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    Celiac Disease: A Look into its Pathogenesis


    Tina Turbin

    Celiac.com 07/25/2011 - Celiac disease, according to estimates, affects approximately three million Americans and as of yet, 97% haven't been correctly diagnosed. As staggering as these statistics are, celiac disease remains largely poorly understood by the medical community. It's no wonder, given its lack of research as compared with other autoimmune disorders. However, there is research being actively conducted in the U.S. and internationally in a quest to understand the pathogenesis, or the cause and development of the disease. With this information, more about celiac disease, diagnosis, prevention, and treatment can come to light.


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    According to the Canadian Celiac Association (CCA), the pathogenesis of celiac disease consists of three factors: "genetic, environment and immunologic." With regard to genetics, the CCA points out that more than 97% of celiac patients have the genetic markers HLA DQ2 and/or HLA DQ8. Celiac disease is now known to be a hereditary disease. The Canadian Celiac Association tells us that "first-degree and to a lesser extent second-degree relatives are at higher risk of having unrecognized celiac disease."

    Next, is the environmental "trigger," as Dr. Alessio Fasano, professor of pediatrics, medicine and physiology at the Center for Celiac Research at the University of Maryland School of Medicine, calls it. This is gluten, a protein found in wheat, barley, and rye. According to the Canadian Celiac Association, sometimes severe physical stressors can also trigger the immunologic reaction to gluten that is characteristic to celiac disease. Such sources of stress include pregnancy, infection, surgery, or even severe emotional stress.

    In his article, "Surprises from Celiac Disease," published in Scientific American, Dr. Fasano describes a different triad of factors involved in the pathogenesis of the disease. The first two factors are the ‘'trigger" of gluten, which sets off the immune response, and the genetic predisposition, as previously described. Fasano proposes that "other genes are likely to be involved as well, but these additional culprits may differ from person to person."

    The third factor, according to Fasano's research is an "unusually permeable gut." In fact, the author proposes that these three factors also underlie the pathogenesis of other autoimmune diseases, with of course triggers and genetic elements unique to those particular diseases. Fasano tells us that most non-celiacs have "tight junctions [that] 'glue' intestinal cells together." On the other hand, in celiac patients, these links come apart, resulting in a small intestine from which pieces of gluten leak into the tissue and stimulate a response from immune cells. Fasano's research regarding this third factor of pathogenesis offers hope of new prevention and treatment methods. He says, "Treatments that reduced leakiness could potentially ease not only celiac disease but also other autoimmune disorders involving unusually permeable intestines."

    This research into the leaky gut of celiacs can explain a question that has been perplexing researchers regarding the disease's pathogenesis: Why do some people not develop celiac disease until later in life? According to Dr. Fasano, this issue could be associated with the microbes in the digestive tract. The microbicrobial population varies among individuals and groups and even over the course of one's life.

    "Apparently they can also influence which genes in their hosts are active at any given time," he says. "Hence, a person whose immune system has managed to tolerate gluten for many years might suddenly lose tolerance if the microbiome changes in a way that causes formerly quiet susceptibility genes to become active." Should this prove true, we may be able to prevent or treat celiac disease with probiotics.

    A better understanding of the pathogenesis of celiac disease is certainly needed, but as of yet, researchers seem to be on their way to developing a full picture of what is involved in the origin and onset of the disease. By raising awareness and allocating more funding to celiac pathogenesis research, we may find ourselves with the ability to delay or even prevent the disease or with a new treatment option.

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    Thank you for taking the time to help support and educate all of us who are affected by this condition.

