By Amy Ratner, director of scientific affairs

Update: In October 2023, this study was published in the American Journal of Gastroenterology as a research letter. You can read it here.

A higher income, living in an urban area and living close to a celiac disease center are all positively correlated with celiac disease prevalence, while being Black or Latino/Hispanic is negatively correlated, according to a poster presented at Digestive Disease Week (DDW) by Columbia University and Beyond Celiac.

“These results suggest that disparities in healthcare access may contribute to the underdiagnosis of celiac disease, particularly among the non-white population in the United States,” the analysis of data compiled by Beyond Celiac and the National Minority Quality Forum (NMQF) found.

Analyzing the Data

The poster, presented by Haley Zylberberg, MD, a gastroenterology fellow at Columbia University who analyzed the NMQF data, was based on 2016 Medicare claims data at the three-digit zip code level. The analysis divided sociodemographic variables – median income, race, urban areas and proximity to a celiac disease center into four equal groups, or quartiles. Likewise, the percentage of celiac disease relative prevalence was divided into four increasing groups, ranging from .02 percent to .95 percent.

The results showed that as the median income increased quartile by quartile, so did the prevalence of celiac disease.

Meanwhile, the percent of Latino/Hispanics with Medicare claims for celiac disease decreased the as percentage of relative celiac disease increased. For Black people, this was also largely true. The data analysis was designed to evaluate the associations between celiac disease and sociodemographic variables at the zip code level.

Our Ongoing Support of CD Research

The poster is one of two with ties to Beyond Celiac being presented at DDW. The other, based on a qualitative study of responses from adults who participated in surveys in the Go Beyond Celiac patient registry, details how frustration and distress about symptoms lead most people with celiac disease to seek a diagnosis. It was presented by Erin Miller, MPH, Beyond Celiac associate science project manager.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. NMQF is a national research and educational organization dedicated to ensuring that high-risk racial and ethnic populations and communities receive optimal health care.

This is the second year that data analysis based on the Beyond Celiac/NMQF project has been presented at DDW. In 2022, preliminary analysis and mapping of claims showed someone’s race and ethnicity and what part of the United States they live in can affect whether they are diagnosed with celiac disease. More than 70,000 Medicare beneficiaries had at least one celiac-disease-related claim in 2016.

These beneficiaries were located primarily in the Northeast and Midwest. Meanwhile potentially undiagnosed celiac disease, based on beneficiaries with combined claims for irritable bowel syndrome (IBS) and anemia, showed the opposite geographic distribution, with beneficiaries primarily located in the South and East. Nearly 11,000 Medicare beneficiaries had these combined claims.

The post Healthcare disparities may contribute to underdiagnosis of celiac disease appeared first on Beyond Celiac.

Kate Avery, Director of Research & Patient Engagement

A clinical trial testing a new celiac disease treatment has launched in the United States. Chugai Pharmaceuticals is testing their potential celiac disease treatment DONQ52 in a Phase 1 clinical trial. Phase 1 trials test the safety of a drug and how well study participants tolerate different dosages. Phase 1 clinical trials are the first step in the human clinical trial process that all drug candidates must go through before they are approved by the FDA and available to patients.

When people with celiac disease ingest gluten, the immune system reacts as if the gluten is a foreign invader. DONQ52 is a monoclonal antibody that is designed to inhibit this reaction of the immune system to gluten, stopping the process that causes the damage of celiac disease. A preclinical study presented at Digestive Disease Week in May 2023, showed that DONQ52 may be effective in blocking gluten-specific immune reactions. Blocking the immune system’s response is one of several current approaches in the drug development pipeline to finding a treatment beyond the gluten-free diet. You can learn more about the immune system’s gut reaction in celiac disease in this video.

This trial, called the LILY Study, is split into two parts. Qualified participants will only complete one part of the study. In Part A, participants are given 1 dose of DONQ52 or a placebo (via injection) during a 3-night stay at a clinical site and are monitored for any potential side effects or issues. They also complete daily symptom questionnaires at home for 8 weeks, using a mobile app. For participants in Part B, all visits are outpatient, and participants are given 7 doses of DONQ52 or a placebo (via injection) at a clinical site over 10 weeks and complete daily symptom questionnaires at home on the mobile app for 16 weeks. There is an option for follow-up visits in both parts of the study to take place at the participant’s home by a mobile nurse, rather than having to travel to a clinical site. Neither part of the trial involves a gluten challenge or any intentional gluten consumption.

To qualify, participants must be 18-70 years old and following the gluten-free diet for at least 12 months. Other qualifications also apply. Participants will be required to maintain a gluten free diet throughout the study and provide medical records to confirm their celiac disease diagnosis.

Compensation will be provided to those who participate and reimbursement for travel costs is also available. If you are interested in participating, but do not live close to a study site, the study encourages you to still complete the screening survey to see if you qualify. More information about travel reimbursement and at-home options will be provided to potential participants who qualify.

To find out more about the study and see if you qualify, visit this link. Beyond Celiac is helping to recruit for this study as part of our commitment to accelerating research.

