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  • Jefferson Adams
    Jefferson Adams

    Scientists Catch Culprit Oat Peptides That Trigger Celiac Immune Response

    Reviewed and edited by a celiac disease expert.

    Celiac.com 02/29/2016 - Previous studies have shown that oat proteins trigger an adverse anti-33-mer monoclonal antibody reaction that is proportional to the immune responses in terms of T-cell proliferation.

    Photo: CC--Pedro ReynaAlthough there has been some research regarding the impact of these varieties on the adaptive response, researchers still don't know very much about the role of the dendritic cells. A research team recently set out to characterize different oat fractions and to study their effect on dendritic cells from celiac patients.



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    The research team included Isabel Comino, David Bernardo, Emmanuelle Bancel, María de Lourdes Moreno, Borja Sánchez, Francisco Barro, Tanja Šuligoj, Paul J. Ciclitira, Ángel Cebolla, Stella C. Knight, Gérard Branlard and Carolina Sousa.

    They are variously affiliated with the Departamento de Microbiología y Parasitología, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain; the Gastroenterology Unit, Antigen Presentation Research Group, Imperial College London & St Mark′s Hospital, Harrow, United Kingdom; the Hospital Universitario de La Princesa and Instituto de Investigación Sanitaria Princesa (IIS-IP), Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain; the INRA UMR-1095, Clermont-Ferrand, France; the Nutrition and Bromatology Group, Department of Analytical and Food Chemistry, Food Science and Technology Faculty, University of Vigo-Ourense Campus, Ourense, Spain; the Instituto de Agricultura Sostenible (CSIC), Córdoba, Spain; the Division of Diabetes and Nutritional Sciences, King's College London, Gastroenterology, The Rayne Institute, St Thomas' Hospital, London, United Kingdom; and the Biomedal S.L., Sevilla, Spain.

    The team first isolated protein fragments from oat grains and then analyzed them using SDS–PAGE. They then characterized several proteins in the prolamin fraction using immunological and proteomic tools, as well as Nano-LC-MS/MS. These proteins were very similar to α- and γ-gliadin, and showed reactive sequences to anti-33-mer antibody, indicating their potential for causing adverse immune reactions.

    Furthermore, the team found that some of the newly identified oat peptides triggered a range of immune responses on circulating dendritic cells from celiac patients, as compared with healthy controls.

    This is the first study to show that newly identified oat peptides can trigger a range of stimulatory responses on circulating dendritic cells from celiac patients, which highlights the potential of these oat peptides to trigger adverse immune responses in people with celiac disease.

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    How about labeling them gluten free, but possibly causing a reaction in some people. I have a friend who reacted to everything that she ate for longer than a short period of time. Her family ate a huge variety of meats from the regular pork, beef, and chicken to moose, antelope and buffalo with arrowroot flour and other such things and this was over 50 years ago. From what I can see in the literature, the vast majority of celiacs who eat uncontaminated oats have little or no reaction. The important word in that sentence is "uncontaminated". In any industrial scale process, it is hard to believe that some tiny amount might not slip by. That does not mean that every effort should not be taken to make sure of the purity of oats used for various products. If a certain small percentage of celiacs also respond to pure oats, that is a separate issue. That issue should not be ignored and testing should be carried out to make sure that oat products claiming to be gluten free truly are.

     

    As a casual perusal of the many posts on this site will attest, there is a huge range of reactions to a variety of products within just the readers of this site. Attacking individuals for their particular reactions is not useful. People with different reactions from those portrayed in other posts should merely document "their" reactions and not generalize or assume that some other poster is incorrect. The science on most of this is unclear or unreliable, making it difficult for sufferers to make personal decisions other than by experiment. Even those who choose to be purely vegan or ovo-lacto-vegans are challenged by daily decisions when they are away from home. Extended travel as on vacations can prove to be almost impossible to manage properly.

    I am feeling my way, day by day, and hoping that I can survive the huge intrusion into my life that is represented by celiac disease. My thanks go out to all who participate in this site and those who manage the content.