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  • Related Articles

    Dr. Ron Hoggan, Ed.D.
    This article appeared in the Autumn 2007 edition of Celiac.com's Scott-Free Newsletter.
    Celiac.com 03/10/2008 - Virtually every parent and every professional person who works with children wants to see them learn, grow, and achieve to the greatest extent of their potential.  The vast majority of these caregivers know that nutrition plays an enormous role in each child’s realizing their potential.  Unfortunately, that is where agreement ends.  There are almost as many perspectives on what constitutes a healthy diet as there are people on this planet.  Some claim that the healthiest diet is that of a vegetarian which almost invariably leads to a heavy reliance on grains and which is devoid of vitamin B12.  Others assert, based on cardiovascular disease being our number one killer that the best diet includes the smallest amount of fats.  They believe that fat consumption is related to blood cholesterol levels and that blood cholesterol levels are the best predictor of heart attacks.  Yet low cholesterol has been linked to increased cancer risk.  Still others argue for the health benefits conferred by a high protein diet.  They point out the importance of proteins in providing the building blocks for immune system function and the body’s maintenance and repair at the cellular level.  A small but growing faction points to the health benefits of a diet dominated by fats with little or no carbohydrate content.  Other diets target refined sugars and flours as problematic.  Added to this diversity, there is a plethora of dietary perspectives that advocate rigid proportions of fat, protein, and carbohydrates.  The proportions of each component vary according to the data that is given the most credence by the creators and advocates of each diet.  Many dietary rituals have grown up around cancer avoidance or therapy, weight loss strategies, treatments for cardiovascular disease or its avoidance, and autoimmune diseases.  Book, video tape, audio tape, menu guides, and other media sales are just a starting point.  Some advocates of specific dietary strategies are even selling special foods that comply with their recommendations.  The profit motive can be a powerful factor in creating bias.  Then there are the government sponsored healthy eating guides.  Of course, each paradigm assumes that one diet can be recommended for all people.  The USDA has recently devised recommendations that do make concessions to gender and stage-of-life (with separate recommendations for children, adults, and seniors) but even with these changes, the USDA provides a clear message advocating plenty of grains and little fat.  It is difficult to determine just how much these recommendations have been influenced by special interest lobbies.  Agricultural and food production corporations have made astronomical investments in current dietary practices and shaping new dietary trends.  Is it reasonable to expect them to be responsive to evolving research findings?  
    Those of us who have experienced the painful shock that we were ill, sometimes deathly ill, from grain proteins that come highly recommended by government food guides, have had to revise our views of healthy eating and reject such flawed guidance.  Gluten sensitivity and celiac disease often crop up in the context of what many health care professionals tout as a healthy diet.  Prior to my own diagnosis of celiac disease, I remember one physician recommending that I eat bran every morning to reverse some of the gastrointestinal problems I was having.  He would not believe that eating bran made me vomit.  There is a persistent sense that we should all know what constitutes a good diet.  Almost every one of us who have to avoid gluten knows that avoiding it is a healthy choice for us, irrespective of government or private sector recommendations for healthy eating.  We have learned not to trust these prescriptions filled with certitude and rigidity.  We have found new-found health in eating habits that are diametrically opposed to those recommendations.
     
    Thus, many of us will have a very different view of conventional dietary wisdom.  For instance, Dr. Eve Roberts, a scientist at Toronto’s Hospital for Sick Children, was quoted on Monday, September 24th in the Victoria Times Colonist as saying: “I do not want children to grow up with liver disease because we forgot to tell them how to eat” (1).  I’m sure that same attitude abounds throughout the medical profession.  Unfortunately, despite the overwhelming consensus that children should not suffer such diet-induced illnesses, there is little agreement on exactly what we should be telling children (or adults for that matter) to help them avoid fatty liver disease.  The medical literature provides research reports of several contradictions on this point. 
    In fact, contradictions abound throughout the medical literature.  So how are we to choose a healthy diet? What can we teach our children about eating well? For those of us who are gluten sensitive or have celiac disease, gluten avoidance is a given.  For our children, the answer is less clear.  They will be at greater risk of having celiac disease or gluten sensitivity, but what should we teach them about these grains? Should they avoid gluten entirely? Should they eat normally until they become ill—perhaps risking permanent neurological damage or a deadly cancer? Should they be constantly vigilant with regular blood tests, endoscopies, or IgG allergy testing?
    Many of us have been told to “just eat a balanced diet”.  It sounds appealing, but it is so vague as to provide little meaningful direction.  What is a healthy diet and how do we judge if any special interest group is more interested in health than profits? Just how much can we trust information that has a price tag attached to it? Somebody is profiting.  Can they really provide objective guidance? These questions should form part of our search for information.  There is nothing wrong with making a profit or earning a living from providing dietary advice.  However, it is important to be aware of any possible conflicts of interest.  
    For these reasons, I have developed my own strategy for determining what advice and guidance I can provide to my children and grandchildren.  I acknowledge that this approach is limited by my own biases, my finite capacity for assimilating and synthesizing information, my incomplete familiarity with nutritional research, and my own personal experiences.  On the other hand, I don’t have to worry about being directly influenced by profiteering or lobby groups diverting me from my primary purpose.
    On that basis, I have proceeded to explore my own dietary program.  I have conducted some trial-and-error experiments on myself, and I have read as extensively as my part-time avocation of dietary investigation permits.  From this, I have learned to trust my own gut.  If something doesn’t feel right in my stomach, I avoid it.  I have also learned to trust my sense of smell.  If a food does not smell appetizing to me, I don’t eat it.  I suspect that this is a tool that evolution has provided us with to determine what is and is not safe to eat.  Those without it probably stopped contributing to the human gene pool.  I have learned that IgG allergy testing is an effective tool with which I can reduce the lengthy trial-and-error process necessary for identifying the majority of allergies.  I realize that this testing has its weaknesses, but so does almost every other form of medical testing.  I have come to accept that as long as human beings are involved, we will have imperfect testing, regardless of claims to the contrary.  Finally, although I try to read critically, I read medical and scientific research reports to stay abreast of new findings and gain a better understanding of this complex field.
    The tentative conclusions I have reached, pending new information, are as follows:

    Gluten grains probably aren’t very good for people.  They are highly allergenic affecting at least 10% of the general population, and perhaps as much as 40%  of the population.  These grains also contain opioids morphine-like substances that can be highly addictive and have a deleterious effect on our ability to resist cancer.  They also contain large quantities of starch that is converted very rapidly into sugars. The evidence suggests that refined sugars and starchy foods cause many of our problems with obesity, vision problems due to growth related distortions of the eyeball, type II diabetes, and hypoglycemia.  Dairy products probably aren’t very good for anyone either.  They are also highly allergenic and contain opioids similar to those found in gluten.  Further, about two thirds of the world’s adult populations are lactose intolerant.  They don’t retain enzymes for digesting milk sugars after childhood. I think it is wise to avoid processed foods where possible.  The more they’ve been processed, the further they are from the state in which we evolved eating them. I believe it is a good idea to avoid eating soy because it has been linked to neurological diseases and other health problems that I don’t want to develop. I avoid foods to which IgG blood testing has shown to cause an immune reaction in me. I try to avoid juices, as these are mostly sugar.  Those are the things I try to avoid.  On a more positive note, there are several specific strategies that I try to follow:
    I take supplements of vitamins and minerals which evidence has shown that I either absorb poorly or have been depleted from the soils in which my food is grown. I try to eat whole fruits and vegetables. I try to eat when I am hungry—not according somebody else’s idea of appropriate mealtimes. If I am ever diagnosed with cancer, I will follow a ketogenic diet.  That is a diet that is dominated by fats, includes about 30% protein, and includes no carbohydrates.  I have tried this diet for about a month.  I can’t say that I enjoy it very much, but I’d be happy to forego the pleasure of carbohydrates if my life is at stake.
    I’m very grateful to my wife who works very hard at finding tasty treats so I don’t have to feel isolated or deprived in social situations where food is consumed.
    I’m convinced that even a little exercise is a critical feature of a well balanced diet, but that belongs in another column.
    I realize that these strategies are often impractical and I don’t pretend to live up to all of them, except for gluten and dairy avoidance.  I also suspect that I would be better off if I ate organic fruits and vegetables along with range fed meat.  I also suspect that I should avoid any genetically modified food.  We really don’t know what’s in that stuff! I haven’t reached the point yet where I am sufficiently motivated to change my diet to that extent, although I do realize that it would probably be a good idea.  I am convinced that Dr. Barry Sears is onto something when he advocates specific proportions of each food type for optimal health and performance.  Unfortunately, my diet is already complex enough that without some specific and highly motivating reason, I’m just too busy or lazy to be bothered with measuring such things.  I just let my taste buds and availability (my wife only cooks one cake at a time) determine my portion sizes.This is the balanced diet I recommend.  I sorely doubt that my children or my grandchildren follow my advice, except when they visit during mealtimes.  However I am confident that such a diet, should they choose to accept it, will not cause them to self-destruct due to dietary disease.