The post LILY Study launches to test monoclonal antibody treatment for celiac disease  appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

In children with celiac disease, it can be a challenge to connect the dots between any gluten getting into the child’s diet and the consequences, especially if the child does not have any symptoms.

In a recent study, Boston researchers set out to determine if tests that measure gluten in urine and stool can be used as markers of gluten exposure in children on the gluten-free diet.

The study found that children with celiac disease who had detectable amounts of gluten in their urine and stool did not have any symptoms. However, overall, the number of children with detectable immunogenic protein (GIP) in urine and stool samples was small, the study says. GIPs are fragments of gluten proteins that are resistant to digestion by enzymes in the gastrointestinal tract.

The study supports previous research that shows symptoms are not a reliable way to determine if a child has been exposed to gluten, the authors note. A 2016 study found that one in five children with celiac disease may not heal despite following the gluten-free diet for at least a year, with neither positive results of celiac disease blood tests nor symptoms being reliable predictors of intestinal damage.

Meanwhile, none of the children in the new study who had persistent damage to the intestine had detectable levels of gluten in urine samples taken at the time they had endoscopies done.

Testing in three settings

In the multicenter collaboration by Massachusetts General Hospital and Boston Children’s Hospital, scientists tested at least one urine sample from 84 children and at least one stool sample from 22.  Study participants ranged from six to 21 years, and all had been on the gluten-free diet for at least 6 months. Seventy percent of study participants reported that they had no symptoms. Most study participants provided a single sample.

The samples were collected in three settings: a facility where children were having an endoscopy, a gastroenterology clinic and in the study participants’ homes. This is the first time testing children at home was evaluated. The researchers wanted to investigate the tests in real world settings, they note.

The authors concluded that more research is needed to understand the range of gluten excretion in children and how specific and sensitive testing is before the tests can be used to give rapid results in a doctor’s office, clinic or other medical care setting.

Number of samples with GIP

Currently, how well a child is following the gluten-free diet is determined by a dietitian’s evaluation of the child’s diet, questionnaires, blood tests for antibodies to gluten and symptoms. Study authors called this method “highly subjective and notoriously inaccurate.” They set out to determine if tests for GIP in urine and stool could provide an objective and non-invasive way to determine if gluten is getting into a child’s diet.

Detectable GIP was found in about 9 percent of 44 stool samples and about 5 percent of 125 urine samples.

These rates were low compared to earlier adult and pediatric studies conducted in Europe, which reported a 13 percent to 24 percent rate of GIP in stool and a 5 percent to 38 percent in urine. All the children who participated in the Boston study came through specialized celiac centers where 93 percent were counseled on the gluten-free diet. This dietary education might have improved adherence to the gluten-free diet, the study says.

Although repeat sampling is more likely to detect gluten, the study was designed to evaluate how practical it would be to screen for gluten in a doctor’s office or other medical setting where a single sample collection is preferable. The study authors acknowledged that the timing of GIP excretion after gluten is consumed is also a potential detection limitation. The window for detecting gluten in stool is longer than urine, 24 to 72 hours compared to 3 to 6 hours, the study says.

Children with persistent damage

For children in the study who had persistent intestinal damage revealed through a biopsy but no evidence of GIP in urine, the authors suggest these study participants may have been ingesting enough gluten to trigger inflammation but an amount that was below the level of detection of the urine test.

The amount of gluten needed to trigger intestinal damage is not well-defined and is known to vary, the authors note. 

Alternatively, subjects might have changed their diet in the short-term, avoiding gluten in the days leading up to the endoscopy even though they did not know that testing for gluten in urine was going to be done. Long-term gluten exposure might have been the trigger for the persistent intestinal damage found in biopsies, the study says.

Other research has found that nearly 100 percent of study participants who had intestinal damage had GIP in urine samples. 

Future direction

Testing of multiple urine samples for GIP could potentially make the tests more useful when used to detect gluten exposure in those who have persistent intestinal damage found through an endoscopy and biopsy, the study says.

Study limitations include the small number of samples and the limited number of multiple samples from all study participants. The authors note that it was more difficult for study participants to collect samples in some settings than others, which will be useful to know for future research. Future research will also benefit from general sampling recommendations since there is variation in the dynamics of gluten absorption and excretion, the study says.

This “will help clarify the interpretation of positive and negative GIP results across all collection settings,” the study concludes.

Glutenostics, the company that sells the urine and stool tests in the United States, sponsored the study.

You can read more about the study here.

The post In kids with celiac disease with no symptoms, tests still find evidence of gluten in their diets appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

Increasingly, numerical scores measure how we’re doing in everything from the Wordle word game to how many steps we take every day to how many minutes we spend on social media.

Now, a group of international researchers has come up with a five-point scoring system for those with celiac disease to determine the risk of having persistent intestinal damage.

The score is based on how old you were at diagnosis, the kind of symptoms you had when diagnosed, how well you have responded to the gluten-free diet and how well you keep to the gluten-free diet.

Those diagnosed at 45 years of age or older who had classic symptoms at diagnosis, have had a poor response to the gluten-free diet and/or don’t adequately follow the gluten-free diet, would have the highest score, a five, and would be most likely to have persistent damage to the intestine.