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  • About Me

    Jefferson Adams

    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 2,500 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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  • Related Articles

    Diana Gitig Ph.D.
    Celiac.com 03/14/2011 - It is still a matter of controversy whether or not oats are safe for people with celiac disease. The general consensus at this point seems to be that pure oats are safe for most, but not all, people with celiac. Since oats can easily be contaminated with wheat during harvest, storage, or other stages of processing, it has been stressed that the oats be certified as pure. Although the classic 33-amino acid long oligopeptide that acts as the immunogenic stimulus in gliadin had not yet been found in oats, other peptides isolated from oats do activate T-cells isolated from celiac patients. A new study performed in Spain by Isabel Comino et al. suggests that it is not that some celiac patients can’t tolerate all oats, but rather that all celiac patients can’t tolerate some oats. Their results are reported in the January 2011 issue of GUT: An International Journal of Gastroenterology and Hepatology.
    Dr. Comina and her colleagues examined nine different cultivars of oats. They exposed each of them to a sensitive monoclonal antibody generated to recognize the toxic 33-mer from gliadin, and also measured if each of the oat varieties could elicit an immune response in peripheral blood mononuclear cells from celiac patients. They wanted to see if they could correlate recognition by the monoclonal antibody to induction of a T-cell response, and found that they certainly could.
    The nine varieties of oats segregated neatly into three groups of three varieties each: those for which the antibody had high affinity, low affinity, and no affinity. This affinity was validated by two different experimental methods, so was not an artifact of the technique chosen. When T cells from patients with celiac were exposed to extracts of the oat variety the antibody bound to strongest, they proliferated the most and released interferon-gamma, an immunostimulatory cytokine whose aberrant expression is associated with autoinflammatory disease. In contrast, the oats that didn’t react with the antibody did not elicit these immune responses. The authors note that the avenin – the storage protein in oats – from even the most immunogenic oats they saw bound to this antibody with 40-400 fold less affinity than gliadin (from gluten – the storage protein in wheat).
    This study thus leaves us with two valuable conclusions. One is that some oats are more toxic than others, regardless of their purity. And the other is that reactivity with this antibody can be correlated to toxicity, making it a potential tool for evaluating the toxic gluten content of other food.
    Source:

    Gut doi:10.1136/gut.2010.225268


    Dr. Ron Hoggan, Ed.D.
    This article originally appeared in the Winter 2004 edition of Celiac.com's Journal of Gluten-Sensitivity.
    Celiac.com 09/19/2014 - Experts have decreed that pure oats are safe for people with celiac disease(1,2,3).  The definition of this disease is based on a very specific type of injury to the intestinal wall that heals following the removal of gluten from the diet.  This intestinal damage, called villous atrophy, is caused by the interaction between the immune system and certain proteins found in wheat, rye, and barley.  Identical proteins are not found in oats (although there is also some variation between the protein groups found in wheat, rye, and barley).  Further, many newly diagnosed celiac patients have been shown to recover from their celiac symptoms while eating significant quantities of oats and their intestinal biopsies do not show signs of villous atrophy1 (Admittedly, the quantity of oats consumed by these study subjects does not rival the grain protein consumption in a regular, gluten-laden diet, but the quantity is significant).  Therefore, this food is considered safe for celiac consumption.
    Given these facts, it is not surprising that many gastroenterologists are now recommending that their patients eat oats.  Some claim that patients are more likely to follow a gluten-free diet if that diet allows oats.  Others point to the definition of celiac disease, which clearly requires gluten-induced villous atrophy.  Still others insist that since we now know which proteins cause the villous atrophy, oats must be safe for celiac patients to consume.
    There are several problems with these perspectives, beginning with the assumption that patients will be more compliant with the diet if it includes oats.  I have explored the medical literature and have been unable to find a single study that investigates dietary compliance as a function of including oats in the gluten-free diet.  I’d be happy to hear about such a study.  But until the question is investigated, the assumption is just one more opinion afloat in a sea of unfounded beliefs about grains and diet.
    Many celiac patients experience an addictive element in gluten.  I have long suspected that is the result of morphine-like, opioid peptides found in the digests of gluten(4-8).  Are some peptides from oats capable of producing these opioids?  Has anyone investigated that issue?  Again, I can find no evidence that this issue has been studied.
    Reliance on the biopsy to reveal problems with oat consumption is another relevant problem.  As many of us can attest, and the medical literature reports, gluten challenges that intentionally involve ingestion of relatively large quantities of gluten often fail to reveal villous atrophy for weeks, months, and sometimes, years(9).  Many celiac patients will also agree that despite our best efforts at compliance, gluten sometimes manages to sneak into our diets, particularly in the early months of following the diet.  Yet a second biopsy usually shows dramatic healing of the intestinal wall, despite these dietary errors.  Clearly, the intestinal biopsy is a fairly crude tool for measuring intestinal health.  Its use in exonerating oats thus becomes suspect.  An even more troubling element of this issue is that there are gastroenterologists who are recommending that their patients consume breakfast cereals that contain malt flavoring, because patients consuming such small quantities of malt do not show villous atrophy(10).
    Also troubling is the fact that many of the studies that support the safety of oats have not employed the Marsh system for identifying intestinal injury, a refinement that significantly increases the sensitivity of the intestinal biopsy.
    The greatest weakness of the pro-oats position is the underlying assumption that we fully understand celiac disease and gluten sensitivity.  This is simply not the case.  The research shows that some celiacs do develop symptoms when consuming oats.  While most newly diagnosed celiacs experience reduced symptoms and improved health, this may simply be the result of consuming less grain-derived protein.  Researchers have long known that even partial compliance with the gluten-free diet produces health improvements in celiac patients(11).
    The definition of celiac disease that requires villous atrophy followed the discovery of the beneficial impact of the gluten-free diet by more than 20 years (If in doubt about this point, please refer to the English translation of Dr. Dicke’s Ph.D. thesis at http://www.dangerousgrains.com).  Our current understanding of the disease began with the observed benefits of the gluten-free diet.  Intestinal biopsies were a much later development.
    A similar debate arose regarding the inclusion of wheat starch.  It was long held to be a safe nutrient in the gluten-free diet in many European countries.  In fact, the studies that showed a reduced risk of cancer and a variety of celiac-associated conditions were often conducted among patient groups living where wheat starch was deemed acceptable(12, 13).  Yet when wheat starch consumption was studied in Canada, against a back-drop of zero tolerance, most of the subjects developed signs and symptoms of celiac disease(14).
    Many celiacs and gluten-sensitive individuals know that their symptoms do not fit with the conventional view of celiac disease.  Some of us believe that there is a continuum of severity.  Others believe that there are many sub-types of celiac disease.  Still others believe, me included, that it really doesn’t matter whether a person has intestinal damage.  The important, defining characteristic should be whether a person is mounting an immune response against the proteins in the most common substance in our food supply.  
    Whatever our beliefs we turn to the experts when faced with health concerns and crises.  However, those answers often rely on the medical definition of celiac disease, where villous atrophy heals in response to a gluten-free diet.  In cases where the biopsy was improperly taken, or too few samples were taken, or patchy intestinal lesions were missed, or other forms of gluten-induced ailments are causing symptoms, we may not get answers that aid our health.  Many individuals who are gluten sensitive will be, under such circumstances, dismissed with a diagnosis of IBS.
    Given the facts, we have several hurdles to overcome before we can, in my opinion, render an informed judgment about the safety of oats.  We need a much better understanding of gluten-induced disease in all of its manifestations.  We also need a definition of celiac disease that is more useful to the patient who is experiencing symptoms of gluten sensitivity/celiac disease.  As part of this, we also need a test that is more accurate, and can identify celiac disease after beginning the diet––a challenge that many of us face.  Until we have overcome these hurdles, any pronouncement regarding the safety of oats is premature.
    Further research is, in my opinion, the greatest need of the celiac community.  We need to know more, not just about celiac disease, but about the whole range of nutritional and pathological impacts of eating grains. In my own quest, I have learned from the experiences of other celiac patients.  Each new facet of my own experience has been illuminated by someone else’s story.  I have come to understand ADHD as a frequent companion of celiac disease.  Learning disabilities are also common among celiacs.  Behavioral disturbances are the norm, and speech problems are common.  My understanding continues to grow as I hear from others who struggle with gluten sensitivity.
    Despite its usefulness, this patient-to-patient network of information sharing is not enough.  We need well designed, well executed research.  We need a better understanding of our disease and how to protect future generations from the current, inaccurate assumptions about grains.  The oats question is only one facet of a much larger need for more information and better testing methods.
    Sources:
    Storsrud S, Olsson M, Arvidsson Lenner R, Nilsson LA, Nilsson O, Kilander A.    Adult coeliac patients do tolerate large amounts of oats. Eur J Clin Nutr. 2003 Jan;57(1):163-9. Kilmartin C, Lynch S, Abuzakouk M, Wieser H, Feighery C.  Avenin fails to induce a Th1 response in coeliac tissue following in vitro culture. Gut. 2003 Jan;52(1):47-52. Janatuinen EK, Kemppainen TA, Julkunen RJ, Kosma VM, Maki M, Heikkinen M, Uusitupa MI.  No harm from five year ingestion of oats in coeliac disease. Gut. 2002 Mar;50(3):332-5. Teschemacher H.  Opioid receptor ligands derived from food proteins. Curr Pharm Des. 2003;9(16):1331-44. Review. Yoshikawa M, Takahashi M, Yang S. Delta opioid peptides derived from plant proteins. Curr Pharm Des. 2003;9(16):1325-30. Review. Horvath K, Graf L, Walcz E, Bodanszky H, Schuler D. Naloxone antagonises effect of alpha-gliadin on leucocyte migration in patients with coeliac disease. Lancet. 1985 Jul 27;2(8448):184-5. Zioudrou C, Streaty RA, Klee WA. Opioid peptides derived from food proteins. The exorphins. J Biol Chem. 1979 Apr 10;254(7):2446-9. Hoggan R.  Considering wheat, rye, and barley proteins as aids to carcinogens. Med Hypotheses. 1997 Sep;49(3):285-8. Fukudome S, Yoshikawa M.   Opioid peptides derived from wheat gluten: their isolation and characterization. FEBS Lett. 1992 Jan 13;296(1):107-11. Kuitunen P, Savilahti E, Verkasalo M.  Late mucosal relapse in a boy with coeliac disease and cow's milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. Holmes, et. al. "Malignancy in coeliac disease - effect of a gluten free diet" Gut 1989; 30: 333-338 Holmes GK.  Coeliac disease and malignancy.Dig Liver Dis. 2002 Mar;34(3):229-37 Collin P, Pukkala E, Reunala T.  Malignancy and survival in dermatitis herpetiformis: a comparison with coeliac disease. Gut. 1996 Apr;38(4):528-30. Chartrand LJ, Russo PA, Duhaime AG, Seidman EG.  Wheat starch intolerance in patients with celiac disease. J Am Diet Assoc. 1997 Jun;97(6):612-8.


