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Jefferson Adams posted an article in Refractory Celiac Disease & Collagenous SprueCeliac.com 04/07/2014 - Histologically non-responsive celiac disease (NRCD) is a potentially serious condition found in celiac disease patients who suffer persistent villous atrophy despite following a gluten-free diet (GFD). Currently, the only way to monitor patient progress rely on invasive and costly serial duodenal biopsies. Looking for better options, a team of researchers recently set out to identify antibody biomarkers for celiac disease patients that do not respond to traditional therapy. The research team included B. N. Spatola, K. Kaukinen, P. Collin, M. Mäki, M. F. Kagnoff, and P. S. Daugherty. They are affiliated with the Department of Chemical Engineering, University of California, Santa Barbara in California, the Department of Gastroenterology and Alimentary Tract Surgery and the Center for Child Health Research at the University of Tampere and Tampere University Hospital in Tampere, Finland, with the Department of Medicine at Seinäjoki Central Hospital in Seinäjoki, Finland, and with the Laboratory of Mucosal Immunology in the Departments of Medicine and Pediatrics at the University of California San Diego in La Jolla, California. Using flow cytometry to screen bacterial display peptide libraries, the team was able to identify the epitopes specifically recognized by antibodies from patients with NRCD, but not by antibodies from responsive celiac disease patients. By comparing ELISA results for sera from 15 NRCD patients and 45 patients with responsive celiac disease, all on a strict GFD for at least 1 year, the team confirmed that deamidated gliadin was the antigen mimicked by library peptides. They identified the dominant consensus epitope sequence by unbiased library screening QPxx(A/P)FP(E/D). The epitope sequence was highly similar to reported deamidated gliadin peptide (dGP) B-cell epitopes. They also found that anti-dGP IgG measurement by ELISA discriminated between NRCD and responsive celiac disease patients with 87% sensitivity and 89% specificity. Most importantly, they found that dGP antibody levels correlated with the severity of mucosal damage, meaning that IgG dGP levels may be useful in monitoring small intestinal mucosal recovery on a GFD in NCRD patients. The team found that celiac patients with NRCD can be spotted by their increased levels of anti-dGP IgG antibodies even when the patients are following strict gluten-free diets Lastly, they feel that anti-dGP IgG assays may be useful for monitoring mucosal damage and histological improvement in celiac disease patients on a strict GFD. Source: Aliment Pharmacol Ther. 2014;39(4):407-417.
Jefferson Adams posted an article in Refractory Celiac Disease & Collagenous SprueCeliac.com 06/04/2012 - Non-responsive celiac disease is very much what it sounds like: celiac disease where symptoms seem to resist treatment and continue even in the face of a gluten-free diet. A team of researchers recently set out to look for the most likely causes of persistent symptoms in celiac disease patients on a gluten-free diet. The research team included David H. Dewar, Suzanne C. Donnelly, Simon D. McLaughlin, Matthew W. Johnson, H. Julia Ellis, and Paul J. Ciclitira. They are variously affiliated with King's College London, Division of Diabetes and Nutritional Sciences, Department of Gastroenterology, and The Rayne Institute at St. Thomas' Hospital in London. Their goal for the study was to investigate all patients referred to our center with non-responsive celiac disease (NRCD), to establish a cause for their continued symptoms. For their study, the research team assessed all non-responsive celiac disease who were referred to their gastroenterology center over an 18-mo period. They then established the etiology of ongoing symptoms for these patients. For all patients, the team established a thorough case history and conducted a complete examination with routine blood work including tissue transglutaminase antibody measurement. Additionally, each patient was examined by a specialist gastroenterology dietician to try to spot any gaps in their diets, or any hidden sources of gluten consumption. When possible, the team conducted a follow-up small intestinal biopsy, and compared the results against the biopsies from the referring hospital. Patients with persistent symptoms received colonoscopy, lactulose hydrogen breath testing, pancreolauryl testing and a computed tomography scan of the abdomen. The team monitored patient progress over a minimum of two year period. Overall, the team looked at 112 patients with non-responsive celiac disease. They determined that twelve of those did not actually have celiac disease. Of the remaining 100 patients, nearly half, 45%, were not adequately following a strict gluten-free diet. Of these, 24 (53%) were found to be accidentally consuming gluten, while 21 (47%) admitted to not faithfully following a gluten-free diet. Microscopic colitis was found in 12% and small bowel bacterial overgrowth in 9%. Refractory celiac disease was found in 9%. Three of these were diagnosed with intestinal lymphoma. After 2 years, 78 patients remained well, eight had continuing symptoms, and four had died. In most cases of non-responsive celiac disease, the team found a reversible cause can be found in 90%. In the vast number of those cases, continued consumption of gluten was the main cause. The team is proposing the use of an algorithm for further investigation of the matter. Source: World J Gastroenterol. 2012 Mar 28;18(12):1348-56.
