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    What Happens to Kids with Potential Celiac Disease Who Eat Gluten?


    Jefferson Adams
    Image Caption: Photo: CC--Chad Miller

    Celiac.com 09/03/2014 - What’s potential celiac disease, and what happens to kids who have it and continue to eat a gluten-containing diet?


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    Researchers define potential celiac disease as the presence of serum anti-tissue-transglutaminase (anti-TG2) antibodies with normal duodenal mucosa. That is, a positive blood screen, but no intestinal damage. However, not much is known about potential celiac disease because people who have it often show no obvious symptoms. Patients with potential celiac disease present some challenges for doctors trying to determine how likely it is that these patients will develop villous atrophy, the gut damage common in celiac disease patients exposed to gluten.

    Photo: CC--Chad MillerA research team conducted a prospective longitudinal cohort study to follow patients with potential celiac disease up to 9 years, and explore the risk factors tied to mucosal damage. The research team included Renata Auricchio MD, PhD, Antonella Tosco MD, Emanuela Piccolo MD, Martina Galatola PhD, Valentina Izzo PhD, Mariantonia Maglio PhD, Francesco Paparo PhD, Riccardo Troncone MD, PhD, and Luigi Greco MD, PhD. They are affiliated with the Department of Medical Translational Science, European Laboratory for the Investigation of Food Induced Disease (ELFID), University Federico II, Naples, Italy.

    For their study, the team found two hundred and ten asymptomatic children with potential celiac disease. They kept 175 of them on a gluten-containing diet. To evaluate histological, immuno-histochemical, and anti-TG2 status, they checked blood antibody levels and clinical symptoms every 6 months, and took a small bowel biopsy every two years. They also genotyped all patients for HLA and non-HLA celiac-associated genes.

    Forty-three percent of patients showed persistently elevated anti-TG2 levels, 20% became negative during follow-up, and 37% showed variations in anti-TG2 course, with many patients testing at zero anti-TG2.

    After three years of follow-up, 86% of study patients continued to have potential celiac disease. After 6 and 9 years, respectively, 73% and 67% of study patients still had normal duodenal structure.

    Individuals prone to develop mucosal damage during the test period were predominantly male, had slight mucosal inflammation at study’s start, and fit a peculiar genetic profile.

    Nine years after follow-up, a large number of patients with asymptomatic potential celiac disease showed reduced antibody production, many even showing zero production, and many of these, with persistently positive anti-TG2, showed no mucosal damage.

    Given the results of this study, and noting that the celiac population is in fact made up of numerous individuals with diverse genetic and phenotypic makeup, the researchers are advising doctors to be cautious in prescribing a strict lifelong gluten-free diet for asymptomatic individuals with potential celiac disease.

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    Guest Richard Duvall

    Posted

    I'm wondering if the phrase "researchers are advising doctors to be cautious in prescribing a strict lifelong gluten-free diet for asymptomatic individuals with potential celiac disease" means they should be cautious by prescribing a GFD although it may make no difference, or does it mean doctors should be cautious before prescribing a diet that will be a lifelong burden to someone who may not need it?

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    The next question is: What happens to those same people at age 20, age 30, age 40, etc. Are they more or less likely to develop full-blown celiac disease?

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    Guest Michael

    Posted

    The doctors who recommend these children continue to eat gluten are woefully ignorant and dangerous to society, because they have no clue that all organs will eventually become targets of the immune systems of those with anti tTG, as will those of their children and their children. The central nervous systems and endocrine systems are more vulnerable and more often the target of the gluten sensitive immune systems than the intestinal mucosa.

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    Guest celiacMom

    Posted

    Seems like good research, hope they do more like this to keep knowledge moving forward.

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    Too bad this is not written in everyday English that the average layman can understand. Those of us with children who have celiac would like to learn something helpful to contribute to our children's good health.

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    Guest Jefferson

    Posted

    Too bad this is not written in everyday English that the average layman can understand. Those of us with children who have celiac would like to learn something helpful to contribute to our children's good health.

    If your child actually has celiac disease, then this article is not relevant to their health or medical condition. As for your level of comprehension, other "laymen" readers and those making comments don't seem to have the same problem, but keep reading such articles, and perhaps you will learn to understand them better.

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    The doctors who recommend these children continue to eat gluten are woefully ignorant and dangerous to society, because they have no clue that all organs will eventually become targets of the immune systems of those with anti tTG, as will those of their children and their children. The central nervous systems and endocrine systems are more vulnerable and more often the target of the gluten sensitive immune systems than the intestinal mucosa.

    Couldn't agree more!

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    Guest ginny

    Posted

    The doctors who recommend these children continue to eat gluten are woefully ignorant and dangerous to society, because they have no clue that all organs will eventually become targets of the immune systems of those with anti tTG, as will those of their children and their children. The central nervous systems and endocrine systems are more vulnerable and more often the target of the gluten sensitive immune systems than the intestinal mucosa.

    I have celiac disease and hardly ever ate gluten before finding out and had a lot of organ issues !!!

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  • About Me

    Jefferson Adams is a freelance writer living in San Francisco. He has covered Health News for Examiner.com, and provided health and medical content for Sharecare.com. His work has appeared in Antioch Review, Blue Mesa Review, CALIBAN, Hayden's Ferry Review, Huffington Post, the Mississippi Review, and Slate, among others.

