weisbrod:

Absolutely. And that’s one of the things, it’s always hard, right? That you have to make sure they’re still eating gluten, that they get the right test done and they get to the gastroenterologist because it’s not just getting to the gastroenterologist for the diagnosis, but all of the support that comes with actually getting that celiac disease diagnosis.

Dr. Mallon:

Right. And too often we have the experience of patients who have changed their diet or never really made it to the gastroenterologist, and were diagnosed with celiac disease based on labs alone, which our study and others have suggested that unless it’s very compelling, it may not be sufficient or accurate.

Vanessa Weisbrod:

So we’ve spent most of today talking about patients being diagnosed with type 1 diabetes first and then screening for celiac. Does it ever happen the other way around where a patient with celiac disease is then later diagnosed with type 1 diabetes?

Dr. Mallon:

Yes, it does. It is not common, but it does happen. And in some studies it’s estimated between five and 7% of patients with both celiac disease and type 1 diabetes were diagnosed with their celiac disease first. It has been a gratifying experience when I’ve helped make the diagnosis in my patient with celiac disease where you’re checking for signs of type 1 diabetes and they actually had it. And so getting them keyed in to the diagnosis of their type 1 diabetes felt like a real win for that patient where we knew what we were looking for in follow-up in their celiac disease. I think the other new things on the horizon, really they’re here, is screening for patients with celiac disease for the possibility that they have type 1 diabetes in early stages that are pre-symptomatic.

And so there’s this idea that there are patients with the antibodies that cause the damage in type 1 diabetes that lead to the pancreatic dysfunction where you don’t make insulin anymore. But that early stage where they just have antibodies but no symptoms and normal blood glucose is you can identify those patients through antibody screening. And then the data on preventing diabetic ketoacidosis, which is a very dangerous outcome of uncontrolled diabetes that oftentimes is present when patients first get diagnosed with diabetes. If you can prevent that condition as their first manifestation of their diabetes, then that is a really big win to prevent a life-threatening condition.

And then there’s also some new medications out that may have the promise of delaying the onset of type 1 diabetes. So it’s something that a lot of us in the celiac world are starting to do is to encourage our patients to be screened for type 1 diabetes through antibody testing.

Vanessa Weisbrod:

That’s so great. So how do the findings in your study impact the way healthcare providers should advise patients with both conditions on dietary management and long-term monitoring?

Dr. Mallon:

So I mentioned this earlier, but there have been a couple of great research studies that indicate that adhering to a gluten-free diet and being successful in the diligent management of diabetes leads to a better quality of life and better short and long-term health outcomes. Anecdotally, and also in those research studies, patients are often doing excellent at both and really thriving, but often are struggling with both too.

And so there’s so many factors that go into managing both diseases, that I’m a big advocate for a multidisciplinary team to handle both their type 1 diabetes and their celiac disease with a great gastroenterology team and a great endocrinology team, and it’s even better when those teams are working together.

Vanessa Weisbrod:

Absolutely. So important. So what are the next steps in research to refine these serological thresholds for celiac diagnosis in the type 1 diabetes population? Are there other markers or tests you believe could further improve the diagnostic accuracy?

Dr. Mallon:

Yes. So I think through this study and through reading other researchers’ excellent work, that the combination of endomysial antibody as a secondary blood test in addition to the tTG-IgA screening antibody, that combo is a really important way to try to identify patients with celiac disease. One thing that we’ve found in our study is that if you’re a little bit more exacting in the way that you do your endomysial antibody testing by finding the most dilute sample of blood that’s still positive.

It’s essentially getting a degree of positivity of the endomysial antibody can really help zero in on patients, much like the degree of elevation of tTG-IgA. I think there’s also some new advances in the field around genetic screening as well as new biomarkers like IL-2 and microRNA profiles, and then metabolomic data that’s still coming out. It seems like it’s relatively new on the block and not ready for clinical prime time use, but I think there’s real promise in some of these newer biomarkers for true celiac disease that may be incorporated into new screening approaches.

Vanessa Weisbrod:

Wow. Well, Dr. Mallon, this has been such an amazing discussion and we are all truly so grateful for all of the incredible work that you’re doing. So now before we end for the day, let’s find out where our patient Emily is today.

Janis Arnold:

Adjusting to a gluten-free diet while managing her diabetes wasn’t easy, but with the support of her healthcare team, Emily slowly regained her energy. Today, her family is grateful for the early detection, even though Emily’s symptoms were subtle. In her own words, Emily says, “Having celiac and diabetes is really hard, but I’m learning how to still be involved in fun things like birthday parties and hanging out with friends. I know that I’m going to grow up to be strong and healthy because my doctor found out I had both diseases really fast.”

Vanessa Weisbrod:

And now a word from the Global Autoimmune Institute.

Speaker 4:

The Global Autoimmune Institute works to empower solutions in the diagnosis and treatment of autoimmune diseases through research, education, and awareness while supporting multidisciplinary approaches to health. We are thrilled to support the production of this educational podcast.

Vanessa Weisbrod:

Thank you for listening to this episode of Raising Celiac. A special thanks to the generous contributions from the Global Autoimmune Institute to make this podcast possible. A reminder to all physicians, nurses, social workers, dieticians, and psychologists to claim your continuing education credits for listening to today’s episode, please visit dme.childrenshospital.org/raisingceliac. If you like what you heard, be sure to write a review, like and subscribe wherever you get your podcasts. For more information, check us out on social at Boston Children’s Celiac on TikTok, at Children’s Celiac on Twitter, or at Celiac Kids Connection on Instagram. Have a great month.