Gluten sensitivity

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This article is part of
the Gluten sensitivity
series.
Coeliac disease
Wheat allergy
Gluten-sensitive idiopathic neuropathies
Dermatitis herpetiformis
Oat sensitivity
Triticeae glutens
Gluten-free diet
GSE associated conditions
Anti-gliadin antibodies
Anti-transglutaminase antibodies
HLA-DQ2, HLA-DQ8

Gluten sensitivity (GS) encompasses a collection of medical conditions in which gluten has an adverse effect. For individuals with gluten-sensitive enteropathy, removal of gluten generally results in the restoration of villus architecture[1] or lower lymphocyte densities in the intestine.[2] With some sensitivities, improvements may be seen in the neurological state, but a clinical finding may not be clear.[3][4] GS also can affect blood chemistry,[5] treatability of certain autoimmune diseases,[6] and/or an untreated improvement in autoimmune conditions.[7][8][9]

Gluten is composed of the sticky, storage proteins found in wheat. Gluten-sensitive enteropathy (GSE) describes the small intestinal pathology caused by gluten. Gluten induces an innate immune response and T-helper cell response in genetically susceptible individuals. This differs from wheat allergies (mast cell and IgE responses) can be directed toward a variety of wheat proteins, with certain gluten components a frequent target. Some unusual allergies to gluten can result in anaphylaxis while others may be difficult to diagnose. Idiopathic gluten sensitivity (IGS) arises "spontaneously or from an obscure or unknown cause" and may involve neuropathy, myopathy, dermal, or intestinal abnormalities. Anti-gliadin antibodies are the primary link between gluten and idiopathic sensitivity in instances in which enteropathy or allergy are not clearly involved.[10]

4 different commercial forms of Triticeae cultivars. Clockwise from top: wheat gluten flour, European spelt, barley corns, rolled rye
4 different commercial forms of Triticeae cultivars. Clockwise from top: wheat gluten flour, European spelt, barley corns, rolled rye

The relationship between gluten and these various sensitivities is complex. For gluten enteropathy, T-cell reactivity almost entirely restricted to prolamin-glutelin/species within the grass tribe Triticeae.[11][12] For some 2% of GSE, it may also include some pure oat cultivars.[13] Gluten allergies may extend over wide taxa or may be specific to certain wheat proteins.

Contents

[edit] Causes of gluten sensitivity

Triticeae and the potential role of selective evolution in gluten sensitivities. Some of the recently discovered biochemical and immunochemical properties of these proteins suggest they evolved for protection against dedicated or continuous consumption by mammalian seed eaters. One recent publication even raises the question 'is wheat safe for anyone to eat?'.[14] The role of wheat in gluten-sensitive enteropathy points prominently toward 2 regions of alpha gliadin, regions that contain two motifs, an innate immunity and a cellular-immunity (T-cell) recognition site, these sites are poorly digested in the gut. The target of both GSE and IGS appear to be regions of this protein(s). Recently, it has been found that alpha-gliadin targets cell surface CXCR3 and increases permeability of the cells forming the epithelia of the small intestine, explaining how gliadin peptides are able to stimulate monocytes and T-cells within the intestinal villi.[15]

Gluten allergies have no specific cause, other than GSE itself in many cases, as allergies react to a wide variety of proteins in wheat. The rise of gluten sensitivity (particularly in adults) appears to reflect overconsumption of wheat, feeding habits of small children, overuse of intestine damaging chemicals (MSG, aspirin, NSAIDs), and allergy-enhancing chemical treatment of wheat (enzymatic deamidation). These agents may act together with the proinflammatory activities of gluten, the "19mer" and CXCR3 binding epitope, to stimulate inflammatory response to gluten.

[edit] Gluten-sensitive enteropathy

Schematic of the Marsh classification of upper jejunal pathology in coeliac disease
Schematic of the Marsh classification of upper jejunal pathology in coeliac disease

Gluten sensitivity may precede coeliac disease in the progression of gluten sensitive enteropathy (GSE). The diagnostic "gold standard" of coeliac disease as the villus atrophy detected in duodenal biopsies. However, it is now recognized that inflammation of the epithelial tissue of the small intestine precedes atrophy. Early in the disease, gluten elicits T-lymphocyte recognition of gluten hydrolysates (polypeptides of gluten) and gluten peptides bind to mammalian tissue transglutaminase (tTG). This second interaction results in the production of "self" antibodies to tTG. This increases lymphocytes within the epithelia of the small intestine (Marsh grade 1 and 2) and antibody-tTG complexes seen as deposits. This usually progresses to coeliac disease (Marsh grade 3 and 4). The dietary cause of GSE is not limited to wheat gluten, 'glutens' from all known edible cultivars of Triticeae can induce GSE in susceptible individuals (see: Gluten Immunochemistry).