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    Roy Jamron
    This article originally appeared in the Spring 2004 edition of Celiac.com's Scott-Free Newsletter.
    Celiac.com 05/10/2004 - Identical twins enter life from the same womb sharing the same genetic code, the same family, the same home, largely experiencing the same environment as they develop from infancy through childhood and mature into adults. When celiac disease strikes one identical twin, the odds are the other twin also has celiac disease. Twin studies lead to the conclusion that celiac disease is strongly linked to genetic factors. Yet one identical twin may develop celiac disease while the other twin may remain completely free of celiac disease for decades if not for a lifetime.
    One study looked at 20 pairs of identical twins and 27 pairs of fraternal twins where at least one twin of the pair was known to have celiac disease. In 75% of the pairs of identical twins, both twins had celiac disease. In contrast, in only 11% of the pairs of fraternal twins did both twins have celiac disease. However, in 25% of the 20 identical twin pairs studied, one twin of the pair did not have celiac disease1. In another study which followed 5 pairs of female identical twins for 11-23 years (at least one twin of the pair having celiac disease or dermatitis herpetiformis), it was found that two of the twins who began the study with neither celiac disease or dermatitis herpetiformis remained free of the disease throughout the study2. In other words, something beyond genetics, some environmental factor, seems to be responsible for the onset of celiac disease. Exactly what is it that makes one twin intolerant to gluten and not the other?
    Looking for Answers
    To find an answer, one might start by asking when do signs of an intolerance to gluten first begin to emerge? A recent study in the UK looked at a screened sample of 5,470 children aged 7 years old and found 54 who tested positive for both tTG antibodies and IgA-EMA (tissue transglutaminase and antiendomysial antibodies) indicating celiac disease is likely present. This 1% prevalence in children is comparable to the 1% prevalence of celiac disease in adults in the UK. Since the prevalence of celiac disease is not greater in adults, this suggests that the onset of celiac disease begins in early childhood, even in cases where celiac disease is not diagnosed until later in adulthood. The authors of this study concluded, “The search for the trigger resulting in the breakdown of immune tolerance to gluten therefore needs to focus on infancy and intrauterine life3.”
    Breast-Feeding
    Breast-feeding has long been thought to delay or reduce the risk of developing celiac disease in children. This effect has been attributed to a number of potentially protective milk components and antibodies passed from the mother. Studies relying on questionnaires have found that the onset of celiac disease in children is significantly delayed if gluten is introduced into the diet while the child is still being breast-fed4-7. The effect of epidermal growth factor (EGF), a component of breast milk, was studied in newborn rats. Interferon-gamma and gliadin, a gluten protein, were administered to rat pups to induce gluten enteropathy. Celiac disease-like villus atrophy was found in rat pups fed an artificial milk diet without EGF but not in breast-fed pups or pups supplemented with EGF8. Recent research shows that breast milk also passes bacterial flora from mother to newborn9. Growth factors found in human milk have been shown to aid in establishing predominant species of commensal bacteria in the gut of breast-fed infants10. The makeup of microflora which colonize the gut in early infancy is dependant on many factors, including whether babies are bottle-fed or exclusively breast-fed, whether or not delivered by caesarean section, on treatment in neonatal intensive care units, hygienic conditions, and antimicrobial procedures. Initially, it is the maternal microflora that is the source of bacteria for the newborn gut. A diet of breast milk induces the development of a flora rich in Bifidobacterium in full-term infants11. The possibility that these microflora play critical symbiotic roles in the development of the intestine and its immunological functions has not yet been considered as a factor in the onset of celiac disease.
    The Beneficial Roles of Gut Bacteria
    Over 500 species of bacteria may be present in the human gut in concentrations of between 100 billion to 1 trillion microbes per gram adding up to about 95% of the total number of cells in the human body12,13. For many years it has been known that gut bacteria play an important and beneficial role in one’s health. Extraordinary new findings on how commensal microflora participate in early gut development and in the development of the immune system have been uncovered by recent research. Here is sampling of some of these discoveries:
    A study of 64 healthy formula and breast-fed infants, aged 0-6 months, examined fecal samples for intestinal colonization of Bacteriodes fragilis, Bifidobacterium-like, and Lactobacillus-like bacteria, and compared these results with counts of IgA, IgM, and IgG antibody-secreting cells in blood fluids drawn from the infants. The result was that infants colonized with B. fragilis at one month of age had significantly higher counts of IgA- and IgM-secreting cells at the age of two months than infants not colonized with B. fragilis. It was concluded that colonization timing and the type of bacteria colonizing the gut of newborns may influence the maturation of the naive immune system14.
    Bacteriodes thetaiotaomicron, a species abundant in the guts of humans and mice, has been the focus of much research, chosen because of its predominance in the microflora and ability to be genetically manipulated. Studies of this microbe introduced into the developing guts of gnotobiotic (germ-free) laboratory mice have found B. thetaiotaomicron seems to communicate with host cells in the intestine, altering and influencing gut development and function.
    One study has shown gene activity in the host is affected by B. thetaiotaomicron colonization. Using sophisticated DNA microarray devices, a comparison of gene expression of some 25,000 mouse genes was made between germ-free and B. thetaiotaomicron colonized mice. The activity of 118 genes was found to be increased or reduced by colonization. These genes are involved in several important intestinal functions, including nutrient absorption, intestinal permeability, toxin neutralization, intestinal blood vessel development, and postnatal gut maturation suggesting that these functions should be examined further in future studies15.
    An influence on fructose production in the gut by B. thetaiotaomicron was the first finding uncovered by researchers. Pre-weaned mice produce fructose sugar on the surface of cells lining the intestine providing a food source helping to establish commensal bacteria. B. thetaiotaomicron colonizing the gut of germ-free mice causes intestinal cells to continue fructose production after weaning. If B. thetaiotaomicron is not present after weaning, fructose synthesis stops. B. thetaiotaomicron actually senses when its supply of fructose is low and instructs the host to produce more fructose in response16.
    Gene activity findings led researchers to look at the development of the intricate network of intestinal blood vessels in mice raised germ-free and in mice raised colonized with B. thetaiotaomicron or normal gut flora. When the mice reached adulthood, capillary development in the intestines was examined. Capillary development in mice colonized with B. thetaiotaomicron or normal flora was normal and complex, but capillary development in the germ-free mice was immature and arrested. Further, it was, found for blood vessel development to occur, these microbes must interact with Paneth cells (epithelial cells located at the base of the “crypts” in the small intestine)17.
    The relationship of B. thetaiotaomicron with Paneth cells was further studied. It was discovered that Paneth cells produce a protein called angiogenin 4 or Ang4 and that Paneth cells are induced to express Ang4 by B. thetaiotaomicron. Ang4 and other angiogenins were found to exhibit bactericidal and fungicidal activities against certain known pathogens. It appears that B. thetaiotaomicron and other commensal microbes, which are themselves resistant to Ang4, take part in shaping the microbial ecology of the gut and innate immunity18.
    Another study found a relationship between commensal bacteria and the development of gut-associated lymphoid tissue (GALT) in rabbits. GALT consists of lymphocytes and organized tissues called Peyer’s patches and mesenteric lymph nodes (MLNs) located within the intestinal mucosa, which are involved in the induction of immunity and tolerance. During the first few months after birth, newborn animals and humans rely on antibodies passed maternally to fend off infections until the immune system can mature. After those first few months, a diversification of antibody repertoire normally takes place within the GALT. When, shortly after birth, the appendices of rabbits are tied-off and isolated to prevent colonization by microflora, GALT development within the appendices is arrested. Rabbit pups delivered sterilely, isolated and hand-reared on a sterile diet exhibited underdeveloped GALT and antibody repertoires. In further experimentation, a number of different bacteria species were introduced into surgically-rendered, germ-free appendices of rabbits. No bacteria species alone promoted GALT development. However, the combination of Bacteroides fragilis and Bacillus subtilis consistently resulted in the development of GALT and antibody repertoire. The conclusion is that specific combinations of microflora are required for GALT development19,20.
    In other research, the composition of commensal flora in rats was shown to alter intestinal permeability. Colonization with Escherichia coli, Klebsiella pneumoniae, and Streptococcus viridans significantly increased colonic wall permeability while colonization with the common probiotic strain, Lactobacillus brevis, significantly reduced permeability of the colon wall. Bacteroides fragilis induced only a slight permeability reduction21.
    Gut pathogens in combination with stimulation by cytokines such as TNF-alpha (tumor necrosis factor) can cause cells of the intestinal epithelium to respond by releasing proinflammatory cytokines like interleukin-8 (IL-8). A study found that probiotic strains, Bifidobacterium longum and Lactobacillus bulgaricus, can suppress IL-8 secretion in intestinal epithelia when stimulated by proinflammatory cytokines. Hence, some probiotic strains of bacteria may be able to down-regulate inflammation in the gut22.
    Other beneficial functions of microflora include the fermentation and removal of non-digestible dietary residue and the mucus residue produced by the epithelia; the derivation of energy as short-chain fatty acids by fermentation of carbohydrates in the colon; the production of vitamins, particularly those of the B group and vitamin K; the absorption of minerals and ions including calcium, magnesium and iron; and the formation of a protective functional barrier against pathogens23,24.
    A Role for Bacteria in Celiac Disease?
    As can been seen, commensal microflora play a myriad of complex, diverse and important roles in normal health and development. Much remains to be investigated, and new roles and functions microflora play are waiting to be discovered. The possibility that commensal bacteria are involved in the pathogenesis of celiac disease cannot be overlooked. Certainly, differences in the mix of microflora could account for why one identical twin may develop celiac disease while the other does not. Could the mix of commensal bacteria in newborn infants set the stage for the development of celiac disease? Could the onset of celiac disease be triggered by an event such as illness, use of antibiotics, stress, or pregnancy which alters the mix of microflora opening the door to a pathogenic interaction with gluten? One recent study has already found an association between antibiotic use and the development of Crohn’s disease25.
    Over the course of the last few years, much new understanding of the pathogenesis of celiac disease has come to light, but a fundamental question remains unanswered: Why does the immune system fail to tolerate gluten in some people? A possible mechanism involving one or more unidentified species of commensal bacteria possibly explaining why tolerance to gluten fails will be proposed and discussed here.
    Tolerance and Immunity
    The subject of tolerance and immunity is involved and complex, and science remains far from fully comprehending its workings. At heart, is how the immune system decides to react when an antigen is first presented to a naive T cell. The response of the immune system to an antigen is mediated and regulated by cell secretions of numerous proteins called “cytokines” sensed by a multitude of receptors on the various specialized cells of the immune system. Structural components of pathogens are also sensed by immune cell receptors called “Toll-like receptors”. Antigens may be any substance foreign to the body and may or may not actually be harmful. They could be components of food, or could be components of either friendly or pathogenic organisms.
    In celiac disease, the antigens are those gluten peptides which survive the process of digestion. In the current understanding of celiac disease, these peptides are transported across the mucosal epithelium as polypeptides. In mainly the subepithelial region, gluten peptides undergo a process called deamidation by an enzyme called tissue transglutaminase (tTG). A peptide is a chain of amino acids. Deamidation is a process that converts glutamine amino acid components of a gluten peptide into glutamic acid components. In the lamina propria region of the intestines, deamidated gluten peptides are taken up by antigen presenting cells called dendritic cells and presented by HLA-DQ2 or -DQ8 molecules on the surface of dendritic cells to receptors of gluten-sensitive naive CD4+ T cells (Note celiac disease here refers to a “cluster of differentiation” number, a numbering system for the cell-surface molecules which identify T cell type). Activated CD4+ T cells then differentiate and proliferate. Some T cells interact with B cells which, in turn, then differentiate into plasma cells producing antigliadin, antiendomysial and anti-tTG antibodies. Other T cells become natural killer or cytotoxic T cells, secreting cytokines which cause inflammation and damage to the enterocytes in the epithelium. Connective tissue cells called “fibroblasts” increase their output of matrix metalloproteinase enzymes which may play an active role in villus atrophy. Intraepithelial lymphocytes also increase, but their role is not clear26-29.
    Human leukocyte antigen (HLA) genes encode the class II molecules DQ2 and DQ8, the key genetic risk factors in celiac disease. The HLA system is the human version of the major histocompatibility complex (MHC). HLA class II molecules are expressed on the surface of antigen presenting cells such as dendritic cells. Virtually all celiac disease patients carry DQ2 or DQ8, but carrying DQ2 or DQ8 alone does not confer celiac disease. DQ2 and DQ8 molecules may be encoded by several different haplotypes. Haplotypes are combinations of alternative genes for the same trait (alleles) occupying different locations on a chromosome which tend to be inherited as a group. These DQ2 and DQ8 molecules play a central role in the pathogenesis of celiac disease. The function of HLA class II molecules is to bind peptide antigens and present them to CD4+ T-cell receptors. The pattern of amino acids in the makeup of the chain that forms the peptide antigen is called an epitope, and that pattern is crucial to the binding between HLA molecule and peptide. It is the misfortune of celiac disease patients that epitopes of deamidated gluten peptides just happen to match up and firmly anchor into the binding grooves of DQ2 and DQ8 molecules. This strong binding results in the activation of CD4+ T cells and the subsequent processes which damage the intestinal epithelia. But why is it that CD4+ T cells are not activated in everyone who possesses the appropriate HLA-DQ2 and -DQ8 haplotypes? The question arises again. Why is one identical twin tolerant to gluten and not the other?26-30
    Dendritic Cells
    Whether an outcome of tolerance or intolerance results when a dendritic cell presents an antigen to a naive T cell depends on many factors. A dendritic cell is a special type of white blood cell (leukocyte) which circulates throughout the body looking to acquire antigens. Dendritic cells engulf and internalize antigens through a process called endocytosis. In receptor-mediated endocytosis, dendritic cells express a variety of surface receptors to capture protein antigens. In macropinocytosis, dendritic cells surround and “drink up” soluble antigens. In phagocytosis, dendritic cells engulf pathogenic bacteria, viruses, fungi, dead or infected cells, or their products. After digestion and processing, the antigens are bound to HLA (or MHC) molecules and expressed on the surface of dendritic cells for presentation to T cells. Antigen presentation occurs after dendritic cells migrate to the lymph nodes which are rich with T cells. T cell activation also requires secondary stimulation by costimulatory molecules expressed on the dendritic cell surface. Dendritic cells have three stages in their life cycle: Precursor, immature and mature. Precursor dendritic cells arise from the bone marrow. Subsets of precursor dendritic cells have been identified that grow and differ with regard to observable characteristics (phenotype), function and anatomical location. Studies have linked dendritic cell subsets with particular functions such as T cell differentiation or tolerance induction. Immature dendritic cells spread throughout tissues seeking antigens. Dendritic cells enter the mature stage when they reach the lymph nodes after antigen capture and having become primed and ready to activate T cells with antigens and costimulatory molecules. The processing of antigens produces roughly 100,000 to 300,000 peptide-laden HLA molecules on the dendritic cell surface, most peptides represented by about 100 copies. A single mature dendritic cell is capable of stimulating 100–3,000 T cells31-34.
    Immature dendritic cells are capable of phagocytosis of bacteria. Dendritic cell phagocytosis of Salmonella and Borrelia burgdorferi has been observed and studied. Immature dendritic cells roaming the lamina propria below the epithelial cells of the intestine not only capture bacteria which invade and cross the epithelial barrier, but have been observed reaching through the tight junctions between epithelial cells with their dendrite arms to directly sample non-invasive bacteria in the gut lumen and mucosa tissues outside the epithelium34-37.
    Immature dendritic cells express a variety of surface receptors which when stimulated cause dendritic cells to mature and respond in specific ways which can result in tolerance or immune activity. These receptors include Toll-like receptors (TLR), cytokine receptors, TNF (tumor necrosis factor) receptor, immunoglobulin (antibody) receptors, and sensors for cell death. TNF and other cykotine inflammatory mediators signal infections. In particular, interleukin-1 (IL-1) can prevent oral tolerance in mice by altering the response of normally tolerogenic dendritic cells into an active immune response32,34.
    Toll-like receptors are known as pattern recognition receptors which identify structural components found only on the surface of bacteria and other pathogens. These components are referred to as pathogen-associated molecular patterns (PAMPs). At least 10 types of TLR have been identified in humans and given the designations, TLR1-TLR10. Examples of PAMP include microbial carbohydrates like the toxin lipopolysaccharides (LPS), flagellin, products from bacterial cell walls, bacterial RNA and DNA. Signaling through different TLR evokes distinct biological responses. TLR expressed differently by different dendritic cell subsets may determine the manner in which dendritic cell subsets respond to particular microbial structures34,39.
    Mature dendritic cells can produce cytokines while activating CD4+ T cells which may influence T cell differentiation and function. Activated T cells divide and proliferate and differentiate into a variety of types. Tolerance and immunity induction are influenced most by differentiation into type 1 and type 2 helper T cells (Th1 and Th2) and regulatory T cells. The type of cytokines produced by the T cells determine their classification. Th2 responses favor tolerance. Th1 responses favor immunity and inflammation. Regulatory T cells suppress immune responses. IL-10 produced by dendritic cells appears to contribute to Th2 and regulatory T cell responses. Dendritic cell production of IL-12, IL-18, and IL-23 contribute to a Th1 response34,40.
    Why Does Tolerance to Gluten Fail?
    Okay. So why does the immune system fail to tolerate gluten in celiac disease? The immune system receives and responds to all kinds of signals from a pathogen, but how can a simple gluten peptide turn this complex immune machinery into a force against itself? Thinking about this leads to a very provocative question:
    What if instead of responding to gluten peptides alone, the immune system responds to a pathogenic gut bacteria which routinely ingests gluten peptides?
    A 33 amino acid gluten peptide has been identified as the primary initiator of the inflammatory response in celiac disease. This peptide contains a number of amino acid sequences which correspond to epitopes known to activate T cells and initiate celiac disease response. In particular, this 33-mer peptide was identified because it remained intact in the residue of a solution of gliadin mixed with gastric and pancreatic enzymes. This demonstrates some gluten peptides are difficult to breakdown by normal digestive processes. Another experiment identified a 17 amino acid gluten peptide which also contained epitopes associated with celiac disease41,42.
    Bacteria do not ingest nutrients in the normal sense. Nutrients are transported across cell membranes via several different mechanisms. Transported nutrients are necessarily limited in size. Nutrients are broken down externally by enzymes and by processes such as fermentation, an oxidation process resulting from acids produced by bacteria. Growth factors consisting of purines, pyrimidines, vitamins and amino acids are required by some bacteria in order to grow. Other bacteria are able to synthesize these essential growth factors. Researchers have found that some bacteria can transport and internalize amino acids in the form of peptides. Studies so far have found peptides up to 18 amino acids in length can be internalized by bacteria43-46.
    Epitopes of gluten peptides deamidated by tissue transglutaminase (tTG) are believed central to celiac disease pathogenesis. However, a study of gluten response in children with celiac disease found that T cells can respond to native gluten peptides independent of deamidation47. Celiac disease may begin its course without deamidation. As the disease progresses, inflammation may cause an increase in expression of tTG. An increase in tTG expression has been shown during wound healing, in liver injury, and in response to an inflammatory stimulus by lipopolysaccharide48-50. Through a process called epitope spreading and with the increase in tTG expression, deamidation of gluten peptides is more likely to occur and T cell response to deamidated gluten peptides likely develops. tTG is expressed in the epithelial brush border and extracellularly in the subepithelial region26 (The brush border is composed of the microvilli found on each individual epithelial cell).
    In the course of evolution of bacteria in the gut, it would seem highly plausible that at least one or more bacteria species have evolved and adapted in some way to transport, internalize and utilize gluten peptides as a source of amino acids. Since tTG is expressed in the epithelial brush border, deamidated gluten peptides are available to such bacteria (though in the early stage of celiac disease deamidation may not be required). If these bacteria colonize the gut and exhibit some pathogenic characteristic, such as expressing lipopolysaccharide, dendritic cells may be signaled to reach through the epithelial barrier into the lumen to sample and phagocytize the bacteria. When this bacteria is digested and processed by the dendritic cells, the antigens bound to HLA molecules and expressed on the dendritic cell surface are likely to include the difficult to breakdown, intact gluten peptides that have been internalized by the bacteria. As far as the immune system is concerned, these gluten peptides are indistinguishable from the other bacterial peptides bound to HLA molecules expressed on the dendritic cell surface. When these gluten peptide antigens are bound to HLA-DQ2 or -DQ8 molecules and presented to CD4+ T cells, the T cells simultaneously receive all the signals telling them that the gluten peptide is an antigen from a pathogenic bacteria. The result is that the immune system responds to the presence of gluten as though pathogenic bacteria were present. Such gluten-ingesting bacteria may be the missing link in the pathogenesis of Celiac Disease.
    If these bacteria exist, there is now a clear explanation as to why one identical twin may develop celiac disease and not the other. Of course, the presence of such a bacteria in the gut of one twin and not the other would fully explain the discordance. It is also possible that such a bacteria may exist in both twins, but is kept under control by the mix of commensal bacteria colonizing the gut of one twin. Some disturbance to this mix, such as an infection or use of antibiotics, might provide an opportunity for this gluten-ingesting bacteria to colonize and proliferate to a level where its pathogenic properties, such as production of endotoxins, are sensed by the immune system initiating the onset of celiac disease. The existence of such bacteria could also explain why there may be varying degrees of gluten sensitivity, even in individuals without DQ2 and DQ8 molecules.
    The possibility that these gluten-ingesting bacteria may exist raises another intriguing question: If these gluten-ingesting bacteria are controlled or eliminated from the gut, could tolerance to gluten be restored? There could be a very real possibility that celiac disease might be cured by eliminating these bacteria. After all, peptic ulcers can be cured by eliminating Helicobacter pylori.
    The Future
    So where should research go from here? The most obvious path would be first to try to find and identify any gut bacteria that has gluten peptides present within its cell membranes. From there, the possible link to celiac disease could be studied. Additionally, it would be quite valuable to initiate a large long-term study of the makeup of commensal bacteria in identical twins beginning at birth via fecal samples. By comparing the differences in microflora and the onset and discordance of diseases in identical twins over many years, the relationships of specific species of bacteria to specific diseases, including celiac disease, could be established. And if it proves to be true that gluten-ingesting bacteria cause celiac disease, a similar mechanism involving bacteria and peptides from other proteins may be the root cause for many other autoimmune diseases. A whole class of autoimmune diseases might be cured by eliminating specific species of bacteria.
    Roy Jamron holds degrees in physics and engineering from the University of Michigan and the University of California at Davis and actively pursues and investigates research on celiac disease and related disorders.

