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  • Jefferson Adams
    Jefferson Adams

    Researchers Find Key Gene Locus Behind Progression from Celiac to Refractory Celiac Disease

    Reviewed and edited by a celiac disease expert.

      Researchers have discovered that a gene locus at 7p14.3 predisposes progression from celiac disease to refractory celiac disease.

    Caption: Image: CC--Elentir

    Celiac.com 09/05/2018 - About one out of every twenty celiac patients fails to respond to a gluten-free diet, and goes on to develop refractory celiac disease (RCD). RCD is a serious condition marked by appearance of intraepithelial T lymphocytes. Depending on the phenotype of the lymphocytes, people develop either RCD I or RCD II. Patients with RCD type II (RCDII) show clonal expansions of intraepithelial T lymphocytes, and face an especially poor prognosis. Just over half of these patients will die within five years of onset due to aggressive enteropathy-associated T-cell lymphoma. 

    At this time, researchers don’t know whether genetic variations might play a role in the severe progression from celiac disease to RCDII. A team of researchers recently set out to try to get some answers.  The team began by conducting the first genome-wide association study to identify the causal genes for RCDII, along with the molecular pathways at play in cases of RCDII. 

    For their genome-wide association study, the team used 38 Dutch patients with RCDII, and replicated the 15 independent top-associated single nucleotide polymorphism (SNP) variants (P<5×10) in 56 independent French and Dutch patients with RCDII.

    The team found that, after replication, SNP rs2041570 on chromosome 7 was significantly associated with progression to RCDII (P=2.37×10, odds ratio=2.36), but not to celiac disease susceptibility. They also found that SNP rs2041570 risk allele A was associated with lower levels of FAM188B expression in blood and small intestinal biopsies. Stratifying RCDII biopsies by rs2041570 genotype revealed differential expression of innate immune and antibacterial genes that are expressed in Paneth cells.

    The team’s efforts resulted in the identification of a new SNP associated with the severe progression of celiac disease to RCDII.  Their data suggest that genetic susceptibility to celiac disease might be unrelated to celiac progression to RCDII, and suggests that Paneth cells might play a role in RCDII progression.



    The research team included B Hrdlickova, CJ Mulder, G Malamut, B Meresse, M Platteel, Y Kamatani, I Ricaño-Ponce, RLJ van Wanrooij, MM Zorro, M Jan Bonder, J Gutierrez-Achury, C Cellier, A Zhernakova, P Nijeboer, P Galan, S Withoff, M Lathrop, G Bouma, RJ Xavier, B Jabri, NC Bensussan, C Wijmenga, and V Kumar. They are variously affiliated with the Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Department of Gastroenterology, VUMC, Amsterdam, The Netherlands, INSERM U1163, Imagine Institute and Paris Descartes University, the Department of Gastroeneterology, Georges Pompidou European Hospital, the Paris 13 University Sorbonne Paris Cité, UREN, Inserm (U557), Inra (U1125), Cnam, Bobigny, France, the scientific director of McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada, the Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, the Department of Medicine, University of Chicago, Chicago, Illinois, USA., and the K.G. Jebsen Coeliac Disease Research Centre, Department of Immunology, University of Oslo, Norway.

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    Interesting article encapsulating RCD types I and II.

    I wish those who suffer celiac reactions, but refuse to & yet continue to ingest gluten/gliadin poisons would listen up. I know of teens who suffers from herpetiform lesions in response to gluten containing foods, & treats the symptoms not the cause.  Others suffering from severe abdominal pain after gluten ingestion say they are literally; "Hooked on bread".

    The extent of damage to the gut from gluten/gliadin is significant. Did "plant geneticists" ever imagine the ramifications of "modern" wheat? Were they aware of the cross-reactor response to Yeast-Egg-Dairy & Coffee?  Were they aware that a damaged gut cannot tolerate the residual toxins in chemically-extracted oils?  Were they aware that a damaged gut cannot tolerate "nitrates" even naturally occurring/concentrated forms such as celery powder? 

    Just how far has science brought us wherein it is "scrambling" to find a way out of the quagmire that it created? I look at the manufactured food labels and weep.  There is always a cross-reactor or preservative within them.  As I read the ingredients, I remember the stories of the youngsters to whom I spoken as they reveal their ongoing "undiagnosed" GI conditions that plaque their lives. Will they be a number in the increasing gastric cancer rate in youth? I ponder these things and weep for the children.


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    I have had Celiac's for 13 years and  I am at the point where I can't even eat any kind of gluten floor because it bloats my stomach. I am really only eating meat and veggies. I can't find any Dr to help me here in town. I to have hepiformis rash


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  • About Me

    Jefferson Adams is Celiac.com's senior writer and Digital Content Director. He earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in science, scientific methodology, biology, anatomy, medicine, logic, and advanced research. He previously served as SF Health News Examiner for Examiner.com, and devised health and medical content for Sharecare.com. Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

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