    Dr. Rodney Ford M.D.
    Celiac.com 02/27/2015 - The answer to the "oats questions" are becoming clearer.
    The long-asked question is "Can people with celiac disease or gluten sensitivity safely eat oats?" Some people are so sensitive, that even the tiniest bit of gluten makes them feel unwell. So this answer is important because people on a gluten-free diet should not restrict foods unnecessarily. There are several aspects to this question:
    1. Avenin: Oats do not naturally contain gluten ... but there is a similar protein called "avenin" found in oats that has the same properties as gluten (it is the "prolamine storage protein" of oat seeds, that helps protect the dormant seed and nourish it when it begins to grow). Fortunately, adverse reactions to this oat protein are rare. A study of 10 pertinent studies, with a total of 165 patients, found only 1 patient who had histological gut damage as a result of eating oats. This condition is now called "avenin-sensitive enteropathy" (ASE). This is documented by Garsed & Scott "Can oats be taken in a gluten-free diet? A systematic review" (Scand. J. Gastroenterol. 2007:42: 171–8.
    Clinical reports now provide strong evidence that oats very rarely cause damage to the gut mucosa in people with celiac disease. Subsequently, guidelines from many coeliac societies now reflect this new evidence. Moderate amounts of oats (half a cup of oats a day) can be consumed by most celiacs without risk of damaging intestinal villi. However, it is important to emphasise that these oats must be free of other contaminating gluten-cereals.
    What is not reported is whether some of these people experience symptoms (feel unwell) despite the healthy appearance of their gut under a microscope. These people might have an "avenin-sensitivity" similar to gluten-sensitivity without any accompanying gut damage. This question has not yet been investigated.
     