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    Greco L, Romino R, Coto I, Di Cosmo N, Percopo S, Maglio M, Paparo F, Gasperi V, Limongelli MG, Cotichini R, D'Agate C, Tinto N, Sacchetti L, Tosi R, Stazi MA. The first large population based twin study of coeliac disease. Gut 2002 May;50(5):624-8. Bardella MT, Fredella C, Prampolini L, Marino R, Conte D, Giunta AM. Gluten sensitivity in monozygous twins: a long-term follow-up of five pairs. Am J Gastroenterol 2000 Jun;95(6):1503-5. Bingley PJ, Williams AJ, Norcross AJ, Unsworth DJ, Lock RJ, Ness AR, Jones RW. Undiagnosed coeliac disease at age seven: population based prospective birth cohort study. BMJ 2004 Feb 7;328(735):322-3. Sollid LM. Breast milk against coeliac disease. Gut 2002 Dec;51(6):767-8. Nash S. Does exclusive breast-feeding reduce the risk of coeliac disease in children? Br J Community Nurs 2003 Mar;8(3):127-32. Ivarsson A, Hernell O, Stenlund H, Persson LA. Breast-feeding protects against celiac disease. Am J Clin Nutr 2002 May;75(5):914-21. Peters U, Schneeweiss S, Trautwein EA, Erbersdobler HF. A case-control study of the effect of infant feeding on celiac disease. Ann Nutr Metab 2001;45(4):135-42. Stepankova R, Kofronova O, Tuckova L, Kozakova H, Cebra JJ, Tlaskalova-Hogenova H. Experimentally induced gluten enteropathy and protective effect of epidermal growth factor in artificially fed neonatal rats. J Pediatr Gastroenterol Nutr 2003 Jan;36(1):96-104. Martin R, Langa S, Reviriego C, Jiminez E, Marin ML, Xaus J, Fernandez L, Rodriguez JM. Human milk is a source of lactic acid bacteria for the infant gut. J Pediatr 2003 Dec;143(6):754-8. Goldman AS. Modulation of the gastrointestinal tract of infants by human milk. Interfaces and interactions. An evolutionary perspective. J Nutr 2000 Feb;130(2S Suppl):426S-431S. Fanaro S, Chierici R, Guerrini P, Vigi V. Intestinal microflora in early infancy: composition and development. Acta Paediatr Suppl 2003 Sep;91(441):48-55. Dunne C, O'Mahony L, Murphy L, Thornton G, Morrissey D, O'Halloran S, Feeney M, Flynn S, Fitzgerald G, Daly C, Kiely B, O'Sullivan GC, Shanahan F, Collins JK. In vitro selection criteria for probiotic bacteria of human origin: correlation with in vivo findings. Am J Clin Nutr 2001 Feb;73(2 Suppl):386S-392S. Mai V, Morris JG Jr. Colonic bacterial flora: changing understandings in the molecular age. J Nutr 2004 Feb;134(2):459-64 Gronlund MM, Arvilommi H, Kero P, Lehtonen OP, Isolauri E. Importance of intestinal colonisation in the maturation of humoral immunity in early infancy: a prospective follow up study of healthy infants aged 0-6 months. Arch Dis Child Fetal Neonatal Ed 2000 Nov;83(3):F186-92. Hooper LV, Wong MH, Thelin A, Hansson L, Falk PG, Gordon JI. Molecular analysis of commensal host-microbial relationships in the intestine. Science 2001 Feb 2;291(5505):881-4. Hooper LV, Xu J, Falk PG, Midtvedt T, Gordon JI. A molecular sensor that allows a gut commensal to control its nutrient foundation in a competitive ecosystem. Proc Natl Acad Sci U S A 1999 Aug 17;96(17):9833-8. Stappenbeck TS, Hooper LV, Gordon JI. Developmental regulation of intestinal angiogenesis by indigenous microbes via Paneth cells. Proc Natl Acad Sci U S A 2002 Nov 26;99(24):15451-5. Hooper LV, Stappenbeck TS, Hong CV, Gordon JI. Angiogenins: a new class of microbicidal proteins involved in innate immunity. Nat Immunol 2003 Mar;4(3):269-73. Lanning D, Sethupathi P, Rhee KJ, Zhai SK, Knight KL. Intestinal microflora and diversification of the rabbit antibody repertoire. J Immunol 2000 Aug 15;165(4):2012-9. Rhee KJ, Sethupathi P, Driks A, Lanning DK, Knight KL. Role of commensal bacteria in development of gut-associated lymphoid tissues and preimmune antibody repertoire. J Immunol 2004 Jan 15;172(2):1118-24. Garcia-Lafuente A, Antolin M, Guarner F, Crespo E, Malagelada JR. Modulation of colonic barrier function by the composition of the commensal flora in the rat. Gut 2001 Apr;48(4):503-7. Bai AP, Ouyang Q, Zhang W, Wang CH, Li SF. Probiotics inhibit TNF-alpha-induced interleukin-8 secretion of HT29 cells. World J Gastroenterol 2004 Feb 1;10(3):455-7. Guarner F, Malagelada JR. Gut flora in health and disease. Lancet 2003 Feb 8;361(9356):512-9. Hill MJ. Intestinal flora and endogenous vitamin synthesis. Eur J Cancer Prev 1997 Mar;6 Suppl 1:S43-5. Card T, Logan RF, Rodrigues LC, Wheeler JG. Antibiotic use and the development of Crohn's disease. Gut 2004 Feb;53(2):246-50. Sollid LM. Coeliac disease: dissecting a complex inflammatory disorder. Nat Rev Immunol 2002 Sep;2(9):647-55. Dewar D, Pereira SP, Ciclitira PJ. The pathogenesis of coeliac disease. Int J Biochem Cell Biol 2004 Jan;36(1):17-24. Farrell RJ, Kelly CP. Celiac sprue. N Engl J Med 2002 Jan 17;346(3):180-8. Daum S, Bauer U, Foss HD, Schuppan D, Stein H, Riecken EO, Ullrich R. Increased expression of mRNA for matrix metalloproteinases-1 and -3 and tissue inhibitor of metalloproteinases-1 in intestinal biopsy specimens from patients with coeliac disease. Gut 1999 Jan;44(1):17-25. Louka AS, Sollid LM. HLA in coeliac disease: unravelling the complex genetics of a complex disorder. Tissue Antigens 2003 Feb;61(2):105-17. DeMeyer ES, Baar J. Dendritic Cells: The Sentry Cells of the Immune System. Oncology Education Services, Inc. http://oes.digiton.com/dcell/ Guermonprez P, Valladeau J, Zitvogel L, Thery C, Amigorena S. Antigen presentation and T cell stimulation by dendritic cells. Annu Rev Immunol 2002;20:621-67. Klein J, Sato A. The HLA system. First of two parts. N Engl J Med 2000 Sep 7;343(10):702-9. Stagg AJ, Hart AL, Knight SC, Kamm MA. The dendritic cell: its role in intestinal inflammation and relationship with gut bacteria. Gut 2003 Oct;52(10):1522-9. Sundquist M, Rydstrom A, Wick MJ. Immunity to Salmonella from a dendritic point of view. Cell Microbiol 2004 Jan;6(1):1-11. Suhonen J, Komi J, Soukka J, Lassila O, Viljanen MK. Interaction between Borrelia burgdorferi and immature human dendritic cells. Scand J Immunol 2003 Jul;58(1):67-75. Uhlig HH, Powrie F. Dendritic cells and the intestinal bacterial flora: a role for localized mucosal immune responses. J Clin Invest 2003 Sep;112(5):648-51. Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P. Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol 2001 Apr;2(4):361-7. Singh BP, Chauhan RS, Singhal LK. Toll-like receptors and their role in innate immunity. Current Science 2003 Oct;85(8):1156-1164. Mowat AM. Anatomical basis of tolerance and immunity to intestinal antigens. Nat Rev Immunol 2003 Apr;3(4):331-41. Shan L, Molberg O, Parrot I, Hausch F, Filiz F, Gray GM, Sollid LM, Khosla C. Structural basis for gluten intolerance in celiac sprue. Science 2002 Sep 27;297(5590):2275-9. Anderson RP, Degano P, Godkin AJ, Jewell DP, Hill AV. In vivo antigen challenge in celiac disease identifies a single transglutaminase-modified peptide as the dominant A-gliadin T-cell epitope. Nat Med 2000 Mar;6(3):337-42. Todar K. Todar's Online Textbook of Bacteriology. Univ of Wisconsin Department of Bacteriology. http://www.textbookofbacteriology.net Monnet V. Bacterial oligopeptide-binding proteins. Cell Mol Life Sci 2003 Oct;60(10):2100-14. Foucaud C, Hemme D, Desmazeaud M. Peptide utilization by Lactococcus lactis and Leuconostoc mesenteroides. Lett Appl Microbiol 2001 Jan;32(1):20-5. Detmers FJ, Kunji ER, Lanfermeijer FC, Poolman B, Konings WN. Kinetics and specificity of peptide uptake by the oligopeptide transport system of Lactococcus lactis. Biochemistry 1998 Nov 24;37(47):16671-9. Vader W, Kooy Y, Van Veelen P, De Ru A, Harris D, Benckhuijsen W, Pena S, Mearin L, Drijfhout JW, Koning F. The gluten response in children with celiac disease is directed toward multiple gliadin and glutenin peptides. Gastroenterology 2002 Jun;122(7):1729-37. Haroon ZA, Hettasch JM, Lai TS, Dewhirst MW, Greenberg CS. Tissue transglutaminase is expressed, active, and directly involved in rat dermal wound healing and angiogenesis. FASEB J 1999 Oct;13(13):1787-95. Nardacci R, Lo Iacono O, Ciccosanti F, Falasca L, Addesso M, Amendola A, Antonucci G, Craxi A, Fimia GM, Iadevaia V, Melino G, Ruco L, Tocci G, Ippolito G, Piacentini M. Transglutaminase type II plays a protective role in hepatic injury. Am J Pathol 2003 Apr;162(4):1293-303. Bowness JM, Tarr AH. Increase in transglutaminase and its extracellular products in response to an inflammatory stimulus by lipopolysaccharide. Mol Cell Biochem 1997 Apr;169(1-2):157-63.

