A recap of notes, experiences, and meetings by Dr. Jingqing Zhang, our Lead Scientist.
I went to the Digestive Disease Week on May 16-19th in Washington, DC. The conference gathered leading physicians and doctors on all types of digestive diseases, including Deliac disease, gluten-intolerance, Inflammatory Bowel Disease (IBD), various gastrointestinal cancers, and many others.
The most interesting session I went to was “Celiac Disease – Which Factors Are At Play in Childhood That Can Increase the Risk To Develop the Disease in Adulthood?”, moderated by two leading Celiac disease experts, Dr. Stefano Guandalini, head of the University of Chicago Celiac Disease center, and Dr. Daniel Leffler, the director of clinical research, the Celiac Center at Beth Israel Deaconess Medical Center. The session focused on investigating both genetic and environmental factors that may contribute to Celiac disease. Four leading researchers in the field presented their work, followed by a panel discussion.
Female children with genetic disposition of homozygous DQ2 are far more likely to develop Celiac disease than others. During this session, Dr. Edwin Liu from Children’s Hospital Colorado presented an interesting multi-center study, named TEDDY, funded by the NIH, the American Diabetes Research Foundation, and the CDC, where researchers are investigating genetic, environmental and gestational factors that contribute to the onset of Celiac disease. This study is focused on children with a family history of Celiac disease, and researchers are performing genetic typing on them, specifically looking at two Celiac disease related genetic predispositions, HLA-DQ2 and HLA-DQ8. These haplotypes are known to increase the risks of Celiac disease, and we also know that DQ2 and DQ8 are also found in 30 percent of the general population, but only 3 percent of individuals with these haplotypes develop Celiac disease (Ref. 1). The TEDDY study has found that the risk of Celiac disease very much depends upon the HLA genotype, and the disease can occur at a very early age. Specifically, ~40% children among the study group with homozygous DQ2/DQ2 develop Celiac disease by the age of 8, and the risk decreases to ~10% if they are with heterozygous DQ8/X haplotypes. The study also found that the risk of developing Celiac disease is further influenced by female gender. The study is still on-going, and will have more results to report in the upcoming years.
Two other interesting studies were reported by Dr. Carlo Catassi from the Department of Pediatrics, Università Politecnica delle Marche, Italy and Dr. Luisa Mearin from Leids Universitair Medisch Centrum, Netherlands, both of which have shown a strong gender (female) and genetic relationship with Celiac disease. An earlier study by a Norwegian group in 2013 found an increased risk of Celiac disease in children with a delayed gluten introduction after 6 months, as well as a higher risk in children breastfed after 12 months. Instead, Dr. Catassi’s work (published in the New England Journal of Medicine, 2014) showed that neither the delayed introduction of gluten nor breast-feeding modified the risk of Celiac disease among at-risk infants, although the later introduction of gluten was associated with a delayed onset of disease. In addition, Dr. Mearin’s work (published in the New England Journal of Medicine, 2014) found that the development of Celiac disease is not related to country of origin, family characteristics, rotavirus vaccination, gastrointestinal infections, respiratory infections, or daily gluten intake. Their data also showed that the development of Celiac disease is not related to timing of breastfeeding either. However, females show a much stronger cumulative incidence of Celiac than males (7.2% vs 3.4% by the age of 3, and 14.5% vs 9.9% vs by the age of 5). Similar to Dr. Edwin Liu’s finding, their group also found a strong relationship between the onset of Celiac with homozygous DQ2: 27% of the DQ2/DQ2 develop Celiac by the age of 5, and only a little over 10% of DQ2/X develop by then. Both were multi-year and multi-centered studies, and each enrolled close to 1000 children. While all these are probably bad news for families with genetic predispositions to Celiac disease, these studies for the first time are able to decouple many previously suspected environmental factors from the onset of Celiac disease, which is instrumental. These findings also further emphasize the attention on female children with homozygous DQ2, as this population has a much higher susceptibility to Celiac disease.
Another very interesting session I went to is the “Celiac Disease and Gluten Intolerance Focus Group” breakfast session. Dr. Peter Green, the director of the Celiac Disease center at Columbia University and the president of the North American Society for the Study of Celiac Disease moderated this focus group. The session reviewed most of the Celiac disease and gluten-intolerance related research topics that were submitted to the conference, and Dr. Green then opened discussions to the audience. I found two studies that were particularly interesting. Dr. Peter Green’s group presented a piece of work on widespread contamination of probiotics with gluten, detected by LC-MS. Specifically, 12 out of 22 (55%) probiotics contained gluten. Of these 12 gluten-containing items, 8 (67%) were labeled GF. Of the 15 labeled GF probiotics, 8 (53%) contained gluten, including 2 (13%) that contained gluten at levels > 20 ppm. Another study by Dr. Luc Biedermann’s group at the University Hospital Zurich showed that there is a substantial diagnostic delay in Celiac disease, due to both patient’s and doctor’s delay. They found a mean total diagnostic delay of 6 years and roughly equal fractions of patient’s and doctor’s delay. This is not an exception among the community – there is a general consensus that as the Celiac disease awareness is increasing, average physicians have not been able to catch up with the most recent research on this disease and gluten-intolerance, not to mention that a lot of research still needs to be done on the diseases themselves.
I came to this conference with one agenda in mind, which is to understand the gluten level that would cause a response to those with Celiac disease, as well as in non-celiac gluten sensitivity patients. Basically, what exactly are the ranges of levels that would trigger a gluten response? We are aware of the FDA guideline of 20 ppm and studies that have led to such a ruling, but many consumers have previously come to us and have indicated that they may be responding to a lower level. After talking with a few leading experts in the field during the conference, it has become very apparent that we are still in a black box, and such a study is so much needed. Non-Celiac gluten sensitivity, in particular, although a real condition, lacks biomarkers to track patients or conditions. It is even harder to study these populations.
I am also surprised to find that many physicians have indicated that many of their IBD patients (Crohn’s and Ulcerative Colitis) also have shown various levels of gluten-intolerance, and the patients’ conditions often improved after removing gluten from their diets. However, much of the research on this topic still needs to be conducted, and I am very interested in understanding the level of gluten to cause a response for these patients, and if they are only reacting to wheat, or gluten in general.
Overall, this is a great conference. It is very informative, and has gathered much of the information from the most recent research in many digestive diseases. It also provides a great platform to allow physicians, scientists, and engineers to come together, to come up with solutions all together to prevent, and treat diseases. Nima is also able to connect with many leading physicians in the community, to understand the problems better, and potentially provide a solution to help the patients!