    Rebecca  Herman
    In 2010, the U.S. market for gluten-free products was valued at $2.6 billion.  Projected sales in this market are expected to exceed $5 billion by 2015.(1) 
    As the gluten-free product market expands, and as we continue to seek out new tools to aid us in our search for truly gluten-free products, we are in for a treat with the recent launch of Gluten Free Watchdog.  Tricia Thompson, the founder of Gluten Free Watchdog, agreed to discuss it with us.
    Can you explain what Gluten Free Watchdog is, and what is novel about it?
    Gluten Free Watchdog (www.glutenfreewatchdog.org) is a food testing site that was started to make expensive state-of-the-art gluten testing available to the gluten-free community at a fraction of the true cost. This is the first time this type of resource has been offered.
    Can you share your personal story – how you became interested in celiac disease and gluten sensitivity?
    I have been gluten free for over 27 years. In the early years, I became very frustrated by the contradictory information available on several key gluten-free issues—Are oats safe to eat? Why is wheat starch eaten by the gluten-free community in Europe? Why do some support groups say “grains” such as buckwheat, amaranth, and quinoa should be avoided? And then there was the issue of nutritional quality. Back then almost all gluten-free processed foods were made using refined rice/corn and starch. So after finishing graduate school I made a list of all the topics I wanted to research and then started writing (and writing and writing!). 
    In December 2008, the Chicago Tribune investigated three Wellshire Kids brand gluten-free products, sold exclusively at Whole Foods Market — Dinosaur Shapes Chicken Bites, Chicken Corn Dogs, and Beef Corn Dogs — and analytical results indicated that they contained gluten, ranging from 116 to 2,200 parts per million.  More recently, Paul Seeling, a North Carolina baker, was convicted of fraud relating to the packaging of wheat bread as a gluten-free product.  Have events like these influenced the Gluten Free Watchdog?
    Events such as what occurred with Wellshire Farms made me realize that some manufacturers, while well-intentioned, did not understand how consumers in the US define gluten free when they see it on a food label. It also made me realize that some manufacturers did not know how to accurately test their labeled gluten free products for gluten, and that some of them were operating under the mistaken belief that if a product is (or is made from) a naturally gluten-free grain the product does not need to be tested. We have learned a lot over the years about cross contamination, starting with the study published in the New England Journal of Medicine on gluten contamination of oats and more recently with the study on gluten contamination of naturally gluten-free grains and flours published in the Journal of the American Dietetic Association.
    Combined, these events and studies may have undermined consumer confidence in labeled gluten-free foods. Most manufacturers are doing things right. It is my hope that Gluten Free Watchdog will allow consumers to have confidence in the products they eat and feed their family.
    Over the last ten years, you have published a significant amount of research on gluten-free product labeling.  And you recently authored a chapter on gluten-free product labeling in Melinda Dennis’ and Daniel Leffler’s new book, Real Life with Celiac Disease:  Troubleshooting and Thriving Gluten Free, which was published by the American Gastroenterological Association.  How has your research influenced Gluten Free Watchdog?
    From the consumer perspective the most important thing to understand about allergen labeling is that it pertains to ingredients only—it does not pertain to allergens that may be in a product due to cross contact. Currently, Gluten Free Watchdog is only testing foods labeled gluten free. In the future, we may test foods that appear to be gluten free based on ingredients.
    The Food Allergy Labeling and Consumer Protect Act (FALCPA) does not currently require the disclosure of barley or rye; or, contamination by manufacturers on product labeling.  Can Gluten Free Watchdog help us to decipher product labeling that may be difficult to understand?

    Gluten Free Watchdog is primarily a food testing site. My other website www.glutenfreedietitian.com contains extensive information on labeling laws and ingredients.
    Under FALCPA, the Federal Food & Drug Administration (FDA) is considering a proposed government definition of the term “gluten-free” for food product labeling purposes.  Once FDA approves a final rule, will the role of Gluten Free Watchdog change?

    Possibly but it will remain primarily a food testing site. Consumers will still want to know the level of gluten at which foods are testing and will still want the added confidence that independent transparent third party testing provides.
    On your blog, Gluten Free Dietitian, you discuss R5 ELISA tests, Ridascreen 7001 and Ridascreen R7011.  What is the importance of these tests, and are these the tests that Gluten Free Watchdog is using?  Are home-test kits accurate?
    The standard sandwich R5 ELISA is one of only two commercially available ELISAs validated at the levels used for regulatory purposes and official governmental methods (the other is the Morinaga Wheat Protein ELISA). The R5 and Morinaga ELISAs also are included in the FDA’s proposed gluten-free labeling rule as possible methods for rule enforcement. The competitive R5 ELISA may be used in conjunction with the sandwich R5 ELISA when a food is highly hydrolyzed.
    Gluten Free Watchdog tests food using the standard sandwich R5 ELISA and will, if necessary, also use the competitive R5 ELISA.
    What products does Gluten Free Watchdog plan to test in the upcoming months?  Are there any products that are difficult to test; and if so, why?
    We have been and will continue to test a wide variety of products—grains, flours, breads, cereals, pastas, cookies, etc. Anyone can visit the site and browse through the products that have been tested to date. However, testing data is available only to subscribers. One of the nice features of Gluten Free Watchdog is that subscribers can request that certain products be tested.
    One of the keys to successful testing of products is getting a homogenized sample—meaning any contaminant is evenly distributed throughout the sample being tested and there are no “hot spots.” This is why we test two extractions of each “homogenized” sample at Gluten Free Watchdog—we want to make sure the sample is truly homogenized. It can sometimes be tricky to get a homogenized sample when testing raw grains in grain versus flour form.
    FALCPA does not cover foods regulated by the United States Department of Agriculture (USDA), and the Alcohol and Tobacco Tax and Trade Bureau (TTB) has yet to finalize an allergen labeling rule for distilled spirits, beer, and wine.  Under TTB’s current labeling provisions, the term “gluten-free” is considered a health claim and its use is prohibited.  Are USDA and TTB adequately protecting consumers?  If not, does Gluten Free Watchdog plan to test any products regulated by either?
    Neither the TTB nor the USDA have mandatory allergen labeling and it will be interesting to see how they proceed with gluten-free labeling once the FDA’s gluten-free labeling law is in place. I have been told by representatives of the USDA that they will adopt the FDA’s gluten-free labeling law rather than develop their own.
    Gluten Free Watchdog will test USDA-regulated foods that are labeled gluten free. As mentioned earlier, we may start testing foods that appear to be gluten free based on ingredients. When we do, we would be happy to test beverages regulated by the TTB.
    Is Gluten Free Watchdog affiliated with any companies that sell or market gluten-free products?
    Nope! That is why we really need the support of gluten-free consumers!! It is my hope that members of the gluten-free community will see the value in having this type of resource available and will be willing to contribute a relatively small amount in exchange for access to expensive testing and input on what is tested—similar to a co-op.
    Source:

    Gluten-Free Foods and Beverages in the U.S., 3rd Edition.  Packaged Facts, February 2011.

    Jefferson Adams
    Celiac.com 09/07/2012 - Many people with celiac disease will tell you that getting a proper diagnosis is just part of the battle. Maintaining a strict gluten-free diet, and getting adequate medical follow-up care can be nearly as challenging as getting a proper diagnosis.
    A group of researchers, led by Joseph A. Murray, MD, AGAF, of Mayo Clinic, confirms that assessment in a new study. The study appears in Clinical Gastroenterology and Hepatology, and shows that follow-up care for patients with celiac disease is often poor and inconsistent.
    For their study, researchers collected data on 122 patients diagnosed with celiac disease between 1996 and 2006 in Olmsted County, MN. The patients were 70 percent women, and averaged 42 years of age.
    The researchers then calculated the rates at which patients were given follow-up exams from six months to five years after celiac disease diagnosis.
    Of the 113 patients the study followed for more than four years, only 35 percent received follow-up analyses that met AGA guidelines. The other patients did not receive medical follow-up that met "even the most lax interpretation of current guidelines,” said Dr. Murray.
    The researchers used the Kaplan-Meier method to estimate event rates at 1 and 5 years. They classified patients according to categories of follow-up procedures recommended by the American Gastroenterological Association (AGA).
    The study shows that even with widespread circulation of follow-up recommendations, plenty of patients are not getting proper follow-up for celiac disease.
    According to Dr. Murray, gastroenterologists with the expertise in celiac disease need to encourage active follow-up of celiac patients and improve their overall quality of medical care.
    Basically, says Dr. Murray, celiac disease "should not be different from other chronic conditions for which medical follow up is a given such as liver disease, inflammatory bowel disease or even gastroesophageal reflux disease."
    Anecdotally, many patients with celiac disease feel that they must manage celiac disease on their own,” Murray adds, pointing out that it is important for doctors and patients to understand the need for proper medical follow-up of celiac disease.
    The authors note that, since gastroenterologists are leading the way in the detection of celiac disease, and since it is a chronic condition, with possible long-term complications, improved communication between gastroenterologists and patients can help to ensure that patients get important follow-up care, and thus improve outcomes in celiac disease.
    What are your thoughts? Do you feel that you've gotten adequate follow-up care for your celiac disease? Share your comments below.
    Source:
    Clinical Gastroenterology and Hepatology