    Jefferson Adams
    Patients Diagnosed in Childhood Might Evolve toward Latency on a Normal Diet
    Celiac.com 05/23/2007 - The results of a study recently published in the journal Gut indicate that some people who suffer from celiac disease might not need to remain on a gluten free diet for their entire lives, and that some celiac patients might be able to safely introduce gluten containing foods without suffering a relapse.
    Previous Studies Showing Positive Response to Wheat Introduction in Patients with Celiac Disease are Promising, But Incomplete
    Several studies have shown that some patients diagnosed with celiac disease in childhood were able to remain on a gluten-containing diet after gluten challenge without suffering a relapse. However, most of these studies included a small number of patients, or followed the patients for only a short period after gluten was reintroduced into their diets.
    These previous studies also limited their evaluation largely to assessment of celiac disease serology and histology of duodenal biopsies, and did not attempt to identify what factors might predict the development of tolerance to gluten.
    Determining Long-term Response to Gluten Consumption in Celiac Disease Patients
    A research team made up of doctors Tamara Matysiak-Budnik (1), Georgia Malamut (1,2), Natacha Patey-Mariaud de Serre (3), Etienne Grosdidier (2), Sylvie Seguier (3), Nicole Brousse (3), Sophie Caillat-Zucman (4), Nadine Cerf-bensussan (1), Jacques Schmitz (5) and Christophe Cellier (1,2), set out to determine whether children diagnosed with celiac disease must follow a gluten free diet for life.
    To determine the effects of reintroducing gluten into the diets of celiac patients, the research team set out to monitor the clinical and physical progress of adult celiac patients who had been diagnosed as children, who underwent a gluten challenge, and who were asymptomatic.
    The study focused on a specific group of patients, all but two of whom were diagnosed as children and followed until adulthood in the Department of Pediatric Gastroenterology in Necker Hospital and thereafter at the Georges Pompidou European Hospital in Paris; after which, they were entered into a local register of adult celiac patients and were recruited for the study based on two criteria: celiac disease diagnosed in childhood; and adherence to a normal diet.
    The patients in the study were from 18 to 65 years old, and had been diagnosed with celiac disease in childhood. The research team recorded data in the following categories: biological parameters of malabsorption; bone mineral density; clinical celiac status; gluten intake; HLA genotype; serological markers of celiac disease; as well as histological and immuno-histochemical parameters in duodenal biopsies.