Main article: Coeliac disease (CD)

There are a large number of medical conditions that result from GSE that can occur prior to the development of coeliac disease and maybe gluten responsive. While the level of villus atropy in some cases of GSE may not reach clinical coeliac disease recognition, the elevation of cellular immunity is capable of producing disorders more frequently found in coeliac disease. Conditions secondary to GSE are important diagnostic criteria for gluten sensitivity when there may be no obvious intestinal abnormality. Presentation of GSE is often the result of initial recognition of the secondary condition which in followup testing (ATA test, AGA test, HLA-DQ typing, and/or biopsy) recognizes the primary condition. The secondary conditions associated with GSE tend to make late onset coeliac disease a systemic phenomena.

Main article: Associated Conditions

[edit] Idiopathic gluten sensitivity

Idiopathic gluten sensitivities are not as well defined as GSE or allergy. The debate over this subset stems from the fact that identification of all grades of GSE and allergies is not uniformly approached. Most cases of early GSE go undetected, particularly before 2005. There appears to be a small fraction of non-GSE gluten-sensitive individuals that show neither gluten-allergies but do have elevated anti-gliadin IgA or IgG. Common symptoms are peripheral neuropathies and cerebral ataxia. Within the GSE set these may be explained by calcification of brain channels and avitaminosis. Within the 'true' IGS, close examination has not been done. Given that this cohort of GS is idiopathic, the role of allergies, other sensitivies (e.g. aspirin), or other factors in IGS is also unresolved. Recent work with GSE indicate that gluten has an enhanced ability to permeate the intestinal epithelia and stimulate immune cells to divide independently of gliadin sequence which triggers T-cell simulation. This may be the course of gluten-sensitivity in individuals who are sensitive but do not have DQ2 or DQ8. Two studies inidicate a possible link between DQ1 and GS idiopathic neuropathies.

Silent Disease. Depending on testing somewhere between 3 and 15% of the normal population have anti-gliadin antibodies (AGA). Studies using anti-gliadin antibodies (AGA) reveal that in undiagnosed or untreated individuals with AGA, with increasing risk for lymphoid cancers and decreased risk for other associated with affluence.[16] Though it is unknown in these studies the percentage that are GSE.

[edit] IGS Neuropathies

Main article: Gluten-sensitive idiopathic neuropathies

Multiple sclerosis. Significantly increased levels of IgA and IgG antibodies against gliadin and gluten were found in multiple sclerosis compared with controls. IgA antibodies against casein were significantly increased. Anti-endomycium and anti-transglutaminase antibodies were negative.[17]

[edit] Autism

Further information: Autism diets and Autism supplements

In the early 1990s it was hypothesized that autism can be caused or aggravated by opioid peptides that are metabolic products of gluten.[18] Several treatments based on this hypothesis are widely promoted.[19] Popular diets eliminate foods containing gluten, often in combination with casein; studies supporting these diets have had significant flaws, so the data are inadequate to guide autism treatment recommendations.[20] Popular supplements include high dose pyridoxine (vitamin B6) and magnesium (HPDM),[21][22] dimethylglycine (DMG),[21][23] vitamin C,[23] polyunsaturated fatty acids (PUFA) such as omega-3 or omega-6 fatty acids, folic acid, and zinc. Few of these supplements are supported by scientific data; most have relatively mild side effects.[21][23]

[edit] IGS Non-neurological conditions

Oral Ulcerations. Antibodies to α-gliadin have been significantly increased non-coeliacs individuals with oral ulceration.[24] Anti-α-gliadin antibodies are freqeuntly found in patients with coeliac disease, to a lesser degree subclinical CD, but are also found in a subset who do not have the disease. The 1991 reference comes from a period when testing for subclinical CD was undeveloped.