    Jefferson Adams
    Celiac.com 12/19/2014 - News that the Arizona Diamondbacks have traded starting pitcher Wade Miley to the Boston Redsox has been met with rumors that Miley’s trade was fueled, at least partly, by his refusal to adopt a gluten-free diet.
    So what’s the deal? Did gobbling gluten cost Wade Miley his job with the Diamondbacks?
    For his part, Miley, who was picked up by Boston last week, says he had butted heads this year with the Diamondbacks organization about not being gluten-free.
    "After a while, they left me alone," he said. "But it was always that elephant in the room."
    Without getting into specifics, Miley said that a gluten-free diet “might work for some people, but I didn't feel like it worked for me.”
    So, according to Miley, his refusal to go gluten-free was an issue. But, was it an issue that got him traded? Diamondbacks GM Dave Stewart says that Miley’s diet was “never once discussed” by the team in the run up to the trade.
    So, we may never know for sure just how much Miley’s refusal to give up gluten, or his attitudes about it, impacted his trade to Boston.
    What many may wonder is whether right-handers Rubby De La Rosa and Allen Webst, whom the Diamondbacks acquired in the trade, will be giving up their taste for those famously delicious toasted Boston-style subs when they come to Phoenix. Will they be going gluten-free?
    What do you think? Should a sports team be able to make its players eat a certain way? Is it healthier for athletes to eat gluten-free? 

  • Recent Articles

    Jefferson Adams
    Celiac.com 06/16/2018 - Summer is the time for chips and salsa. This fresh salsa recipe relies on cabbage, yes, cabbage, as a secret ingredient. The cabbage brings a delicious flavor and helps the salsa hold together nicely for scooping with your favorite chips. The result is a fresh, tasty salsa that goes great with guacamole.
    Ingredients:
    3 cups ripe fresh tomatoes, diced 1 cup shredded green cabbage ½ cup diced yellow onion ¼ cup chopped fresh cilantro 1 jalapeno, seeded 1 Serrano pepper, seeded 2 tablespoons lemon juice 2 tablespoons red wine vinegar 2 garlic cloves, minced salt to taste black pepper, to taste Directions:
    Purée all ingredients together in a blender.
    Cover and refrigerate for at least 1 hour. 
    Adjust seasoning with salt and pepper, as desired. 
    Serve is a bowl with tortilla chips and guacamole.