    Cross-contamination: The reason that many people apparently react to oats is not because of the avenin, but to inadvertent gluten contamination. In other words, wheat and other gluten-grains accidentally get into the oats. Traces of gluten are commonly found in packets of oats–this is from the cross-contamination of oats with other gluten-grains. This contamination can occur during any stage of the life-cycle of oat production: the planting, the harvesting, the transportation, the processing and the refining of oats. It is almost impossible to avoid such cross-contamination unless all this machinery is exclusively devoted to oats production. This requires large-scale production as is seen in the USA.
    One research group analyzed a total of 134 oats samples, comprising grains and commercial oat products collected from Europe, the United States and Canada. This study confirmed that most oats were contaminated with mixtures of wheat, barley and rye (Hernando et al. "Measurement of wheat gluten and barley hordeins in contaminated oats from Europe, the United States and Canada by Sandwich R5 ELISA". Eur J Gastroenterol Hepatol. 2008 Jun;20:545-54.)
     
    Level of gluten sensitivity: How intensely people react to gluten varies. Some people can eat moderate amounts of gluten and have no symptoms at all. Whilst many are so sensitive that even the tiniest amount upsets them. Thus, minimal cross-contamination of oats with gluten is a problem for a significant proportion of the gluten-sensitive community. It may be that people who have extreme gluten sensitivity are more likely to react to avenin. It is my observation that super-sensitive gluten reactors seldom tolerate oats. However, this subject has not been researched.
     
    Asymptomatic gluten damage: Oddly, some people can have the gut damage of celiac disease without experiencing noticeable symptoms. They have severe gut damage but are completely unaware of it. Such a diagnosis is usually discovered by screening blood test. As these people do not get any symptoms from gluten, they would not know if oats are upsetting them either! These asymptomatic celiacs need to be followed up with regular blood tests (and perhaps subsequent biopsy) to ensure that they are healing.
      Why bother with oats? The ability to use oats in your diet gives an important source of fibre as well as other important nutrients. They have a low glycemic index (GI) which makes them satisfying to eat. Also, eating oats will contribute to lower cholesterol levels. And of course, it gives you a valuable additional food to make the topping on apple-crumble, hot oat porridge on a cold morning, and a crunchy, tasty muesli.
    Some companies certify their oats to be gluten-free, which means they are free from any cross-contamination. If you are very sensitive to gluten, then you might not tolerate oats. The best thing to do is try a little and see.
     
    Do blood tests: "Get a blood test!" is my mantra. So many people go gluten-free without a blood test. So many people with celiac disease never get follow-up blood tests. It is important to get a firm diagnosis of celiac disease / gluten sensitivity. Then to get more tests a year or two later to make sure that your body is healing. One way to check out how you are tolerating oats in your body is to get regular blood test checks for gluten (IgG-gliadin) and for tissue damage (DGP/tTG)–for more details please visit me at my website.


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