Ocular exfoliations. Of people with pseudo-exfoliation syndrome, 25% showed increased levels of anti-gliadin IgA.[25]

Sjögren's syndrome, primary(pSS). 1/4th of patients with Sjögren's syndrome had responses to gluten, of 5 that had positive response to gluten, only one could be confirmed as CD and another was potentially GSE, the remaining 3 appear to be gluten-sensitive. All were HLA-DQ2 and/or DQ8-positive.[26]

Crohn's disease. Treatment to produce remission of Crohns disease symptoms on elimination diet indicated the most important foods provoking symptoms were wheat and dairy.[27]. A later paper showed little IgE mediated response to the except to dairy,[28] while another paper showed no significant anti-food IgE association.[29] Crohn's disease (CrD) may have a link to wheat that is independent of gluten. CrD appears to be associated with high anti-yeast antibodies (ASCA - yeast antigens that are found in bread and other cereal derived products) and affected individuals lack lectin binding proteins such that the Mannans in yeast and the antibodies that bind them aggravate colitis.

[edit] Gluten-allergy related sensitivities

Why treat gluten allergies as sensitivities? Over the last 10 years is has become apparent that allergies to certain substances do not behave in predictable ways. One clear example of this is exercise induced anaphylaxis and asthma, WDEIA (Wheat Dependent Exercise Induced Anaphylaxis) is now believed to be induced by ingested gluten that finds a way into the blood stream. This pathway is now believed responsible for some forms of eczema. Allergy tests may not reveal allergies to gluten because the unfractionated allergens are 'hidden' from these tests, and most currently available tests cannot detect these new allergens. Finally, allergies typically involve IgE, but some studies indicate there are several classes of responses, for example IgG1,IgG2, IgG4 that are associated with IgE.[30] Gluten allergy may be a cause of some idiopathic gluten sensitivity and gluten allergy can be a secondary consequence of gluten-sensitive enteropathy.

Main article: Wheat allergy

[edit] Comparative pathophysiology

Comparison of different forms of gluten sensitivity
Gluten-sensitive enteropathy Wheat allergy Gluten-sensitive idiopathic neuropathy
Typical symptoms steatorrhoea, malnutrition, diarrhea, lactose intolerance, food allergies Eczema, Asthma ataxia, peripheral neuropathies
Primary tissue targets Small intestine (epi) dermis, bronchi, intestines CNS, Peripheral nerves
Atypical pathologies Autoimmune diseases, chronic constipation, neuropathies, cancer (lymphoid) arthritis, migraines, anaphylaxis (exercise or aspirin induced) unknown
Secondary targets (common) blood (chemistry), bowel, nervous system, autoantigens connective tissue, CNS, vascular
Immunoglobin isotype IgA, IgG IgE, IgG, IgA IgG, IgA
Antibody recognition α/β,γ-gliadin (AGA), transglutaminase (ATA) albumins, globulins, Prolamins (ω-gliadin), glutelins α/β-gliadin
HLAassociations DQ2.5, DQ8, DQ2.2/DQ7.5 unknown DQ2, DQ8?, DQ1?
Cellular immunity T-cells, Eosinophils, Monocytes Mast cells, Eosinophils
Background & references Coeliac disease, GSEA conditions Wheat allergy IGS Neuropathies

Notes on table. Features of idiopathic neuropathy assume that all GSE cohort has been removed, assuming there is a gluten-sensitive, but not GSE contingent. Anti-gliadin antibodies covers all immunoglobulin isotypes and all gliadin isoforms. T-cell, Killer cell, and other gluten recognitions are covered in Gluten immunochemistry.

[edit] Immunochemistry of glutens

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The immunochemistry of Triticeae glutens is important in several inflammatory diseases. It can be subdivided into innate responses (direct stimulation of immune system), class II mediated presentation (HLA DQ), class I meditiated stimulation of killer cells, and antibody recognition. The responses to gluten proteins and polypeptide regions differs according to the type of gluten sensitivity. The response is also dependent on the genetic makeup of the human leukocyte antigen genes. In gluten sensitive enteropathy, there are 4 types of recognition, innate immunity (a form of cellular immunity priming), HLA-DQ, and antibody recognition of gliadin and transglutaminase. With idiopathic gluten sensitivity only antibody recognition to gliadin has been resolved. In wheat allergy, the response pathways are mediated through IgE against other wheat proteins and other forms of gliadin.