    Dr. Ron Hoggan, Ed.D.
    Celiac.com 06/15/2018 - There seems to be widespread agreement in the published medical research reports that stuttering is driven by abnormalities in the brain. Sometimes these are the result of brain injuries resulting from a stroke. Other types of brain injuries can also result in stuttering. Patients with Parkinson’s disease who were treated with stimulation of the subthalamic nucleus, an area of the brain that regulates some motor functions, experienced a return or worsening of stuttering that improved when the stimulation was turned off (1). Similarly, stroke has also been reported in association with acquired stuttering (2). While there are some reports of psychological mechanisms underlying stuttering, a majority of reports seem to favor altered brain morphology and/or function as the root of stuttering (3). Reports of structural differences between the brain hemispheres that are absent in those who do not stutter are also common (4). About 5% of children stutter, beginning sometime around age 3, during the phase of speech acquisition. However, about 75% of these cases resolve without intervention, before reaching their teens (5). Some cases of aphasia, a loss of speech production or understanding, have been reported in association with damage or changes to one or more of the language centers of the brain (6). Stuttering may sometimes arise from changes or damage to these same language centers (7). Thus, many stutterers have abnormalities in the same regions of the brain similar to those seen in aphasia.
    So how, you may ask, is all this related to gluten? As a starting point, one report from the medical literature identifies a patient who developed aphasia after admission for severe diarrhea. By the time celiac disease was diagnosed, he had completely lost his faculty of speech. However, his speech and normal bowel function gradually returned after beginning a gluten free diet (8). This finding was so controversial at the time of publication (1988) that the authors chose to remain anonymous. Nonetheless, it is a valuable clue that suggests gluten as a factor in compromised speech production. At about the same time (late 1980’s) reports of connections between untreated celiac disease and seizures/epilepsy were emerging in the medical literature (9).
    With the advent of the Internet a whole new field of anecdotal information was emerging, connecting a variety of neurological symptoms to celiac disease. While many medical practitioners and researchers were casting aspersions on these assertions, a select few chose to explore such claims using scientific research designs and methods. While connections between stuttering and gluten consumption seem to have been overlooked by the medical research community, there is a rich literature on the Internet that cries out for more structured investigation of this connection. Conversely, perhaps a publication bias of the peer review process excludes work that explores this connection.
    Whatever the reason that stuttering has not been reported in the medical literature in association with gluten ingestion, a number of personal disclosures and comments suggesting a connection between gluten and stuttering can be found on the Internet. Abid Hussain, in an article about food allergy and stuttering said: “The most common food allergy prevalent in stutterers is that of gluten which has been found to aggravate the stutter” (10). Similarly, Craig Forsythe posted an article that includes five cases of self-reporting individuals who believe that their stuttering is or was connected to gluten, one of whom also experiences stuttering from foods containing yeast (11). The same site contains one report of a stutterer who has had no relief despite following a gluten free diet for 20 years (11). Another stutterer, Jay88, reports the complete disappearance of her/his stammer on a gluten free diet (12). Doubtless there are many more such anecdotes to be found on the Internet* but we have to question them, exercising more skepticism than we might when reading similar claims in a peer reviewed scientific or medical journal.
    There are many reports in such journals connecting brain and neurological ailments with gluten, so it is not much of a stretch, on that basis alone, to suspect that stuttering may be a symptom of the gluten syndrome. Rodney Ford has even characterized celiac disease as an ailment that may begin through gluten-induced neurological damage (13) and Marios Hadjivassiliou and his group of neurologists and neurological investigators have devoted considerable time and effort to research that reveals gluten as an important factor in a majority of neurological diseases of unknown origin (14) which, as I have pointed out previously, includes most neurological ailments.
    My own experience with stuttering is limited. I stuttered as a child when I became nervous, upset, or self-conscious. Although I have been gluten free for many years, I haven’t noticed any impact on my inclination to stutter when upset. I don’t know if they are related, but I have also had challenges with speaking when distressed and I have noticed a substantial improvement in this area since removing gluten from my diet. Nonetheless, I have long wondered if there is a connection between gluten consumption and stuttering. Having done the research for this article, I would now encourage stutterers to try a gluten free diet for six months to see if it will reduce or eliminate their stutter. Meanwhile, I hope that some investigator out there will research this matter, publish her findings, and start the ball rolling toward getting some definitive answers to this question.
    Sources:
    1. Toft M, Dietrichs E. Aggravated stuttering following subthalamic deep brain stimulation in Parkinson’s disease--two cases. BMC Neurol. 2011 Apr 8;11:44.
    2. Tani T, Sakai Y. Stuttering after right cerebellar infarction: a case study. J Fluency Disord. 2010 Jun;35(2):141-5. Epub 2010 Mar 15.
    3. Lundgren K, Helm-Estabrooks N, Klein R. Stuttering Following Acquired Brain Damage: A Review of the Literature. J Neurolinguistics. 2010 Sep 1;23(5):447-454.
    4. Jäncke L, Hänggi J, Steinmetz H. Morphological brain differences between adult stutterers and non-stutterers. BMC Neurol. 2004 Dec 10;4(1):23.
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    Jefferson Adams
    Celiac.com 06/14/2018 - Refractory celiac disease type II (RCDII) is a rare complication of celiac disease that has high death rates. To diagnose RCDII, doctors identify a clonal population of phenotypically aberrant intraepithelial lymphocytes (IELs). 
    However, researchers really don’t have much data regarding the frequency and significance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. Such data could provide useful comparison information for patients with RCDII, among other things.
    To that end, a research team recently set out to try to get some information about the frequency and importance of clonal T cell receptor (TCR) gene rearrangements (TCR-GRs) in small bowel (SB) biopsies of patients without RCDII. The research team included Shafinaz Hussein, Tatyana Gindin, Stephen M Lagana, Carolina Arguelles-Grande, Suneeta Krishnareddy, Bachir Alobeid, Suzanne K Lewis, Mahesh M Mansukhani, Peter H R Green, and Govind Bhagat.
    They are variously affiliated with the Department of Pathology and Cell Biology, and the Department of Medicine at the Celiac Disease Center, New York Presbyterian Hospital/Columbia University Medical Center, New York, USA. Their team analyzed results of TCR-GR analyses performed on SB biopsies at our institution over a 3-year period, which were obtained from eight active celiac disease, 172 celiac disease on gluten-free diet, 33 RCDI, and three RCDII patients and 14 patients without celiac disease. 
    Clonal TCR-GRs are not infrequent in cases lacking features of RCDII, while PCPs are frequent in all disease phases. TCR-GR results should be assessed in conjunction with immunophenotypic, histological and clinical findings for appropriate diagnosis and classification of RCD.
    The team divided the TCR-GR patterns into clonal, polyclonal and prominent clonal peaks (PCPs), and correlated these patterns with clinical and pathological features. In all, they detected clonal TCR-GR products in biopsies from 67% of patients with RCDII, 17% of patients with RCDI and 6% of patients with gluten-free diet. They found PCPs in all disease phases, but saw no significant difference in the TCR-GR patterns between the non-RCDII disease categories (p=0.39). 
    They also noted a higher frequency of surface CD3(−) IELs in cases with clonal TCR-GR, but the PCP pattern showed no associations with any clinical or pathological feature. 
    Repeat biopsy showed that the clonal or PCP pattern persisted for up to 2 years with no evidence of RCDII. The study indicates that better understanding of clonal T cell receptor gene rearrangements may help researchers improve refractory celiac diagnosis. 
    Source:
    Journal of Clinical Pathologyhttp://dx.doi.org/10.1136/jclinpath-2018-205023