    Results Show 20% Long-term Latency in Celiac Patients who Eat Normal Diet
    Of those studied, 61 patients had returned to a normal diet, and were asymptomatic. 48 showed various degrees of villous atrophy (silent celiac disease), and 13 had no detectable atrophy (latent celiac disease) on duodenal biopsies. Compared to those with silent celiac disease, patients with latent celiac disease showed markedly less osteopenia/osteoporosis [1/9 (11%) versus 23/33 (70%), p<0.001)], and lower TcR- + intraepithelial T cell counts (38±20 vs. 55±15, p<0.01).
    Patients with latent celiac disease had a lower mean age at the time of their first gluten free diet compared to patients with silent celiac disease (14.4±5 vs 40.1±47 months, p<0.05).
    Compared to the seven control patients on a long-term gluten free diet, the latent patients did not differ significantly, except for a higher frequency of celiac disease-specific serum antibodies. However, a follow-up found that two of the patients with latent celiac disease had suffered a clinical and histological relapse.
    Results showed that of those patients who remained asymptomatic after the reintroduction of gluten, 20% showed long-term latency.
    The study concludes that some patients with celiac disease may not need to remain on a life-long gluten free diet, and that some may indeed be able to safely reintroduce gluten into their diets with no adverse effects. However, the latency patients may experience may be transient, and therefore a regular follow-up is necessary. Also, patients with silent celiac disease should remain on a gluten free diet.
    Participating hospitals:
    (1) INSERM, U793, Faculté de Médecine René Descartes, IFR94, Paris, France.
    (2) AP-HP, H&OCIRC;pital Européen Georges Pompidou, Department of Hepato-Gastroenterology,
    Paris, France.
    (3) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pathology, Paris, France.
    (4) INSERM, Equipe Avenir, Faculté de Médecine René Descartes, Paris, France.
    (5) AP-HP, H&OCIRC;pital Necker-Enfants Malades, Department of Pediatric Gastroenterology, Paris, France.
    Gut 2006;13(10).
    Comments on this Study by Ron Hoggan
    This is dressed up like a new finding, but it isn't. There are a number of studies that show similar findings. Part of that problem lies in the interpretation of the biopsies, and part of the problem arises out of failing to recognize the variable nature of the disease. It has long been known to wax and wane for reasons beyond our ken. Samuel Gee (1888) and Gibbons (1889) both reported the cyclic nature of their patients symptoms. They cited a study to support the idea of a two year rule saying that relapse would usually occur within two years, yet Kuitunen P, Savilahti E, Verkasalo M., in Late mucosal relapse in a boy with coeliac disease and cows milk allergy. Acta Paediatr Scand. 1986 Mar;75(2):340-2. reported one patient who at 4.3 years on a normal diet showed normal villous architecture. It was not until a follow-up biopsy at more than 8 years of eating a gluten-containing diet that he showed villous atrophy. These findings, along with all the other studies that have shown long delays in some patients before relapsing, argue strongly for Michael N. Marsh's position that we should concentrate on treating any immune system that is sensitized to gluten with a gluten-free diet. His rectal challenge is an excellent tool for identifying such sensitized immune systems. Dr. Fines fecal antibody test probably fits into the same category. The underlying assumption is that the biopsy will identify all cases of intestinal lesion regardless of the possibility of patchy lesions that are well documented in the literature. They deal with increased IEL counts as if they were a feature of latent celiac disease when that is not the case. There are several other points on which this study falters. They admit that the latency can be transient. Unfortunately, they have not exchanged emails with people where they have returned to eating gluten and have developed an abdominal cancer. I exchanged emails with such a young man who blamed himself for having killed himself with his carelessness about his diet. How awful that was for him! Yet these authors seem to think it is quite acceptable for patients to indulge during their latency periods and only consider a diet if there is a relapse of intestinal lesion.
     