Persistent intestinal damage linked to complications

This persistent intestinal damage predicts increased development of complications and mortality in adult patients, the study, published in the journal Gut, also found.

The scoring system, which is based on information from diagnosis and follow-up, could be used as a “personalized and cost-effective approach to determining the need for a follow-up biopsy,” according to study authors from institutions in the United States, the United Kingdom and Italy.

A number of researchers have been looking for a method of predicting whether someone’s intestine is healing on a gluten-free diet without resorting to an endoscopy and biopsy, which are invasive and carry some risks. But scientists have not yet discovered a biomarker, a kind of red flag raised by the body, that can be readily measured to indicate when there is damage in the intestine.

Until a biomarker is found, a biopsy is the only way intestinal damage or healing can be determined. While follow-up biopsy in all patients is not routine, guidelines suggest that the procedure be done when patients do not recover on a gluten-free diet.

Meanwhile, up to 40 percent of those with persistent intestinal damage due to celiac disease do not have ongoing symptoms, the study says.

“Our score allows clinicians to identify these patients are higher risk even in the absence of ongoing symptoms,” the authors wrote.

While some persistent intestinal damage is caused by serious complications related to celiac disease, in most cases it can be traced to how well someone is following the gluten-free diet, according to the study.

How the scoring is done

The scoring system works like miniature golf, where the higher the number means the worse you are doing.

Diagnosis at 45 years or older, classical presentation of celiac disease, and lack of response to the gluten-free diet all receive one point in the score tally. Poorly following the gluten-free diet receives two points. The score is calculated by adding these points. Classical celiac disease presents as diarrhea, weight loss and fatty stools. Examples of classic celiac disease include patients with diarrhea and weight loss or weight loss and anemia.

Someone with a score of one or less is unlikely to have persistent intestinal damage and would not need a follow-up biopsy, while those with a score of three to five would be considered high risk and a follow-up biopsy should be done. A score of two would indicate intermediate risk and should be evaluated on a case by case basis.

The study provides evidence that the risks of celiac disease are based on more than intestinal damage, but are also related to age and clinical presentation, for example, weight loss, said Dan Leffler, MD, a gastroenterologist at Beth Israel Deaconess Medical Center, medical director of clinical science at Takeda Pharmaceutical Company and a study author.

How the study was done

Study participants included 694 adult patients diagnosed at celiac centers at the University of Pavia, Italy, Royal Hallamshire Hospital, Sheffield, UK and Beth Israel Deaconess, Boston, from 2000 to 2020. All had follow-up biopsies. Of these, about 23 percent were found to have persistent intestinal damage. Among those with persistent damage, 21 percent had complications of celiac disease. Biopsy results and data about follow-up, including development of complications and mortality, were collected and reviewed.  

Clinical response to the gluten-free diet was defined as improvement or end to symptoms and abnormalities in celiac disease blood tests and nutritional deficiencies that had been found at diagnosis. Persistent intestinal damage, also called persistent villous atrophy, was defined as measuring above a certain level on follow-up biopsy despite a gluten-free diet. An interview with a dietitian and response to questionnaires about the diet were used to determine how well study participants were following the gluten-free diet.

Complications of celiac disease were defined as malignant and pre-malignant abdominal conditions, including refractory celiac disease type 1 and 2, ulcerative jejuno-ileitis, abdominal lymphomas and small bowel carcinomas.

Nearly 84 percent of study participants were following the gluten-free diet. About 34 percent had ongoing symptoms.  

Persistent intestinal damage common

Persistent intestinal damage is “a common clinical scenario,” the study says.

Complication-free survival and overall survival were significantly lower in those with persistent intestinal damage compared to those who had intestinal recovery from the damage of celiac disease.

Results that show persistent intestinal damage is associated with increased complications and mortality “fill in an important gap in the natural history of celiac disease,” the study says. The findings complete a picture of the sequence of events in which persistent inflammation and tissue damage lead to poor long-term health. This also occurs in other chronic diseases, including inflammatory bowel disease, the study notes.

A second group of adult study participants with celiac disease who had follow-up biopsies mainly from 2020 to 2022 were enrolled and their results were used to test how well use of scores to predict risk of persistent damage worked. Results regarding persistent intestinal damage in this group were similar to those found in the first group, about 20 percent.

Ongoing damage related to poor adherence to gluten-free diet

Overall, about 80 percent of ongoing damage was attributed to poorly following the gluten-free diet, while 20 percent was due to malignant complications, the study found.

About half of the cases of complications were due to refractory celiac disease type 1, which the study says has “the best prognosis among the complications of celiac disease.” This type of refractory celiac disease is marked by a lack of response to a strict gluten-free diet after six to 12 months, with symptoms, intestinal damage and an abnormal population of white blood cells in the gut. Type 1 is the less severe form of the condition. The authors also note that refractory type 1 may be related to gluten being consumed unintentionally.

Poor gluten-free diet adherence was the most significant predictor of intestinal damage in all study analyses, the authors wrote. “This is not surprising and confirms that poor gluten-free diet adherence is a risk for poor outcomes in celiac disease,” the study says. “This underlines the importance of strictly following a gluten-free diet for patients with celiac disease.”

