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Celiac.com 09/30/2021 - Anemia is common in children with celiac disease, but the details of how the disease develops in the gut remain obscure. One possible explanation could be an abnormal expression of duodenal iron transport proteins. However, the results have so far been unclear. To get a better understanding of the issue, a team of researchers recently set out to compare immunohistochemical stainings of duodenal cytochrome B (DCYTB), divalent metal transporter 1 (DMT1), ferroportin, hephaestin and transferrin receptor 1 (TfR1) in duodenal biopsies between 27 children with celiac disease and duodenal atrophy, 10 celiac autoantibody-positive children with potential celiac disease and six autoantibody-negative control children. The team looked at data for forty-three subjects, twenty-three with anemia, and twenty without. For both groups, the team evaluated expressions of iron proteins with respect to saturation and amount of stained area or stained membrane length of the enterocytes. The team's results showed an increase in the stained area of ferroportin, and a decrease in the saturation of hephaestin, in celiac patients versus control subjects. Meanwhile, the team found no differences in the expression of transporter protein between anemic and non-anemic patients. The present results indicate a change in ferroportin and hephaestin proteins in children with histologically confirmed celiac disease that is independent of iron status. Being able to spot celiac disease in children using simple stain reactions could be helpful to improving early diagnosis of celiac disease. Read more at mdpi.com. The research team included Marleena Repo, Markus Hannula, Juha Taavela, Jari Hyttinen, Jorma Isola, Pauliina Hiltunen, Alina Popp, Katri Kaukinen, Kalle Kurppa, and Katri Lindfors, and Isabel Comino. They are variously affiliated with the Tampere Centre for Child Health Research, Tampere University and Tampere University Hospital in Tampere, Finland; the Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; the Faculty of Medicine and Health Technology and BioMediTech Institute, Tampere University in Tampere, Finland; the Central Finland Central Hospital in Jyväskylä, Finland; the Laboratory of Cancer Biology, Faculty of Medicine and Health Technology, Tampere University in Tampere, Finland; Jilab Inc., in Tampere, Finland; the National Institute for Mother and Child Health, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania; the Department of Internal Medicine, Tampere University Hospital, Tampere, Finland; and the Department of Pediatrics, Seinäjoki Central Hospital and University Consortium in Seinäjoki, Finland

Celiac.com 04/01/2020 - Some people with celiac disease have symptoms even when they follow a gluten-free diet. Even though the most likely culprit in these cases is cross-contamination, or some other type of food sensitivity, some people have suggested that the problem may have to do with certain foods that trigger a celiac-like gut reaction. But, is that really true? A few years back, a team of researchers set out to figure out if such symptoms might come from either cross-contamination with gluten-containing foods, or cross-reactivity between α-gliadin and non-gluten foods eaten as part of an otherwise gluten-free diet. Researcher Aristo Vojdani, and colleagues with the Immunosciences Lab used ELISA and dot-blot to gauge the reactivity of affinity-purified polyclonal and monoclonal α-gliadin 33-mer peptide antibodies against gliadin and other food antigens often eaten by celiacs who are following a gluten-free diet. The team also assessed the immune reactivity of these antibodies with various tissue antigens. According to their results, these antibodies to cow’s milk, milk chocolate, milk butyrophilin, whey protein, casein, yeast, oats, corn, millet, instant coffee and rice, triggered significant immune reactivity. These results seemed to confirm that certain foods might be "cross-reacting," and triggering celiac-like symptoms in celiac patients on a gluten-free diet. Questions About Vojdani Methodology Taken at face value, the 2013 Vojdani study would seem to support the idea of otherwise gluten-free foods being cross-reactive, and causing celiac-like symptoms in people with celiac disease. However, a 2019 review of that study by Christina L. Graves Ph. D, with the University of North Carolina at Chapel Hill Department of Biology, casts serious doubt on the methodology and findings of the Vojdani study. Ms. Graves' review, 19 Gluten Cross-Reactive Foods Busted Myth, appears at Paleofoundation.com, and she really highlights the flaws in the Vojdani study, and they are many. Also, for something as simple as corn zein, "...celiac disease-specific antibodies don’t appear to cross-react to corn zein. The rice/gluten cross-reactive study cited by Vojdani & Tarash 2013 is specific for IgE mediated responses, whose dominant epitopes are different than the epitopes recognized by anti-α-gliadin antibodies presented in this study. Graves takes care not to step on too many toes by noting that she is only seeking "to highlight the importance of being rigorous with our own research and reporting within the ancestral health community and to highlight that the rationale for the avoidance of some foods may have arrived through the inflated interpretation of inconclusive results." With respect to the types of tests used to show cross-rectivity, Graves adds "The Celiac Disease Center does not currently recognize Enterolabs or Cyrex stool tests for cross-reactivity (or for celiac disease for that matter). [20] Simply, they are “not sensitive or specific enough” and just haven’t held water (yet) in the scientific arena." Graves may tread lightly in her comments, but her methodical take down of the Vojdani study casts serious doubt on the study's methods, and conclusions, about cross-reactivity. Moreover, there has been no substantial confirmation of the Vojdani findings since the original publication, and there has, so far, been no credible rebuttal to Graves' finding regarding the study. Thus, it is sensible to conclude that Graves is correct, the Vojdani study methods and conclusions are seriously flawed, and that there is no good data to support to claims that cross-reactivity in certain non-gluten foods can trigger celiac-like symptoms in people with the disease. Put simply, until we get more convincing study, with solid evidence to the contrary, there is no good evidence to support the idea of non-gluten cross-reactivity in people with celiac disease. Read 19 Gluten Cross-Reactive Foods Busted Myth by Christina L. Graves Ph. D at Paleofoundation.com. Read the original Vojdani Study in Food and Nutrition Sciences 04(01):20-32 · January 2013.

