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Celiac.com 11/30/2015 - A new study by researchers in Italy shows that only a minority of patients who meet clinical criteria for non-celiac gluten sensitivity actually show symptoms when exposed to gluten in a controlled gluten challenge. Why is that? Researchers haven't had much good information on whether symptoms in people who meet clinical diagnostic criteria for non-celiac gluten sensitivity (NCGS) are specifically triggered by gluten. To provide better information, a team of researchers recently set out to assess gluten sensitivity in patients diagnosed with NCGS. The research team includes B. Zanini; R. Basché; A. Ferraresi; C. Ricci; F. Lanzarotto; M. Marullo; V. Villanacci; A. Hidalgo; and A. Lanzini. They are variously affiliated with Department of Gastroenterology, and the Department of Pathology at the University and Spedali Civili of Brescia, Brescia, Italy, and the Department of Food, Environmental and Nutritional Sciences at the University of Milan, Milan, Italy. For their in a double-blind challenge study, their team looked at 31 females and 4 males without celiac disease, who were following a gluten-free diet (GFD). Participants were randomly broken into groups that received either gluten-containing flour or gluten-free flour for 10 days, followed by a 2-week washout period, followed by a switch in gluten-free/non-gluten-free diets. The main outcome measure was the test subjects' ability to identify which flour contained gluten. Secondary outcome measures were based upon Gastrointestinal Symptoms Rating Scale (GSRS) scores. Only 12 participants (34%) classified as having NCGS correctly pointed out the gluten-containing flour. These participants showed much higher average GSRS dimension scores following gluten challenge compared to baseline. The team measured scores for: pain, 1.7 ± 0.8 vs. 2.6 ± 1.0; reflux, 1.6 ± 0.5 vs. 2.2 ± 0.9; indigestion, 1.9 ± 0.7 vs. 3.2 ± 1.1; diarrhea, 1.6 ± 0.7 vs. 2.9 ± 1.5 and constipation, 1.9 ± 0.9 vs. 2.9 ± 1.3. Seventeen participants, nearly half, erroneously considered the gluten-free flour to contain gluten. Their average GSRS dimension scores were significantly higher following gluten-free flour challenge compared to baseline. The scores were: pain, 1.6 ± 0.9 vs. 3.0 ± 0.9; reflux, 1.4 ± 0.5 vs. 2.3 ± 1.1; indigestion, 2.0 ± 1.1 vs. 3.7 ± 1.1; diarrhea, 1.6 ± 0.7 vs. 3.0 ± 1.2 and constipation, 1.6 ± 0.9 vs. 2.6 ± 1.3. The other six participants (17%) were unable to distinguish between the flours. Based on this study, only about one in three patients with clinical non-celiac gluten sensitivity showed an adverse reaction to gluten. Clearly, more needs to be done to determine the exact nature of non-celiac gluten-sensitivity, and to determine what, if anything, may be driving these adverse reactions that can be triggered by non-gluten containing foods. Source: Aliment Pharmacol Ther. 2015;42(8):968-976.

Celiac.com 03/23/2015 - There's been a bit of ping-ponging going on about the status of non-celiac gluten sensitivity as a valid medical condition. Studies have yielded conflicting results, with some supporting, and others negating, the existence of non-celiac gluten-sensitivity. So what's the deal? Does non-celiac gluten sensitivity exist, or not? Researchers and clinicians continue to debate whether people without celiac disease or wheat allergy who consume gluten can experience intestinal and extra-intestinal symptoms attributable to non-celiac gluten sensitivity (NCGS). Taking the latest stab at the problem, a team of researchers recently conducted a randomized, double-blind, placebo-controlled, cross-over trial to determine the effects of administration of low doses of gluten to subjects with suspected NCGS. The research team included A. Di Sabatino, U. Volta, C. Salvatore, P. Biancheri, G. Caio, R. De Giorgio, M. Di Stefano, and G. R. Corazza. They are variously affiliated with the First Department of Internal Medicine at St Matteo Hospital Foundation at the University of Pavia in Pavia, Italy, and with the Department of Medical and Surgical Sciences at St Orsola-Malpighi Hospital at the University of Bologna in Bologna, Italy. For their study, the team enrolled 61 adults without celiac disease or wheat allergy, but who believe that eating gluten-containing food to be causing of their intestinal and extra-intestinal symptoms. The team randomly assigned participants to groups that received either 4.375 g/day gluten or rice starch (placebo) for 1 week, each via gastro-soluble capsules. Study subjects spend one week on a gluten-free diet, and then switched groups. The primary outcome was the change in overall (intestinal and extra-intestinal) symptoms, determined by established scoring systems, between gluten and placebo intake. A secondary outcome was the change in individual symptom scores between gluten vs placebo. Per-protocol analysis of data from the 59 patients who completed the trial shows that intake of gluten significantly increased overall symptoms compared with placebo (P=.034). Among the intestinal symptoms, abdominal bloating (P=.040) and pain (P=.047) were significantly more severe when subjects received gluten than placebo. Among the extra-intestinal symptoms, foggy mind (P=.019), depression (P=.020), and aphthous stomatitis (P=.025) were also worse when subjects received gluten than placebo. In this cross-over trial, subjects with suspected NCGS saw significantly more severe symptoms during 1 week of intake of small amounts of gluten, compared with placebo. So, at least for now, the NGCS ball seems to be back in the court that considers it a valid medical condition. Source: Clin Gastroenterol Hepatol. 2015 Feb 19. pii: S1542-3565(15)00153-6. doi: 10.1016/j.cgh.2015.01.029. Clinical trial no: ISRCTN72857280.