While the scoring system would lead to more frequent biopsies in those whose tally is high, Leffler said it is reasonable to follow older patients more frequently. “This is not different from what is done for a lot of inflammatory gastrointestinal diseases, such as ulcerative colitis where dysplasia screening is more frequent with age,” he added.

As for what patients who have biopsies that reveal intestinal damage despite following a gluten-free diet should do, Leffler said it’s a good question. In the absence of treatments outside the gluten-free diet, it’s “really an individualized discussion between the patient and their clinical team,” he said.

You can read more about the study here.

The post Running the numbers in celiac disease appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

Results of research funded by Beyond Celiac point to a more precise way that gluten sets off damage to the intestine in those who have celiac disease and could help in the development of innovative approaches to finding a treatment.

The study, by Arnold Han, MD, a gastroenterologist at Columbia University and recipient of the Beyond Celiac/Society for the Study of Celiac Disease Early Career Investigator grant, describes the way gluten triggers two kinds of T-cells to coordinate and cause damage.

New clues

T-cells are white blood cells that function as the body’s disease fighting soldiers and are part of coordinated immune system battle. In the case of celiac disease, these soldiers incorrectly read gluten peptides as the enemy, rally the immune response troops and go on the attack, with resulting destruction of the absorbing lining of the intestine.

 The new study, published in the journal Science Immunology, provides important clues about the way CD4 T-cell responses to gluten ultimately lead to intestinal damage by intraepithelial lymphocytes. Intraepithelial lymphocytes are T-cells found in the intestinal tract.

“We show that gluten somehow induces rapid and deliberate activation of the [intraepithelial lymphocytes],” Han said.

This was somewhat unexpected because the intraepithelial lymphocytes are not thought to recognize gluten on their own, he noted. The study suggests that these cells shift from anti-inflammatory defenders to pro-inflammatory attackers, leading to intestinal damage.

Role in developing new approaches to treatment

Evidence from the study, which is ongoing, could be used in the development of new treatments for celiac disease based on what it reveals about the way that gluten causes the immune reaction in celiac disease.

“An improved understanding of any disease process can inform new avenues for therapy,” Han said. Many celiac disease drugs currently being developed focus on the activation of the CD4 T-cells, but this new research with its improved understanding of how the intraepithelial cells are activated could contribute to treatments that target them, he noted.

Han and colleagues at Columbia University analyzed T-cells from the intestinal biopsies of 37 study participants in three categories — 11 with who had just been diagnosed and were considered to have untreated celiac disease, 19 with active celiac disease on a gluten-free diet and seven with potential celiac disease who had positive blood tests for celiac disease antibodies by no damage to the intestine. The study also included 17 participants who did not have celiac disease.

How study was done

Study participants in all three categories of celiac disease had an enriched number of intestinal T-cells, including CD4 helper cells, regulatory T-cells and CD8 intraepithelial cells.

Blood samples from study participants who had been on a strict gluten-free diet for at least six months and volunteered to eat four slices of gluten-containing white bread per day for three days, a gluten challenge, were also analyzed.

In celiac disease, although intestinal damage can heal completely on a gluten-free diet, changes in the intraepithelial cell population can persist for years, Han said. These persistent cells have distinct T-cell receptors and researchers are working to understand what the receptors are recognizing if it is not gluten. The receptors on the surface of T-cells play a significant role in immune response by activating the cells to respond to antigens, acting as a kind of warning system alarm switch. An antigen is a marker that tells your immune system whether something in your body is harmful or not.

Investigating antigens

In celiac disease, gluten is the antigen recognized by CD4 T-cells. “However, we don’t know the antigens for these intraepithelial cells that appear to cause damage,” Han noted. Previous research done by Han suggested that microbial antigens, which are microorganisms including bacteria, viruses and more, or self-antigens, which are normal substances found in a person’s body, are potentially being recognized by the intraepithelial lymphocytes.

The new study found that groups of cells that shared the same T-cell receptors, called T-cell clones, which were present in the intestinal biopsies of study participants with celiac disease were later seen in the blood following the gluten challenge. Researchers were able to track how a given T-cell clone behaved and found that the T-cells in the intestine were changing to become more inflammatory in the blood, Han said.

In ongoing research Han and colleagues are aiming to better understand how intraepithelial cells are activated by gluten. His research will also include study of celiac disease using organoids, tiny three-dimensional mini organs grown in a petri dish from the intestinal cells of celiac disease patients.

You can read the study here.

The post New insights into the way gluten causes damage in celiac disease revealed in Beyond Celiac funded research appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

Even celiac disease patients who were following a gluten-free diet and felt well were still unintentionally consuming some amount of gluten that was detected in stool tests, according to preliminary results of a study recently presented as a poster at Digestive Disease Week (DDW).

Australian researchers had set out to determine how tests for gluten in stool can best be used as an objective tool to monitor the gluten-free diet both by physicians treating patients and in clinical trials. They were interested in determining the best time to test for gluten and the lowest amount of gluten that could reliably be detected in a stool test.