Jefferson Adams posted an article in Refractory Celiac Disease & Collagenous SprueCeliac.com 03/18/2009 - A recent study used lactulose hydrogen-breath assays to show that small intestine bacterial overgrowth (SIBO) is likely a routine cause of non-responsive celiac disease. A team of researchers from the Mayo Clinic College of Medicine recently set out to assess the rates and significance of SIBO in celiac disease based on the results of quantitative culture of intestinal aspirate. The team was made up of Alberto Rubio-Tapia, M.D., Susan H. Barton, M.D., Joseph A. Murray, M.D., of the Mayo’s Division of Gastroenterology and Hepatology, and Jon E. Rosenblatt, M.D., of the Mayo’s department of Laboratory Medicine and Pathology. Their efforts were supported by the American College of Gastroenterology (ACG) International Training Grant 2006 (ART) and the NIH grants DK-57892 and DK-070031 (JAM). Currently, the rate of SIBO in celiac disease diagnosed by quantitative culture of intestinal aspirate is not known. The team set out to assess the rate and determine the significance of SIBO in celiac disease based on the results of quantitative culture of intestinal aspirate. The team set out to examine the causes of non-responsive celiac disease by looking at people with celiac disease in whom culture of intestinal aspirate was assessed for the presence of both aerobic and anaerobic bacteria. They defined bacterial overgrowth as culture >105 colony forming units/mL. In all, they evaluated 149 people with biopsy-confirmed celiac disease. They took intestinal aspirate samples from 79 (53%) patients with non-responsive celiac disease, 47 (32%) as initial work-up for mal-absorption, and in 23 (15%) with asymptomatic treated celiac disease. The team diagnosed 14 cases of SIBO (9.3%), nine cases of non-responsive celiac disease (11%), five cases at initial work-up for mal-absorption (11%), and 0 cases in asymptomatic treated celiac disease. Patients with a positive culture showed signs of worse mal-absorption. 67% of patients with both non-responsive celiac disease and bacterial overgrowth showed a coexistent disorder. The results showed that nearly 1 in 10 celiac patients had SIBO as diagnosed by quantitative culture of intestinal aspirate (9.3%). This figure included both patients with symptomatic treated or untreated celiac disease. This shows that SIBO may exist along with other maladies associated with non-responsive celiac disease. Journal of Clinical Gastroenterology: Volume 43(2)February 2009pp 157-161
Am J Gastroenterol. 2002 Aug;97(8):2016-21 Celiac.com 01/29/2004 - According to researchers at the Mayo Clinic in Rochester Minnesota, the main causes of non-responsive celiac disease are: "1) gluten contamination is the leading reason for non-responsive celiac disease; 2) of non-responsive celiac disease cases, 18% are due to Refractory Sprue; and 3) alternative diseases or those coexistent with celiac disease and gluten contamination should be ruled out before a diagnosis of Refractory Sprue is made." The researchers define Refractory Sprue as "failure of a strict gluten-free diet to restore normal intestinal architecture and function in patients who have celiac-like enteropathy," and conducted a study to determine possible causes, including how many people actually have Refractory Sprue compared with how many are diagnosed with it. The researchers examined the medical records of 55 patients who were, between 1997 and 2001, presumed to have non-responsive celiac disease, six of which were later found not to have celiac disease. Of the 49 remaining patients 25 were identified as having gluten contamination in their diet. The researchers add: "Additional diagnoses accounting for persistent symptoms included: pancreatic insufficiency, irritable bowel syndrome, bacterial overgrowth, lymphocytic colitis, collagenous colitis, ulcerative jejunitis, T-cell lymphoma, pancreatic cancer, fructose intolerance, protein losing enteropathy, cavitating lymphadenopathy syndrome, and tropical sprue." I think that it is clear that if you have celiac disease and continue to have symptoms your first step should be to look closely at your diet for any possible gluten contamination. Your next step should be eliminating other common food intolerance items such as cows milk, soy, eggs or corn. -Scott Adams