Celiac.com 12/29/2014 - While the immune response to gluten proteins in celiac disease has been well researched, and is pretty well understood, researchers really don’t know much about the immune response to non-gluten proteins in wheat. A team of researchers recently set out to determine the level and molecular specificity of antibody response to wheat non-gluten proteins in celiac disease. The research team included Sina Huebener, Charlene K. Tanaka, Melanie Uhde, John J. Zone, William H. Vensel, Donald D. Kasarda §, Leilani Beams, Chiara Briani, Peter H. R. Green, Susan B. Altenbach, and Armin Alaedini. They are variously affiliated with the Department of Medicine at Columbia University in New York, New York, USA, the Celiac Disease Center at Columbia University in New York, New York, USA, the Western Regional Research Center, Agricultural Research Service of the United States Department of Agriculture in Albany, California, USA, the Department of Dermatology at the University of Utah in Salt Lake City, Utah, USA, the Department of Neurosciences at the University of Padova, in Padova, Italy, and the Institute of Human Nutrition at Columbia University in New York, New York, USA. Together, the team screened blood samples from celiac patients and control subjects for IgG and IgA antibody reactivity to a non-gluten protein extract taken from the wheat cultivar Triticum aestivum Butte 86. They also analyzed the antibodies for reactivity to specific non-gluten proteins by two-dimensional gel electrophoresis and immunoblotting. They used tandem mass spectrometry to identify any immuno-reactive molecules. They found that, compared with healthy control subjects, celiac patients showed significantly higher levels of antibody reactivity to non-gluten proteins. The main immuno-reactive non-gluten antibody culprit proteins were serpins, purinins, α-amylase/protease inhibitors, globulins, and farinins. Assessment of reactivity toward purified recombinant proteins further confirmed the presence of antibody response to specific antigens. These results show that, in addition to the well-understood immune reaction to gluten, people with celiac disease experience reactions to a number of non-gluten proteins of wheat. The short take away is that the bodies of people with celiac disease show clear immune responses, not just to gluten proteins in wheat, but to non-gluten proteins, as well. Source: J. Proteome Res., DOI: 10.1021/pr500809b

Celiac.com 07/01/2009 - Immunity to food allergens such as gliadin, or the proteins in cow's milk is central to prevention of certain diseases via an appropriate restriction diet. Detecting heightened levels immune reactions to antigen(s) in food is important because scientists have credible reports of certain health disturbances, such as celiac disease, and some pre-malignant conditions, such as monoclonal gammopathy of undetermined significance (MGUS), disappearing under a regimen of appropriate food restriction diets. Only a small number of genetically predisposed individuals show a toxic small bowel mucosa reaction to gliadin. Since levels of immunogenic gliadin may vary between different wheat species, a team of researchers first set out to assess immunogenic gliadin levels in ten bread wheat types and in three strains of commercially grown durum wheat. The team was made up of Aleksandra Konic-Ristic, Dejan Dodig, Radmilo Krstic, Svetislav Jelic, Ivan Stankovic, Aleksandra Ninkovic, Jelena Radic, Irina Besu, Branka Bonaci-Nikolic, Njegica Jojic, Milica Djordjevic, Dragan Popovic, and Zorica Juranic. They were spurred by previous studies that showed sera of some of multiple myeloma (MM) patients with elevated levels of anti-gliadin IgA, without enhanced levels of anti-gliadin IgG antibodies, as determined by commercial ELISA test. They designed their own specifically to uncover any hidden anti-gliadin IgG immunoreactivity in patient blood samples. For this reason, researchers tested blood of both MM patients and celiac disease patient for immunoreaction with native gliadin isolated from regional wheat species used for bread and pasta making. The team isolated gliadin from wheat flour by two step 60% ehanolic extraction. They determined gliadin levels by commercial R5 Mendez Elisa using PWG gliadin as the standard. Results showed immunogenic gliadin content varies between 50.4 and 65.4 mg/g in bread wheat samples and between 20 and 25.6 mg/g in durum wheat samples. Anti-gliadin IgA and IgG immunoreactivity of patients'sera in (IU/ml) was first measured by commercial diagnostic Binding Site ELISA test, and then additionally by non-commercial ELISA tests, using standardized ethanol wheat extracts -gliadin as the antigen. In both patient groups, IgA immunoreactivity to gliadin from different samples was almost homogenous and in correlation with results from commercial test, except for one IgA(lambda) myeloma patient. However, results for IgG immunoreactivity were less homogeneous. Results showed different immunogenic gliadin epitope levels in various species of wheat. They also point to a need for developing a new standard antigen, a representative mixture of gliadin isolated from local wheat species used for bread production in corresponding geographic region for ELISA diagnostic tests. Source: BMC Immunology 2009, 10:32