    Jefferson Adams
    Celiac.com 12/03/2012 - Gluten sensitivity has recently been added to the spectrum of gluten-related disorders, but precise diagnostic markers do not yet exist. A research team recently set out to understand the blood test pattern of gluten sensitivity, and to compare it with the blood test pattern seen in celiac disease.
    The researchers included U. Volta, F. Tovoli, R. Cicola, C. Parisi, A. Fabbri, M. Piscaglia, E. Fiorini, G. Caio, of the Department of Clinical Medicine at University of Bologna's St. Orsola-Malpighi Hospital in Bologna, Italy.
    For their study, the researchers looked at blood samples from 78 patients with gluten-sensitivity and 80 patients with celiac disease. They assessed levels of immunoglobulin (Ig)G/IgA antigliadin antibodies (AGA), IgG deamidated gliadin peptide antibodies (DGP-AGA), IgA tissue transglutaminase antibodies (tTGA), and IgA endomysial antibodies (EmA).
    They found positive readings for IgG AGA in 56.4% of patients with gluten-sensitivity, and in 81.2% of patients with celiac disease. Antibody levels for both groups were in the high range.
    They found IgA AGA in 7.7% of patients with gluten-sensitivity, and in 75% of patients with celiac disease, which shows lower enzyme-linked immunosorbent assay activities in gluten-sensitivity patients than in patients with celiac disease.
    Only 1 of the 78 patients with gluten-sensitivity tested positive for IgG DGP-AGA, which was found in nearly 90% of patients with celiac disease.
    All patients with gluten-sensitivity tested negative for IgA tTGA and IgA EmA, while 98.7% of patients with celiac disease tested positive for IgA tTGA, and 95% were positive for IgA EmA.
    Patients with gluten-sensitivity presented a variety of intestinal and extra-intestinal symptoms, including abdominal pain, bloating, diarrhea, constipation, foggy mind, tiredness, eczema/skin rash, headache, joint/muscle pain, numbness of legs/arms, depression, and anemia. Small intestinal mucosa for these patients was either normal or only mildly abnormal.
    The data from these blood tests show that more than half of patients with gluten sensitivity will test positive for IgG AGA, and a small number will test positive for IgA AGA, but none will show positive results for EmA, tTGA, and DGP-AGA, which are the specific markers of celiac disease.
    Source:
    J Clin Gastroenterol. 2012 Sep;46(8):680-5.