Innate immunity to gluten refers to a response initiator that works independently of T-cell receptor or antibody recognition of the innate peptide. This peptide acts directly on cells, such as monocytes, stimulating their growth and differentiation. The innate response peptide is found in a least 2 gliadins, α-2 and α-9 gliadin 31-43. [31] Innate immunity to this peptide is involved in coeliac disease, dermatitis herpetiformis and possibly juvenile diabetes.

HLA class I restrictions to gliadin are not well characterized. HLA-A2 presentation has been investigated. The HLA-A antigens can mediate apoptosis in autoimmune disease and HLA A*0201 in with the HLA-DQ8 haplotypes has been documented[32]. The class I sites were found on the carboxyl end of gliadin at positions 123-131, 144-152, and 172-180. The involvement of class I responses may be minor, since antibodies to transglutaminase correlate with pathogenesis and recognition of extracellular matrix and cell surface transglutaminase can explain the destruction within coeliac disease. This process involves antibody-dependent cellular cytotoxicity

[edit] HLA-DQ recognition of gluten

HLA-DQ proteins present polypeptide regions of proteins of about 9 amino acids and larger in size (10 to 14 residues in involved in binding is common for gliadin).[33] Each gluten protein is generally composed of repeated motifs. HLA-DQ can recognize a motif, and therefore HLA-DQ can recognize many motifs on each gliadin[34]. Numbers of different proteins from the grass tribe Triticeae have been found to carry motifs presented by HLA DQ2.5 and DQ8. Wheat has a large number of these proteins because its genome contains chromosomes derived from two goat grass species and a primitive wheat species.[35][36] The positions of these motifs in different species, strains and isoforms may vary because of insertions and deletions in sequence, different sized 'leader-sequence' that is removed after translation. There are a large number of wheat variants, and a large number of gliadins in each variant, and thus many potential sites. These sites once identified can be surveyed by sequence homology searches.

[edit] HLA-DQ2

HLA-DQ recognition of gliadin is critical to the pathogenesis of gluten senstitive enteropathy, it also appears to be involved in idiopathic gluten sensitivity. HLA-DQ recognition is mediated through CD4+ (mostly T-helper cells) as HLA-DQ on antigen presenting cells with gliadin peptides in the binding pocket stimulat the growth of CD4+ T-helper cells. This stimulates the expansion of B-cells lines that recognize the same regions of gliadin. HLA-DQ2 primarily presents pathogenic gliadins with the HLA-DQ isoform DQ2.5 (DQ alpha-5,beta-2) which is encoded by the DQ2.5 'cis' haplotype. The DQ2.2/DQ7.5 phenotype can also produce the DQ2.5 isoform. DQA1*0202:DQB1*0201 homozygotes (DQ alpha-2,beta-2) also appear to be able to present pathogenic gliadin peptides.

Numbers of different proteins from the grass tribe Triticeae have been found to carry motifs presented by HLA DQ2.5. Some of the T-cell sites have been identified. Many of these motifs are substrates for tissue transglutaminase and therefore can be modified by de-amidation (replacement of the -NH2 on glutamine with an -OH, creating glutamate) in the gut to create more immunoreactive peptides. The most important recognition appears to be directed toward the α-/β-gliadins. An example of the repetition of a motif across many proteins, the α-2 gliadin (57-68) and (62-75) are also found on α-4, α-9 gliadin. Alpha 9 gliadin has four T-cell sites (57-68), (62-75), (69-79) and (76-83) that overlap. [37] and α-2 gliadin also a similar site which resists proteolysis and composes a super site (56-88) of 33 amino acids. [38] Alpha-2 secalin, the glutinous protein in rye, is composed of two amino-terminal overlapping T-cell sites at positions (8-19) and (13-23).[37] Many gliadins contain the "α-20 motif", which is found in wheat and other Triticeae genera.(see also: "α-20" gliadin motifs). Recent papers on gliadin indicate that the "33mer" found suffices to maintain celiac disease together with the 19mer may suffice with other factors in triggering celiac disease. Detection of relative pathogenicity in the Poceae grass family of is focused on this site and homologs.