Their study was designed to evaluate tests for gluten in stool in a real world scenario that mimicked “accidental, low-dose gluten exposure.” It also aimed to compare stool testing to traditional ways of evaluating the adequacy of the gluten-free diet, such as blood tests for celiac disease antibodies. Fifty two study participants who had been on the gluten-free diet for at least one year were recruited for the study.

The study called for participants to eat a cookie containing one of several amounts of gluten, followed by measurement of gluten immunogenic peptides (GIP) found in all stool samples collected for one week.

But even before study participants were given the cookies, preliminary tests found that 87 percent had one or more stools samples containing gluten, which researchers called “high background gluten excretion.” This was despite the fact that preliminary blood tests for gluten antibodies, excellent gluten-free diet adherence test scores, and daily symptom monitoring indicated that gluten was not getting into the patients’ diets.  

Those findings prompted researchers from the Walter and Eliza Hall Institute and colleagues to follow-up their original study with a second investigation into background gluten exposure with 12 of the celiac disease patients from the first study.

Study one

For the first study, researchers included 29 participants who had no detectable gluten in stool samples taken immediately before the gluten challenge was initiated.

Participants were given 50, 250, 500 or 1000 milligrams (mg) of gluten or a placebo in a cookie. They then collected samples of all stool for one week.  Celiac disease blood tests were done at the beginning and end of the study and symptoms were monitored daily, Additionally, study participants completed a food diary and a behavior questionnaire that asked about lifestyle, knowledge of the gluten-free diet and diet practices.

GIP was detected in stool samples of all participants except those who got the placebo.

The amount of gluten in the cookie did not correlate with the amount of gluten in the stool, but higher amounts were detectable for a longer time. For example, gluten was detectable for up to six days following a 1000 mg challenge, but only for two days with a 50 mg challenge. Additionally, acute gastrointestinal symptoms increased significantly after the 1000 mg dose but did not occur consistently with less gluten.

Study results lead researchers to conclude that the optimal testing window after a suspected gluten exposure is one to two days.

Study two

In the follow-up study, researchers set out to determine the sources of gluten in the regular gluten-free diet of 12 original study participants and to test whether they were consistently being exposed to gluten over time. Researchers selected participants to cover a range of high to low gluten detection in the earlier, pre-study stool tests.

Study participants followed their regular gluten-free diet and collected stool samples three times a week for two weeks.  Test results showed that GIP detections “remained remarkably consistent” for each participant over time from the first study to the second.

If a person had gluten in all or most samples during the initial monitoring, they had the same levels in the follow up study one to two years later, according to the authors. Similarly, if someone was negative in the first study, they likely remained negative.

“This indicates gluten exposures are more than random occurrences and may reflect long-term lifestyle and dietary behaviors,” the authors note.

In addition to stool tests, study participants again reported on their diet and filled out the lifestyle questionnaire. The questionnaire revealed a trend in which people who rarely dined out or only dined out in gluten-free accredited restaurants tended to have lower levels of GIP in stool tests, the study says. However, matched food diaries reviewed by a dietitian “did not reveal any obvious sources of gluten exposure in participants with high GIP levels,” the authors wrote.

While dining practices are an important consideration, more data is needed to understand sources of unintended gluten exposure, the study concludes. The researchers are currently doing studies examining GIP detection in stool and gluten in food samples, particularly as these relate to celiac disease patients who have inexplicably high levels of gluten in stool samples despite seemingly being seemingly excellent in follow the gluten-free diet.

 A previous study in the United States and Canada compared gluten from samples of food to gluten in stools. When food tested positive for gluten peptides, it was associated with a positive stool test in 83 percent of cases.

Overall conclusions

Results of the two studies suggest that gluten excretion and therefore gluten consumption is common in people with celiac disease who are seemingly healthy. Ninety four percent of study participants self-reported high adherence to the gluten-free diet and all had negative blood tests for celiac disease antibodies.

If used to monitor a celiac disease patient’s gluten-free diet, more than one stool test would be needed, the study concludes.

However, the high sensitivity of tests for GIP in stool means some positive test results might not be significant in managing treatment for those with celiac disease. More study into the relationship between GIP in stool and intestinal damage is required to appropriately interpret a positive GIP result, the study says.

“A negative GIP result may be more informative than a positive result,” researchers concluded, noting that a negative result could be a way to rule out gluten exposure in celiac disease patients who continue to have symptoms on the gluten-free diet.

Additionally, since positive GIP might not be an indication of clinically significant gluten exposure, how to use stool tests in clinical trials has yet to be determined, according to the study. A positive GIP result alone might not be adequate reason to exclude a person from participating in a clinical trial, the authors note.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW as posters are often preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed journal. Posters selected to be presented at DDW go through a review process.

The post Stool tests reveal it’s common for unintended gluten to get into a strict gluten-free diet appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs.

Two separate studies related to race and potential healthcare disparities in celiac disease were presented recently as posters at Digestive Disease Week (DDW).

Researchers at the University of Alabama investigated the frequency with which the genes associated with celiac disease were found in Black people. 

And investigators at the Cleveland Clinic looked at differences in the frequency of blood testing for celiac disease in those who had a biopsy that showed intestinal damage. They were seeking to determine whether Black people were tested for celiac disease at the same rate as white people.