    Jefferson Adams
    Celiac.com 02/04/2015 - For kids with a predisposition to celiac disease, does the age at which they first eat gluten have any connection with their risk for celiac disease? A team of researchers wanted to figure out whether the age at which a child first eats gluten carried any associated with risk for celiac disease, for genetically predisposed children. The Environmental Determinants of Diabetes in the Young (TEDDY) is a prospective birth cohort study.
    The research team included Carin Andrén Aronsson, MSca, Hye-Seung Lee, PhD, Edwin Liu, MD, PhD, Ulla Uusitalo, PhD, Sandra Hummel, PhD, Jimin Yang, PhD, RD, Michael Hummel, MD, PhD, Marian Rewers, MD, PhD, Jin-Xiong She, PhD, Olli Simell, MD, PhD, Jorma Toppari, MD, PhD, Anette-G. Ziegler, MD, PhD, Jeffrey Krischer, PhD, Suvi M. Virtanen, MD, PhD, Jill M. Norris, MPH, PhD, and Daniel Agardh, MD, PhD, for the The Environmental Determinants of Diabetes in the Young (TEDDY) Study Group.
    They are variously affiliated with the Department of Clinical Sciences, Lund University, Malmö, Sweden; the Pediatrics Epidemiology Center at the Department of Pediatrics of the Morsani College of Medicine at University of South Florida in Tampa, Florida; the Digestive Health Institute at the University of Colorado, Children’s Hospital Colorado in Denver; the Barbara Davis Center for Childhood Diabetes at the University of Colorado in Aurora, Colorado; the Department of Epidemiology, Colorado School of Public Health, University of Colorado at Denver in Aurora, Colorado; the Institute of Diabetes Research, Helmholtz Zentrum München, and Klinikum rechts der Isar, Technische Universität München, and Forschergruppe Diabetes e.V., Neuherberg, Germany; The Center for Biotechnology and Genomic Medicine, Medical College of Georgia, Georgia Regents University, Augusta, Georgia; Department of Pediatrics, Turku University Hospital, Turku, Finland; the Department of Physiology and Pediatrics, University of Turku, Turku, Finland; the National Institutes for Health and Welfare, Nutrition Unit, Helsinki, Finland; the School of Health Sciences, University of Tampere, Tampere, Finland; and the Research Center for Child Health at Tampere University and University Hospital and the Science Center of Pirkanmaa Hospital District, Tampere, Finland.
    For their study, the team followed up on 6,436 newborn infants who had been screened for high-risk HLA-genotypes for celiac disease in Finland, Germany, Sweden, and the United States.
    At clinical visits every third month, the team collected information about infant feeding.
    The first outcome was persistent positive for tissue transglutaminase autoantibodies (tTGA), the marker for celiac disease.
    The second outcome was celiac disease, defined as either a diagnosis based on intestinal biopsy results, or as persistently high levels of tTGA.
    The team found that Swedish children consumed their first gluten at an earlier age, 21.7 weeks on average, compared with 26.1 weeks for children from Finland, and just over 30 weeks for kids from Germany, and the United States (P < .0001).
    Over about a follow-up period ranging from 1.7–8.8 years, but averaging about five years, the team found that 773 (12%) children developed tTGA and 307 (5%) developed celiac disease.
    Compared with US children, Swedish children saw an increased risk for tTGA, with a hazard ratio of 1.74 [95% CI: 1.47–2.06]) and celiac disease, with a hazard ratio of 1.76 [95% CI: 1.34–2.24]), respectively (P < .0001).
    Gluten introduction before kids turn 17 weeks or after 26 weeks was not associated with increased risk for tTGA or celiac disease, adjusted for country, HLA, gender, and family history of celiac disease, neither in the overall analysis nor on a country-level comparison.
    TEDDY, is one of several recent studies that confirm that the age at first gluten introduction was not an independent risk factor for developing celiac disease.
    Source:
    Pediatrics; January 19, 2015. doi: 10.1542/peds.2014-1787

  • Recent Articles

    Jefferson Adams
    Celiac.com 07/19/2018 - Maintaining a gluten-free diet can be an on-going challenge, especially when you factor in all the hidden or obscure gluten that can trip you up. In many cases, foods that are naturally gluten-free end up contain added gluten. Sometimes this can slip by us, and that when the suffering begins. To avoid suffering needlessly, be sure to keep a sharp eye on labels, and beware of added or hidden gluten, even in food labeled gluten-free.  Use Celiac.com's SAFE Gluten-Free Food List and UNSAFE Gluten-free Food List as a guide.
    Also, beware of these common mistakes that can ruin your gluten-free diet. Watch out for:
    Watch out for naturally gluten-free foods like rice and soy, that use gluten-based ingredients in processing. For example, many rice and soy beverages are made using barley enzymes, which can cause immune reactions in people with celiac disease. Be careful of bad advice from food store employees, who may be misinformed themselves. For example, many folks mistakenly believe that wheat-based grains like spelt or kamut are safe for celiacs. Be careful when taking advice. Beware of cross-contamination between food store bins selling raw flours and grains, often via the food scoops. Be careful to avoid wheat-bread crumbs in butter, jams, toaster, counter surface, etc. Watch out for hidden gluten in prescription drugs. Ask your pharmacist for help about anything you’re not sure about, or suspect might contain unwanted gluten. Watch out for hidden gluten in lotions, conditioners, shampoos, deodorants, creams and cosmetics, (primarily for those with dermatitis herpetaformis). Be mindful of stamps, envelopes or other gummed labels, as these can often contain wheat paste. Use a sponge to moisten such surfaces. Be careful about hidden gluten in toothpaste and mouthwash. Be careful about common cereal ingredients, such as malt flavoring, or other non-gluten-free ingredient. Be extra careful when considering packaged mixes and sauces, including soy sauce, fish sauce, catsup, mustard, mayonnaise, etc., as many of these can contain wheat or wheat by-product in their manufacture. Be especially careful about gravy mixes, packets & canned soups. Even some brands of rice paper can contain gluten, so be careful. Lastly, watch out for foods like ice cream and yogurt, which are often gluten-free, but can also often contain added ingredients that can make them unsuitable for anyone on a gluten-free diet. Eating Out? If you eat out, consider that many restaurants use a shared grill or shared cooking oil for regular and gluten-free foods, so be careful. Also, watch for flour in otherwise gluten-free spices, as per above. Ask questions, and stay vigilant.