Gamma gliadin also contains repetitive DQ2 restricted T-cell sites, γ-giadin 60-79, 66-78, 102-113, 115-123 and 228-236[39] Gamma-M369999 gliadin contains 8 T-cell recognition sites, and γ-secalin has 2 T-cell sites (80-93), (117-125)[37]. Many γ-gliadins contains the "γ-30" motif (see also: "γ-30" gliadin motifs). The gamma-gliadin of wheat is believed to have a structure most conserved relative to ancestral gliadins. Barley, which is the most distantly related cereal to wheat in Triticeae has one similar T-cell site in its glutinous protein, hordein, (56-69) [37].

There are a few Triticeae glutelins presented by DQ2. In wheat, the low molecular weight glutenins often share structural similarity with the prolamins of the similar species of Triticeae. Two motifs, K1-like (46-60), pGH3-like (41-59) and GF1(33-51) have been identified. High molecular weight glutenin has also been identified as a potentially toxic region[40] (not yet characterized to the epitope level)

[edit] HLA-DQ8

There are a smaller number of gliadin (prolamin) peptides presented by HLA-DQ8. DQ8 (almost always DQ8.1 - DQA1*0301:DQB1*0302 haplotype) restrictions to gliadin typically develop against the carboxyl terminal of the protein, positions (~230-240) and (>241-<255) AJ133612. For γ-gliadins, γ-M369999 gliadin, reaction occurs at multiple sites (position: (~16-24), (>41-<60), (~79-90), (~94-102), (>101-<120)). DQ8 responses to the high molecular weight glutenin may be more important with DQ8 mediated celiac disease.[40]

[edit] Antibody recognition

Antibody recognition of gluten is complex. Direct binding to gluten such as anti-gliadin antibodies has an ambiguous pathogenesis in coeliac disease. The crosslinking of gliadin with tissue transglutaminase leads to the production of anti-transglutaminase antibodies, but this is mediated through T-cell recognition of gliadin. The allergic recognition of gliadin by mast cells, eosinophiles in the presence of IgE has notable direct consequences, such as exercise-induced anaphylaxis.

Anti-gliadin antibodies, like those detected in celiac disease bind to the alpha-2 gliadin at amino-acid positions 57-73 (57-73).[41] There has been some suggestion wheat plays a role in juvenile diabetes as antibodies to the non-glutinous seed storage glb-1 (a globulin) are implicated in crossreactive autoantigenic antibodies that destroy islet cells in the pancreas.[42] Anti-gliadin antibodies have been found to synapsin I[43] Omega-gliadin and the HMW Glutenin subunit antibodies have been found most commonly in individuals with exercise induced anaphylaxis and Baker's allergy, and represent a potent class of gluten allergens. Non-glutinous proteins in wheat are also allergens, these include: LTP (albumin/globulin), thioredoxin-hB, and wheat flour peroxidase.[44][45][46][47] A particular 5 residue peptide, Gln-Gln-Gln-Pro-Pro motif, has been found to be a major wheat allergen. [48]

[edit] Taming Triticeae Immunochemistry

New immunogenic motifs appear in the literature almost monthly and new gliadin and Triticeae protein sequences appear that contain these motifs. The HLA DQ2.5 restricted peptide "I I Q P Q Q P A Q" produced approximately 50 hits of identical sequences in NCBI-Blast search is one of a several dozen known motifs[37] whereas only a small fraction of Triticeae gluten variants have been examined. For this reason the immunochemisty is best discussed at the level of Triticeae, because it is clear that the special immunological properties of the proteins appear to have basal affinities to this taxa, appearing concentrated in wheat as a result of its three various genomes. Some current studies claim that removing the toxicity of gliadins from wheat as plausbile,[49] but, as the above illustrates, the problem is monumental. There are many gluten proteins, 3 genomes with many genes each for alpha, gamma, and omega gliadins. For each motif many genome-loci are present, and there are many motifs, some still not known. Different strains of triticeae exist for different industrial applications; durum for pasta and food pastes, 2 types of barley for beer, bread wheats used in different areas with different growing conditions. Replacing these motifs is not a plausible task since a contamination of 0.02% wheat in a GF diet is considered to be pathogenic and would require replacing motifs in all known regional varieties, potentially 1000s of genetic modifications.[49] Class I and Antibody responses are downstream of Class II recognition and are of little remedial value in change. The innate response peptide could be a silver bullet, assuming there is only one of these per protein and only a few genome loci with the protein. The bigger question is why late onset gluten sensitivity rapidly rising, is this truly a wheat problem or is it something that being done to wheat, or to those who are eating wheat (for example communicable diseases as trigger)? Some individuals are susceptible by genetics (early onset), but many late onset cases could have variable triggers because there is nothing genetically that separates the 30 to 40% of caucasians that could have Triticeae senstivity from the ~1% that, in their lifetime, will have some level of this disease. Another strategy in making wheat less immunogenic is to insert proteolytic sites in the longer motifs (25-mer and 33-mer) facilitating more complete digestion.