    Jefferson Adams
    Celiac.com 06/13/2018 - There have been numerous reports that olmesartan, aka Benicar, seems to trigger sprue‐like enteropathy in many patients, but so far, studies have produced mixed results, and there really hasn’t been a rigorous study of the issue. A team of researchers recently set out to assess whether olmesartan is associated with a higher rate of enteropathy compared with other angiotensin II receptor blockers (ARBs).
    The research team included Y.‐H. Dong; Y. Jin; TN Tsacogianis; M He; PH Hsieh; and JJ Gagne. They are variously affiliated with the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School in Boston, MA, USA; the Faculty of Pharmacy, School of Pharmaceutical Science at National Yang‐Ming University in Taipei, Taiwan; and the Department of Hepato‐Gastroenterology, Chi Mei Medical Center in Tainan, Taiwan.
    To get solid data on the issue, the team conducted a cohort study among ARB initiators in 5 US claims databases covering numerous health insurers. They used Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy‐related outcomes, including celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy. In all, they found nearly two million eligible patients. 
    They then assessed those patients and compared the results for olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. They found unadjusted incidence rates of 0.82, 1.41, 1.66 and 29.20 per 1,000 person‐years for celiac disease, malabsorption, concomitant diagnoses of diarrhea and weight loss, and non‐infectious enteropathy respectively. 
    After PS matching comparing olmesartan to other ARBs, hazard ratios were 1.21 (95% CI, 1.05‐1.40), 1.00 (95% CI, 0.88‐1.13), 1.22 (95% CI, 1.10‐1.36) and 1.04 (95% CI, 1.01‐1.07) for each outcome. Patients aged 65 years and older showed greater hazard ratios for celiac disease, as did patients receiving treatment for more than 1 year, and patients receiving higher cumulative olmesartan doses.
    This is the first comprehensive multi‐database study to document a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, though absolute rates were low for both groups.
    Source:
    Alimentary Pharmacology & Therapeutics

    Jefferson Adams
    Celiac.com 06/12/2018 - A life-long gluten-free diet is the only proven treatment for celiac disease. However, current methods for assessing gluten-free diet compliance are lack the sensitivity to detect occasional dietary transgressions that may cause gut mucosal damage. So, basically, there’s currently no good way to tell if celiac patients are suffering gut damage from low-level gluten contamination.
    A team of researchers recently set out to develop a method to determine gluten intake and monitor gluten-free dietary compliance in patients with celiac disease, and to determine its correlation with mucosal damage. The research team included ML Moreno, Á Cebolla, A Muñoz-Suano, C Carrillo-Carrion, I Comino, Á Pizarro, F León, A Rodríguez-Herrera, and C Sousa. They are variously affiliated with Facultad de Farmacia, Departamento de Microbiología y Parasitología, Universidad de Sevilla, Sevilla, Spain; Biomedal S.L., Sevilla, Spain; Unidad Clínica de Aparato Digestivo, Hospital Universitario Virgen del Rocío, Sevilla, Spain; Celimmune, Bethesda, Maryland, USA; and the Unidad de Gastroenterología y Nutrición, Instituto Hispalense de Pediatría, Sevilla, Spain.
    For their study, the team collected urine samples from 76 healthy subjects and 58 patients with celiac disease subjected to different gluten dietary conditions. To quantify gluten immunogenic peptides in solid-phase extracted urines, the team used a lateral flow test (LFT) with the highly sensitive and specific G12 monoclonal antibody for the most dominant GIPs and an LFT reader. 
    They detected GIPs in concentrated urines from healthy individuals previously subjected to gluten-free diet as early as 4-6 h after single gluten intake, and for 1-2 days afterward. The urine test showed gluten ingestion in about 50% of patients. Biopsy analysis showed that nearly 9 out of 10 celiac patients with no villous atrophy had no detectable GIP in urine, while all patients with quantifiable GIP in urine showed signs of gut damage.
    The ability to use GIP in urine to reveal gluten consumption will likely help lead to new and non-invasive methods for monitoring gluten-free diet compliance. The test is sensitive, specific and simple enough for clinical monitoring of celiac patients, as well as for basic and clinical research applications including drug development.
    Source:
    Gut. 2017 Feb;66(2):250-257.  doi: 10.1136/gutjnl-2015-310148.