Celiac.com 12/31/2012 - In people with celiac disease, eating wheat, barley, or rye triggers inflammation in the small intestine. Left unchecked, this inflammation causes the gut damage that is associated with untreated celiac disease. Specifically, the storage proteins in these grains (gluten) trigger an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. Researchers actually have a pretty good understanding of this aspect of celiac disease, part of a process called adaptive immunity. However, there has been some research that suggests that gluten proteins might trigger an immune response in people who do not have celiac disease, and who do not carry the HLA-DQ2 or HLA-DQ8 genetic markers that predispose them to developing celiac disease. Such a response is part of a process called innate immunity, and is far less understood than the adaptive immunity process. The innate immune system provides an early response to many microbial and chemical stimuli and is critical for successful priming of adaptive immunity. To better understand the relationship between adaptive immunity and innate immunity in celiac disease, a research team recently set out to determine if gliadin digests might induce innate immune responses in celiac and non-celiac individuals. Specifically, they wanted to know if wheat amylase trypsin inhibitors drive intestinal inflammation, and if so, by what receptor mechanism. The research team included Yvonne Junker, Sebastian Zeissig, Seong-Jun Kim, Donatella Barisani, Herbert Wieser, Daniel A. Leffler, Victor Zevallos, Towia A. Libermann, Simon Dillon, Tobias L. Freitag, Ciaran P. Kelly, and Detlef Schuppan. They are affiliated variously with the Division of Gastroenterology and the Proteomics and Genomics Center at Beth Israel Deaconess Medical Center at Harvard Medical School in Boston, with the Department of General Pediatrics and the Department of Internal Medicine I at the University Medical Center Schleswig-Holstein Kiel in Kiel, Germany, the Department of Experimental Medicine at the University of Milano-Bicocca in Milan, Italy, the German Research Center for Food Chemistry in Garching, Germany, the Hans-Dieter-Belitz-Institute for Cereal Grain Research in Freising, Germany, the Division of Molecular and Translational Medicine in the Department of Medicine I at Johannes Gutenberg University in Mainz, Germany, and with the Department of Bacteriology and Immunology at the Haartman Institute at the University of Helsinki in Finland. A number of earlier studies (Molberg et al., 1998; Anderson et al., 2000; Shan et al., 2002) have found HLA-DQ2– and HLA-DQ8–restricted gluten peptides that trigger the adaptive immune response in people with celiac disease. However, only 2–5% of individuals who show these HLAs develop celiac disease, which means that other factors, especially innate immune activation, are at play in the generation of celiac disease. Responsive innate cells are primarily macrophages, monocytes, DCs, and polymorphonuclear leukocytes that by means of their pattern-recognition receptors, such as TLRs, trigger the release of proinflammatory cytokines and chemokines, resulting in recruitment and activation of additional inflammatory cells (Medzhitov, 2007). Earlier studies (Maiuri et al., 2003) showed that peptides p31-43 or p31-49 from α-gliadin, that lack adaptive stimulatory capacity, triggered innate immune reactions by inducing IL-15 and Cox-2 expression in patient biopsies, and MHC class I polypeptide–related sequence A (MICA) on intestinal epithelial cells (Hüe et al., 2004). However, these studies have proven difficult to reproduce in cell culture, and researchers could not identify any specific receptor responsible for the observed effects. In a subsequent study, gliadin, in cell culture, reportedly triggered increased expression of co-stimulatory molecules and the production of proinflammatory cytokines in monocytes and DCs (Nikulina et al., 2004; Cinova et al., 2007). Two other studies (Thomas et al., 2006; Lammers et al., 2008) implicated the chemokine receptor CXCR3 in increased intestinal epithelial permeability upon gliadin challenge in a MyD88-dependent manner. However, those studies failed to reproducibly identify a specific gliadin peptide as the trigger. So far, no clear picture of the role of the innate immune system in celiac disease has emerged. In this study, the researchers show that members of the non-gluten α-amylase/trypsin inhibitors (ATIs), CM3 and 0.19, pest resistance molecules in wheat and related cereals, are strong triggers of innate immune responses in human and murine macrophages, monocytes, and dendritic cells. Their results show that ATIs activate the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients’ biopsies. They also show that mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders. The findings of this study mean that the proteins in wheat may trigger immune reactions not just in people with celiac disease, but in people without celiac disease, and that these reactions may be actively contributing to the development of numerous other intestinal and non-intestinal immune disorders. That's a pretty big deal. Stay tuned to see how future studies elaborate these findings. Read the entire study in the Journal of Experimental Medicine. Source: J Exp Med. 2012 Dec 17;209(13):2395-408. doi: 10.1084/jem.20102660