[edit] Gluten sources

From the perspective of gluten sensitivity there is no single definition of gluten that concisely defines all potentially pathogenic glutens. With wheat allergies, there can be a wide spectrum of species that may trigger allergies with similar proteins, the omega-gliadin proteins have similar proteins found in oats at high frequency, but omega-gliadin allergy is not a predictor of oat allergy or intolerance.[50] A person can have an allergy to wheat, but not rye.[51] Glutelins have not been characterized over broad taxa. With idiopathic gluten sensitivity, the antibodies that correlate with disease are anti-gliadin antibodies. Whether these antibodies are pathogenic or are simply indicators of circulating gliadin is unknown. For gluten-sensitive enteropathy, gliadin and homologous proteins from rye and barley cause disease. T-cell epitopes implicated in disease have been found in glutinous protein genes in all species sequenced within the tribe Triticeae.[52] Also, since barley is distantly related to wheat, but carries pathogenic epitopes it can be assumed that all members of Triticeae should carry T-cell sites capable of sustaining disease (see also Genetics of Triticeae). While often not explicitly stated in some standards, pathogenic glutens found in wheat are also found in Spelt and Kamut®(both types of wheat), Triticale (a trans-species Triticeae hybrid).

[edit] The oat controversy

Oats are a species within the grass tribe Aveneae which is in the Pooideae subfamily along with Triticeae (contains wheat, rye, barley and many other genera). Oats are the most closely related cereal species to Triticeae cereals. Oats may contain pathogenic proteins that sustain gluten-sensitive disease. Alternatively, oat seeds appear similar to seeds of wheat, barley and rye and cross-contamination between these grains is harder to detect. Wheat, barley and sometimes rye are common contaminants in oats.[53][54] Until this was investigated, oats were generally considered to be toxic to celiacs.[55] As a consequence, the current international standard for the "Gluten-free" designation, drafted in 1981 and agreed on in 1983[56] within the Codex Alimentarius (CA), states:

For the purpose of this standard, gluten is defined as those proteins, commonly found in wheat, triticale, rye, barley or oats to which some persons are intolerant.[57]

While the problem of contamination has been known for several years, a study published in June 2008 found that of 109 sources of oats screened, 85 had unacceptable levels of gluten from wheat, barley or rye.[58] Triticeae contaminated oats in the study came from many countries indicating that most sources of oats are unacceptable for GS based on contamination. The American Dietetic Association’s Nutrition Care Manual position on the use of oats in a medically neccesitated gluten-free diet is:

However, commercially available oats in the United States may be contaminated with small amounts of wheat, barley, or rye. For this reason, if you are newly diagnosed with celiac disease, you should not eat oats. Once your intestine heals, you may want to discuss the use of oats with your dietitian and physician.[54]

indicating the need for a separate standard of purity for people with gluten sensitivity.

[edit] New standards

 This article or section contains information about scheduled or expected future events.
It may contain tentative information; the content may change as the event approaches and more information becomes available.

Codex Alimentarius is undergoing revision and a revised standard will be presented at the meeting of the Codex alimentarius commision at the end of June. The proposed standard states:

"The Committee endorsed the labelling provisions as proposed.", and as part that provision "The Committee agreed to specify that the allowance of oats that are not contaminated with wheat, rye or barley in foods covered by the standard may be determined at national level.".[59]

In realizing the benefit of whole oats in a gluten free diet, the Canadian Celiac Association sought to assure oats and oat products fulfill the gluten-free standards set by the Canadian Food Inspection Agency and Health Canada:

in consultation with Health Canada, Agriculture & Agri-Food Canada and the Canadian Food Inspection Agency, has established requirements for growing, processing, and purity testing and labelling of pure oats.[60]

The proposed Codex Alimentarius revision goes onto to limit the amount of contaminant in oats that would qualify that product as gluten-free:

Gluten-free foods are dietary foods a) consisting of or made only from one or more ingredients which do not contain wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats[61] or their crossbred varieties, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer, and/or b) consisting of one or more ingredients from wheat (i.e., all Triticum species, such as durum wheat, spelt, and kamut), rye, barley, oats[61] or their crossbred varieties, which have been specially processed to remove gluten, and the gluten level does not exceed 20 mg/kg in total, based on the food as sold or distributed to the consumer.[59]

translating into 20 parts per million (PPM). In summary, oats can be tolerated in a gluten-free diet, but oat products should be limited in contamination from Triticeae derived gluten to 20 PPM. States are free to deny the GF-label standard for oat products, if warranted.