    Jefferson Adams
    Celiac.com 07/18/2018 - Despite many studies on immune development in children, there still isn’t much good data on how a mother’s diet during pregnancy and infancy influences a child’s immune development.  A team of researchers recently set out to assess whether changes in maternal or infant diet might influence the risk of allergies or autoimmune disease.
    The team included Vanessa Garcia-Larsen, Despo Ierodiakonou, Katharine Jarrold, Sergio Cunha,  Jennifer Chivinge, Zoe Robinson, Natalie Geoghegan, Alisha Ruparelia, Pooja Devani, Marialena Trivella, Jo Leonardi-Bee, and Robert J. Boyle.
    They are variously associated with the Department of Undiagnosed Celiac Disease More Common in Women and Girls International Health, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America; the Respiratory Epidemiology, Occupational Medicine and Public Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom; the Section of Paediatrics, Department of Medicine, Imperial College London, London, United Kingdom; the Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom; the Division of Epidemiology and Public Health, University of Nottingham, Nottingham, United Kingdom; the Centre of Evidence Based Dermatology, University of Nottingham, Nottingham, United Kingdom; and Stanford University in the USA.
    Team members searched MEDLINE, Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) for observational studies conducted between January 1946 and July 2013, and interventional studies conducted through December 2017, that evaluated the relationship between diet during pregnancy, lactation, or the first year of life, and future risk of allergic or autoimmune disease. 
    They then selected studies, extracted data, and assessed bias risk. They evaluated data using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). They found 260 original studies, covering 964,143 participants, of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies, covering 542,672 participants, of other maternal or infant dietary exposures, including 80 trials of 26 maternal, 32 infant, or 22 combined interventions. 
    They found a high bias risk in nearly half of the more than 250 milk feeding studies and in about one-quarter of studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with probiotics during late pregnancy and lactation may reduce risk of eczema. 44 cases per 1,000; 95% CI 20–64), and 6 trials, suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitization to egg. GRADE certainty of these findings was moderate. 
    The team found less evidence, and low GRADE certainty, for claims that breastfeeding reduces eczema risk during infancy, that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus, and that probiotics reduce risk of infants developing allergies to cow’s milk. 
    They found no evidence that dietary exposure to other factors, including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake, influence risk of allergic or autoimmune disease. 
    Overall, the team’s findings support a connection between the mother’s diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitization to food, respectively.
    Stay tuned for more on diet during pregnancy and its role in celiac disease.
    Source:
    PLoS Med. 2018 Feb; 15(2): e1002507. doi:  10.1371/journal.pmed.1002507

    Jefferson Adams
    Celiac.com 07/17/2018 - What can fat soluble vitamin levels in newly diagnosed children tell us about celiac disease? A team of researchers recently assessed fat soluble vitamin levels in children diagnosed with newly celiac disease to determine whether vitamin levels needed to be assessed routinely in these patients during diagnosis.
    The researchers evaluated the symptoms of celiac patients in a newly diagnosed pediatric group and evaluated their fat soluble vitamin levels and intestinal biopsies, and then compared their vitamin levels with those of a healthy control group.
    The research team included Yavuz Tokgöz, Semiha Terlemez and Aslıhan Karul. They are variously affiliated with the Department of Pediatric Gastroenterology, Hepatology and Nutrition, the Department of Pediatrics, and the Department of Biochemistry at Adnan Menderes University Medical Faculty in Aydın, Turkey.
    The team evaluated 27 female, 25 male celiac patients, and an evenly divided group of 50 healthy control subjects. Patients averaged 9 years, and weighed 16.2 kg. The most common symptom in celiac patients was growth retardation, which was seen in 61.5%, with  abdominal pain next at 51.9%, and diarrhea, seen in 11.5%. Histological examination showed nearly half of the patients at grade Marsh 3B. 
    Vitamin A and vitamin D levels for celiac patients were significantly lower than the control group. Vitamin A and vitamin D deficiencies were significantly more common compared to healthy subjects. Nearly all of the celiac patients showed vitamin D insufficiency, while nearly 62% showed vitamin D deficiency. Nearly 33% of celiac patients showed vitamin A deficiency. 
    The team saw no deficiencies in vitamin E or vitamin K1 among celiac patients. In the healthy control group, vitamin D deficiency was seen in 2 (4%) patients, vitamin D insufficiency was determined in 9 (18%) patients. The team found normal levels of all other vitamins in the healthy group.
    Children with newly diagnosed celiac disease showed significantly reduced levels of vitamin D and A. The team recommends screening of vitamin A and D levels during diagnosis of these patients.
    Source:
    BMC Pediatrics

    Jefferson Adams
    Celiac.com 07/16/2018 - Did weak public oversight leave Arizonans ripe for Theranos’ faulty blood tests scam? Scandal-plagued blood-testing company Theranos deceived Arizona officials and patients by selling unproven, unreliable products that produced faulty medical results, according to a new book by Wall Street Journal reporter, whose in-depth, comprehensive investigation of the company uncovered deceit, abuse, and potential fraud.
    Moreover, Arizona government officials facilitated the deception by providing weak regulatory oversight that essentially left patients as guinea pigs, said the book’s author, investigative reporter John Carreyrou. 
    In the newly released "Bad Blood: Secrets and Lies in a Silicon Valley Startup," Carreyrou documents how Theranos and its upstart founder, Elizabeth Holmes, used overblown marketing claims and questionable sales tactics to push faulty products that resulted in consistently faulty blood tests results. Flawed results included tests for celiac disease and numerous other serious, and potentially life-threatening, conditions.
    According to Carreyrou, Theranos’ lies and deceit made Arizonans into guinea pigs in what amounted to a "big, unauthorized medical experiment.” Even though founder Elizabeth Holmes and Theranos duped numerous people, including seemingly savvy investors, Carreyrou points out that there were public facts available to elected officials back then, like a complete lack of clinical data on the company's testing and no approvals from the Food and Drug Administration for any of its tests.
    SEC recently charged the now disgraced Holmes with what it called a 'years-long fraud.’ The company’s value has plummeted, and it is now nearly worthless, and facing dozens, and possibly hundreds of lawsuits from angry investors. Meantime, Theranos will pay Arizona consumers $4.65 million under a consumer-fraud settlement Arizona Attorney General Mark Brnovich negotiated with the embattled blood-testing company.
    Both investors and Arizona officials, “could have picked up on those things or asked more questions or kicked the tires more," Carreyrou said. Unlike other states, such as New York, Arizona lacks robust laboratory oversight that would likely have prevented Theranos from operating in those places, he added.
    Stay tuned for more new on how the Theranos fraud story plays out.
    Read more at azcentral.com.

    Jefferson Adams
    Celiac.com 07/14/2018 - If you’re looking for a simple, nutritious and exciting alternative to standard spaghetti and tomato sauce, look no further than this delicious version that blends ripe plum tomatoes, garlic, olive oil, basil, and firm sliced ricotta to deliver a tasty, memorable dish.
    Ingredients:
    12 ounces gluten-free spaghetti 5 or 6 ripe plum tomatoes ¼ cup extra virgin olive oil 2 cloves garlic, crushed ¾ teaspoons crushed red pepper ¼ cup chopped fresh basil 2 tablespoons chopped fresh parsley Kosher salt and black pepper ⅓ cup pecorino Romano cheese, grated ½ cup firm ricotta, shaved with peeler Directions:
    Finely chop all but one of the tomatoes; transfer to large bowl with olive oil and ¼ teaspoon salt.
    Cook spaghetti until al dente or desired firmness, and drain, reserving ¼ cup cooking water. 
    Meanwhile, chop remaining tomato, and place in food processor along with garlic, red pepper, and ½ teaspoon salt; puree until smooth. 
    Gently stir mixture into the bowl of chopped tomatoes.
    Add cooked spaghetti, basil and parsley to a large bowl.
    Toss in tomato mixture, adding some reserved pasta water, if needed. 
    Spoon pasta into bowls and top with Romano cheese, as desired.