Researchers describe screening for celiac disease and measurement of intestinal damage
By Amy Ratner, director of scientific affairs
In the first study of its kind in the United States, Marisa Gallant Stahl, MD, of Children’s Hospital Colorado, set out evaluate the impact of celiac disease on the health and quality of life of children who were identified through an earlier mass-screening program.
In the screening of 10,000 children, 242 or 2.4 percent, had an initial positive celiac disease test. Of the 185 children who returned for follow-up, 149 had a positive confirming test. Of those, 62 were seen by a gastroenterologist and 39 went on to be diagnosed with celiac disease. Since these children had no obvious symptoms of celiac disease, they would be unlikely to be diagnosed otherwise, said Stahl, recipient of the 2019 SSCD/Beyond Celiac Early Career Investigator Award
She was one of five scientists who presented updates at the Beyond Celiac Research Summit on their work being funded by Beyond Celiac. Jocelyn Silvester, MD, director of research at the Celiac Disease Program at Children’s Hospital, recipient of the 2019 Pilot and Feasibility Award also spoke at the summit. (For details on work by Paul Klenerman, MD, and Michael Fitzpatrick, MD, of the University of Oxford, UK, and Iain Croall, PhD, of Sheffield University, UK, see part 1 of summit coverage.)
In her follow-up study at the Colorado Center for Celiac Disease, 42 of the children diagnosed with celiac disease through screening were evaluated for growth, symptoms, results of blood tests, including anti-tissue transglutaminase, vitamins and minerals, and health-related quality of life. Ten of the children who had initially enrolled in the study did not complete follow-up. Those lost to follow up were more likely to be older, male, of non-white race, from less affluent households and insured by Medicaid.
“It is important to offer support and resources for racial and ethnic minorities and lower incomes groups as they were more often lost to follow-up,” Stahl said, describing one of the study conclusions.
Many children who reported having no symptoms on a shorter questionnaire filled out at screening later identified symptoms on a more detailed list that was part of the follow-up study. Symptoms new to the list included nausea, brain fog, dizziness, headaches, irritability, joint pain, fractures, delayed puberty and dental problems.
The evolution of symptoms is complex, with most but not all the children getting better on the gluten-free diet, the study concludes. Other conclusions related to the gluten-free diet are that iron deficiency is common in diagnosed children and improves with the gluten-free diet and most children in the study on follow-up had reports of following the diet well.
In conclusions regarding health-related quality of life, the study found that screening diagnosis and treatment with the gluten-free do not seem to be associated with increased anxiety and depression, and overall quality of life overall seems to improve, but may be age dependent.
“Overall, screening seems to be beneficial, but more personalized approaches with behavioral support are needed for disease management to reap the most benefit,” Stahl said. Further study is needed to determine the cost-effectiveness of screening, to compare those identified by mass screening to those identified through more targeted screening and to see if initial symptoms correlate with anxiety, depression and quality of life, she noted.
A biopsy to examine the lining of the small intestine is currently the gold standard for diagnosis of celiac disease in adults and children in the United States. Samples taken during the biopsy are used to determine if the lining of the intestine is healthy or if there is damage to the absorbing finger-like projections, called villi, which is characteristic of celiac disease.
Bur visual inspection of biopsy samples under the microscope is the same method developed more than 50 years ago, leading Silvester to investigate improved methods to evaluate biopsy samples and assess celiac disease activity.
She noted in her summit presentation that both qualitative and quantitative evaluation of biopsies by a pathologist have limitations. For example, qualitative review is highly subjective, while quantitative assessment is very time consuming.
In her study, Silvester is using RNA sequencing of a series of biopsies collected from 20 adults with celiac during an earlier gluten-challenge study. Preliminary data show that transcriptomics, the study of all ribonucleic acid (RNA) molecules within a cell, of intestinal biopsies can identify genes that correlate to inflammation caused by gluten and structural changes in the villi.
“Structural and functional changes of the intestinal epithelium in active celiac disease are associated with a characteristic gene expression pattern with distinct and identifiable subsets of genes whose expression levels correspond to Intraepithelial lymphocytosis, villous height and crypt depth,” Silvester said.
Additionally, the study will check the accuracy of the sequencing method on biopsies previously taken for diagnosis and follow-up on another group of patients. She will be able to compare biopsies taken when gluten was in the diet and after a gluten-free diet was being followed