Genes for celiac disease

Black people are at genetic risk for celiac disease, the University of Alabama researchers concluded.

“Genetic risk and prevalence of celiac disease in Black people is largely unknown and thought to be rare,” the study says, leading researchers to launch their investigation.

Researchers reviewed records of adults who had haplotyping tests done at the University of Alabama HLA laboratory primarily to be considered as organ donors or recipients. The study included about 11, 500 Black people and about 14,000 white people.  The University of Alabama HLA lab, the only accredited HLA lab in the state, maintains a registry of all HLA typing performed, as well as patients’ demographics, the authors wrote. University of Alabama has a diverse patient referral base, the study notes. Haplotyping can identify patterns of genetic variation that are associated with health and disease.

DQ2 gene similarly frequent

Black people had similar frequency of having HLA DQ2 alleles, but less frequent HLA DQ8 alleles than whites, the study found. Alleles are one of two or more versions of a genetic sequence at a particular region on a chromosome. An individual inherits two alleles for each gene, one from each parent.

HLA DQ2 and HLA DQ8 are the genes found in almost everyone who has celiac disease, with only one copy of one of the genes needed to develop the condition. But genes alone are not enough. In fact, the genes associated with celiac disease are found in 30 to 40 percent of the general population, but only 1 percent of the general population has celiac disease.  Environmental factors are also involved in the development of celiac disease, though the exact cause has not yet been determined. Gluten from wheat, barley or rye also must be consumed for someone with the associated genes to develop celiac disease.

About 5,500 Black people and about 6,500 white people had the genes associated with celiac disease, the study found.

Among those with the genes, about 35 percent of Black people and 33 percent of white people had one copy of the DQ2 gene, while about 3 percent in each group had two copies of the DQ2 gene.

About 2 percent of Black people and 7 percent of white people had one copy of both DQ2 gene and DQ8 gene.

While these percentages reflect how common the genes were in both study groups, they may not reflect how common they are in the general population because study participants were all being evaluated to be transplant organ donors or recipients, said Amanda Cartee, MD, a gastroenterologist at the University of Alabama and one of the study authors. Cartee presented earlier data at DDW in 2022 that showed Black people are much less likely than white people to have gene tests for celiac disease.

DQ8 more frequent in white people

About 16 percent of white people in the new study had one copy of the DQ8 gene, compared to about 6 percent of Black people. Two copies of the DQ8 gene were found in 0.6 percent of white people and about 0.08 percent of Black people.

The study also found that about 50 percent of Black participants and about 40 percent of white participants had haplotypes other than DQ2 or DQ8 and would be highly unlikely to develop celiac disease. Cartee noted there is some emerging data on another gene that might be related to celiac disease, but that was not evaluated in this research.

Study limitations include the fact that the study population was largely composed of those undergoing transplant evaluation. Additionally, there are disparities in evaluation for transplants and transplantation, the authors note.

The study was limited to an investigation of who had the genes associated with celiac disease and was not designed to determine who went on to to develop celiac disease. Additional studies that assess the frequency of genes related to celiac disease in diverse populations and investigate the progression to celiac disease in those who have the genes are important to understanding the role of genetic risk in non-white populations, the study authors note.

Evidence of intestinal damage and celiac testing

Cleveland Clinic researchers reviewed 10 years of health records of adults who had biopsies that showed intestinal damage to determine if they had subsequent blood tests for celiac disease. Their study included about 1,700 patients. Of these, about 130 were Black.

“Recent work has shown an increased prevalence of celiac disease among numerous racial and ethnic groups, but diagnosis is affected by the frequency of testing.” the authors wrote. “We sought to assess health disparity in celiac disease.”

Overall, about 73 percent of white patients, about 1200, had celiac disease blood tests done, compared to about 55 percent of Black patients, about 70. A significant difference in testing frequency was found when researchers analyzed results based on race alone.

But when they considered other factors, including gender and age, being a man was the only factor significantly associated with having been tested for celiac disease less frequently. “The frequency of testing was lower among [Black] patients, but not after correcting for age and gender,” the study says.

Meanwhile, older study participants were tested more frequently.

Among white people who were tested for celiac disease, the test was positive in about 43 percent compared to about 15 percent in Black people.  Blood tests for celiac disease included anti-tissue transglutaminase (TTG) IgG or IgA, anti-endomysial (EMA), or anti-deamidated gliadin peptide (DGP) antibodies.  Researchers concluded that advocacy for increased testing in men and Black patients with intestinal damage is needed.

An earlier study, the one presented by Cartee in DDW in 2022, found that Black people with biopsy confirmed celiac disease were more likely than non-Hispanic whites to have had negative results on the TTG test, raising questions about its accuracy in diagnosing celiac disease in Black patients.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW as posters are often preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed journal. Posters selected to be presented at DDW go through a review process

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By Amy Ratner, director of scientific affairs

Women with celiac disease are at increased risk for pregnancy and delivery complications compared to women without celiac disease, according to study that looked at the hospital records about 12 million pregnant women.

Overall, women with diagnosed celiac disease were less likely than women who do not have the condition to have a full-term, uncomplicated delivery, the study presented recently at Digestive Disease Week found.

