Season 2 Episode 4: Potential to Use IL-2 for Celiac Diagnosis 

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.