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Found 2 results

  1. Celiac.com 04/02/2018 - Exactly how hard is it for people with celiac disease to faithfully follow a gluten-free diet? Anyone who’s ever tried to completely avoid gluten for any length of time likely has a story to tell about accidental gluten consumption, and the consequences that follow. It’s not at all uncommon for gluten-free celiacs to be exposed to low levels of gluten that can trigger symptoms and cause persistent intestinal histologic damage. To gain an understanding of gluten consumption across a wide population of celiac patients, a team of researchers recently set out to determine how much gluten people eat when they are trying to follow a gluten-free diet. The team included Jack A Syage, Ciarán P Kelly, Matthew A Dickason, Angel Cebolla Ramirez, Francisco Leon, Remedios Dominguez, and Jennifer A Sealey-Voyksner. They are variously affiliated with ImmunogenX in Newport Beach, CA, the Beth Israel Deaconess Medical Center at Harvard Medical School in Boston MA, and with Biomedal in Seville, Spain. The team began by analyzing data from previous clinical studies. That meta-analysis focused on data from a clinical study of gluten in stool and urine in celiac patients, a second study on non-celiac populations; and an analysis of data from trials for the investigational therapeutic latiglutenase. As part of the stool and urine studies the team included controlled gluten challenges. They then applied a calibration factor that allowed normal ingestion of gluten to be computed from the urine and stool measurements. They determined gluten consumption by estimating how much gluten was eliminated from patients’ diets due to a trial effect that resulted in improved histology, even in the placebo group. Using the stool test, the team estimated the average inadvertent exposure to gluten by celiac disease individuals on a GFD to be about 150–400 mg/d, while they estimated the median exposure to be about 100–150 mg/d. Using the urine test, those numbers showed an average exposure of about 300–400 mg/d, with a median of about 150 mg/d. Meanwhile, data analyses showed that celiac patients with moderate to severe symptoms showed that patients ingested substantially more than 200 mg/d of gluten. The data indicate that many gluten-free celiacs regularly consume enough gluten to trigger symptoms and perpetuate gut damage. Source: The American Journal of Clinical Nutrition, Volume 107, Issue 2, 1 February 2018
  2. Celiac.com 06/27/2017 - What can gene cells tell us about potential gut damage in people with celiac disease? Can they be harnessed to paint an accurate picture of what's going on in the gut? A team of researchers recently set out to study autoimmunity and the transition in immune cells as dietary gluten induces small intestinal lesions. Specifically, they wanted to know if a B-cell gene signature correlates with the extent of gluten-induced gut damage in celiac disease. The research team included Mitchell E. Garber, Alok Saldanha, Joel S. Parker, Wendell D. Jones, Katri Kaukinen, Kaija Laurila, Marja-Leena Lähdeaho, Purvesh Khatri, Chaitan Khosla, Daniel C. Adelman, and Markku Mäki. They are variously affiliated with the Alvine Pharmaceuticals, Inc, San Carlos, California, the Department of Chemistry, Stanford, California, the Institute for Immunity, Transplantation and Infection, Stanford, California, the Division of Biomedical Informatics, Department of Medicine, Stanford, California, the Department of Chemical Engineering, Stanford, California, the Stanford ChEM-H, Stanford University, Stanford, California, the InterSystems Corporation, Cambridge, Massachusetts, the Lineberger Comprehensive Cancer Center, Chapel Hill, North Carolina, the Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, the EA Genomics, Division of Q2 Solutions, Morrisville, North Carolina, the Tampere Center for Child Health Research, Tampere, Finland, the University of Tampere Faculty of Medicine and Life Sciences, Tampere, Finland, the Department of Pediatrics, Tampere, Finland, the Department of Internal Medicine, Tampere, Finland, Tampere University Hospital, Tampere, Finland, and with the Division of Allergy/Immunology, Department of Medicine, University of California San Francisco, San Francisco, California. The team looked at seventy-three celiac disease patients who followed a long-term, gluten-free diet. Those patients ingested a known amount of gluten daily for 6 weeks. Prior to the study, the team took a peripheral blood sample and intestinal biopsy specimens, then did the same after 6 weeks of gluten challenge. To accurately quantify gluten-induced intestinal injury, they reported biopsy results on a continuous numeric scale that measured the villus-height–to–crypt-depth ratio. As patient gut mucosa remained either relatively healthy or else deteriorated under the gluten challenge, the team isolated pooled B and T cells from whole blood, and used DNA microarray to analyze RNA for changes in peripheral B- and T-cell gene expression that correlated with changes in villus height to crypt depth. As is often the case with celiac disease, intestinal damage from the gluten challenge varied considerably among the patients, ranging from no visible damage to extensive damage. Genes differentially expressed in B cells correlated strongly with the extent of gut damage. Increased B-cell gene expression correlated with a lack of sensitivity to gluten, whereas their decrease correlated with gluten-caused mucosal damage. The the correlation with gut damage was tied to a core B-cell gene module, representing a subset of B-cell genes analyzed. In patients with little to no intestinal damage, genes comprising the core B-cell module showed an overall increase in expression over the 6 week period. This suggests that B-cell immune response in these patients may be a reaction to promote mucosal homeostasis and circumvent inflammation. The idea that B-cell gene signature can reveal the extent of gut damage in celiac patients is intriguing. Clearly more research is needed to determine how this revelation might be harnessed to improve the evaluation and treatment of celiac disease. Source: Cell Mol Gastroenterol Hepatol. 2017 Jul; 4(1): 1–17. Published online 2017 Jan 28. doi: 10.1016/j.jcmgh.2017.01.011. PMCID: PMC5413199
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