Additionally, babies born to pregnant women with celiac disease were also more likely to be small for gestational age and show distress during delivery, according to the study.

However, women with diagnosed celiac disease were no more likely to have stillborn babies than women without celiac disease. And none of the women with celiac disease died.

Large US study

The study by researchers from the Cleveland Clinic and colleagues was based on a review of hospital-stay records in the National Inpatient Sample, the largest database in the United States of privately and publicly insured patients who received in-patient hospital care. It contains data from approximately 8 million hospital stays each year.

Previous studies that linked celiac disease to poor maternal, obstetric and neonatal results were done with European populations or in small numbers, leading researchers to design a study with a large, US population.

They reviewed the records of all pregnant women who delivered babies from 2015 to 2019. By using the international classification of disease codes for celiac disease entered into hospital records, they identified about 11,000 women with celiac disease who had babies.

Undiagnosed celiac disease in pregnant women was not addressed in the US study. A previous study done in Denmark found that women with undiagnosed celiac disease have a greater chance of having stillbirths, miscarriages and other pregnancy complications compared to both women who have been diagnosed and the general population.

Characteristics of pregnant women with celiac disease

In the US study, pregnant women with celiac disease were more likely to be white and older than pregnant women who did not have celiac disease. Nearly 90 percent of the women were white, while about 2 percent were Black and about 6 percent Hispanic.

Women with celiac disease also tended to stay in the hospital longer when giving birth.

“We found that pregnant women with celiac disease were at increased risk of pre-eclampsia, placental diseases, obstetric complications and small for gestational age babies,” the study authors wrote.

High blood pressure and gastroesophageal reflux disease (GERD) during pregnancy also posed increased risk to women with celiac disease compared to women without the condition.

Adherence to gluten-free diet not examined

Whether or how well pregnant women were following the gluten-free diet was not taken into consideration, a significant study limitation. “This is important since prior research shows an association between poor adherence to the gluten-free diet and worse pregnancy outcomes,” the authors noted. The database did not include information on diet adherence.

Additionally, the study did not include data on celiac disease blood test or biopsy results. There was also a possibility that some pregnant women in the database did not have the code for celiac disease in their hospital stay record resulting in them not being counted in the study.

Researchers advised women with celiac disease who are or want to be pregnant to discuss potential pregnancy risks with their obstetrician and gastroenterologist.  Physicians who see maternal complications in their patients with celiac disease should refer them to high-risk maternal-fetal medicine, the authors suggested.

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW are sometimes preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed journal. Studies selected to be presented at DDW go through a review process.

The post US study reveals pregnancy risks for women with celiac disease appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

While oats are safe for most people with celiac disease, some patients react to the protein in oats with acute symptoms and a wheat-like inflammatory response, a study presented at Digestive Disease Week (DDW) found.

But even in those who reacted to the purified avenin protein in oats, no related intestinal damage was found as is the case when those with celiac disease consume gluten, according to the study. 

Exposure to the avenin protein in oats at levels sufficient to activate Interleukin 2 (IL-2) was not associated with intestinal damage after a six-week challenge and acute immunity fell over time, the study by researchers at several Australian institutions found. The results are preliminary and the study is continuing.

The research, presented by Melinda Hardy, PhD, of The Walter and Eliza Hall Institute of Medical Research in Melbourne, is the first controlled immune study of avenin purified from uncontaminated oats. 

Those with celiac disease who do not react to uncontaminated oats can safely continue to include them in their gluten-free diets, said study author Jason Tye-Din, MD, also of the Walter and Eliza Hall Institute of Medical Research.

At the same time, the study results validate that there is a small subset of those with celiac disease who have both symptoms and a measurable immune reaction and need to avoid even uncontaminated oats, he said. “This shows the reaction is not all in their heads,” he noted. 

DDW is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. Studies presented at DDW are sometimes preliminary and give an early look at investigations that are likely to include more details as they progress toward publication in a peer reviewed journal. Studies selected to be presented at DDW go through a review process

Oats safe for most with celiac disease

Purified oats that have not been cross contaminated by wheat gluten while being grown, transported or milled have long been thought to be safe for most of those with celiac disease patients. But the Australian researchers had noted that inflammatory T-cells specific to avenin had been isolated in the blood and intestinal tissue of those with celiac disease.

This finding raised troubling implications about the safety of oats for those who have celiac disease and led to the investigation of whether those susceptible to harm from oats could be identified.

Researchers said their results help resolve the discrepancy between clinical oats safety and oats immunity in celiac disease.  Investigators wrote that it’s “reassuring” to have evidence that in most people with celiac disease, oats do not cause an immunological response at a level the results in damage to the intestine.  

How the study was done

Nearly 30 celiac disease patients, many of whom were experiencing symptoms after consuming uncontaminated oats, were included in the study. 

They were given a series of increasing doses of avenin, followed by an assessment of their symptoms and level of IL-2. Avenin is a water-soluble protein in oats similar to gluten protein in wheat, barley and rye. IL-2 is a sensitive marker of activation of T-cells, which are white blood cells that function as the body’s disease fighting soldiers. In the case of celiac disease, they are incorrectly turned on to attack when the gluten peptides are detected.

In results that researchers called “surprising,” acute IL-2 elevation was found in 11 of 29 study participants, nearly 40 percent, and 60 percent had pain, diarrhea and vomiting, with severity of these symptoms greater in those who had higher levels of IL-2. Tye-Din said the results were not representative of the general celiac disease population due to the large number of patients who chose to participate because of their sensitivity to oats. If the study participants were more representative of the celiac disease population, the numbers would be much lower, he said. 

Five study participants who had elevated IL-2 went on to have a six-week, daily avenin challenge at the highest tolerated dose that triggered IL-2.  Although they had an increase in T-cell response at first, after six weeks these had returned to baseline, with IL-2 response after avenin undetectable. Also, initial acute symptoms resolved. Overall, the avenin was well tolerated and symptoms were short lived after initial reactions.

The study says it is notable that after six weeks of challenge, intestinal biopsies were normal. This contrasted with results for a study participant who did a wheat gluten challenge for six weeks to serve as a control and experienced intestinal damage.

“For regulatory purposes oats should remain a priority allergen to support clear food labeling and informed dietary choices by celiac disease patients,” Hardy said.

The post A small subset of those with celiac disease react to the protein in oat, study confirms appeared first on Beyond Celiac.

By Amy Ratner, director of scientific affairs

Three companies developing celiac disease drugs gave updates on their treatments recently at Digestive Disease Week (DDW). DDW is the largest international annual conference for physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

KAN-101

KAN-101, being tested in clinical trials by Anokion, is designed to restore normal immune tolerance of gluten as a way of treating celiac disease. New data presented at DDW further establishes that KAN-101 induces immune tolerance to gluten, Deborah Geraghty, PhD, Anokion chief executive officer said in a press release.

“KAN-101 could be a game changer for patients, with durable treatment effects observed following administration,” she said.

The data was collected from a Phase 1 trial in which some study participants were given multiple doses of the drug. Celiac disease patients in this group received one of three dose amounts of the drug or a placebo on three separate days over the course of a week. About a week later, they were given a three-day gluten challenge.

Joseph Murray, MD, of the Mayo Clinic and lead investigator in the ACeD (Assessment of KAN-101 in Celiac Disease) trial, presented findings about the movement of KAN-101 through the body and the body’s biological response to the drug. Researchers looked at the way in which KAN-101 was absorbed, distributed, localized in tissue and excreted.

Kan-101 was cleared from circulation in the blood with about six hours across of the dose amounts. The effects of the drug were observed by researchers for up to three weeks after it was given to study participants.

KAN-101 followed by a gluten challenge led to dose-dependent reduction of gluten-induced cytokines, including Interleukin 2 (IL-2), an effect not seen in the placebo group, the study found. IL-2 is a cytokine signaling molecule in the immune system. Previous research has shown a correlation between IL-2 and symptoms in celiac disease patients, including nausea and vomiting.

Cytokines are small, secreted proteins released by cells that have a specific effect on the interactions and communications between cells. When someone has celiac disease, their immune system incorrectly reads gluten proteins as invaders. This miscue triggers T-cells, which function as the body’s disease fighting soldiers, to release cytokines and attack. This attack causes inflammation and tissue destruction.

Kan-101 targets specific receptors on the liver, setting off a cascade of events that re-teach the immune system not to respond to gluten. Unlike broad immunosuppressants, KAN-101 targets only the part of the immune system that drives celiac disease. Anokion is a clinical stage bio-tech company focused on improving the treatment and outcomes of autoimmune disease.

This is the second year Anokion has presented results at DDW. The company launched a second clinical trial in late 2022 and plans to move into Phase 2 study this year.

DONQ52

DONQ52, a drug being developed by Chugai Pharmaceuticals to treat celiac disease by blocking the immune responses that occur, was effective in blocking gluten-specific T-cells, according to early study results presented at DDW.

Early results provide proof-of-concept that DONQ52 can inhibit pathogenic gluten-specific T-cells in celiac disease patients, said Melinda Hardy, PhD, of The Walter and Eliza Hall Institute of Medical Research. Chugai, a Japanese drug and biotech company, is currently recruiting celiac disease patients with the HLADQ 2.5 gene for a Phase 1 clinical trial.

CALY-002

Interim results from a Phase 1 trial of CALY-002, a drug designed to interrupt immune reactions in celiac disease, showed that in healthy volunteers the drug is well tolerated and has a good profile as it moves through the body.

Calypso Biotech, the company developing the drug, is completing recruitment for a clinical trial to study the safety and effectiveness of the drug in celiac disease and eosinophilic esophagitis (EOE) patients.

CALY-002 is an anti-Interleukin-15 (IL-15) monoclonal antibody. Celiac disease and EOE both have significant unmet need where IL-15 plays a role, according to the company. IL-15 is a cytokine that plays a role in celiac disease inflammatory immune response.

Monoclonal antibodies are man-made proteins that can bind to substances in the body. In autoimmune diseases, such as celiac disease, the antibodies are designed to target cytokine proteins that contribute to inflammation.

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