[edit] Gluten-free testing

The new standards, in part, came about because of new sensitive and specific testing procedures.[59] These procedures are capable of detecting wheat or multiple cereals at concentrations as low as 1 part per million (PPM or 1 mg/kg). A new barley-sensitive ELISA called the R5 sandwich assay does not detect gluten in any of 25 pure oat varieties, but it does detect barley, wheat and rye.[58] Another monoclonal antibody that targets the pathogenic "33mer" of α-gliadin shows a low level of crossreactivity with oats, though contamination may be an issue in this study.[62][63] These kits are capable of detecting and discriminating sources of contamination of oats, and can be supplimented with genetic tests, such a species specific PCR. Disease-sensitive farming practices, antibody testing and species specific genetic testing are capable of producing pure oats.[58] In the United States, 3 domestic GF-brands are available and one brand imported from Ireland 'reckons' to be 99.95% pure oats.[64][65] Two brands in the United States use the R5 antibody test and claim to be below 20 PPM in defined gluten. [64][66]

[edit] Oat-sensitivity

Some coeliacs respond adversely to oats. The associated genetics indicates they are at risk for EATL therefore eating oats without a some clinical surveillance increases the risk prolamin-insensitive refractory disease. Refractory disease found in DQ2 homozygotes is difficult to treat (See GSE associated cancers).

Main article: Oat sensitivity

[edit] Diets

Gluten-free dieting needs to be separated from gluten-sensitivity. The gluten free diet has become increasingly popular, and wheat-free aspects have become popular parts of other diets, such as the A-B-O diet. Excepting gluten allergies, most people who require a gluten-free diet are genetically predisposed by the HLA-DQ genetics, and this has nothing to do with the A-B-O genetics.

Since bleached wheat flour is a major source of fast carbs in western societies many improvements may be seen with wheat product reduction, but starch (polysaccharide) is not a gluten (protein) and does not cause a protein mediated immune response. Gluten sensitivity differs from diseases of affluence that are largely mediated by excess simple sugars, starches and saturated fats in the diet in that the primary targets of GSE are proteins,(prolamins and glutelins of the grass tribe Triticeae, and in some allergic sensitivities albumins and globulins). Wheat is more so dangerous because it has an enriched level of glutens derived from three ancestral species of wheat or goat grasses. Gluten-sensitive individuals must avoid these glutens, and in the case of coeliac disease the tolerance of gluten can be as low as 1 milligram of gliadin per week.

Gluten-free oats in a gluten-free diet. Gluten-free oats can provide a valuable source of fiber, vitamin B, iron, zinc and complex carbohydrates.[67] Recent studies show that gluten-sensitive individuals on a gluten-free diet often get too much simple starch, too little fiber and vitamin B. Currently most guidelines do not include oats in a gluten-free diet. While this is likely to change, oats are not recommended within a year of diagnosis because of the oat-sensitivity risk and complexity of the contamination issue. Consuming oats when anti-gliadin antibodies or gliadin are present increases anti-avenin antibodies, and may promote oat-sensitivity. Duodenal biopsy may be recommended after oat consumption is initiated. Since it is recommended that newly diagnosed celiacs seek the help of a dietician the inclusion of oats should follow consultation.

[edit] See also

[edit] References

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  3. ^ Wills AJ, Unsworth DJ (2002). "The neurology of gluten sensitivity: separating the wheat from the chaff". Curr. Opin. Neurol. 15 (5): 519–23. PMID 12351994. 
  4. ^ Ventura A, Bouquet F, Sartorelli C, Barbi E, Torre G, Tommasini G (1991). "Coeliac disease, folic acid deficiency and epilepsy with cerebral calcifications". Acta paediatrica Scandinavica 80 (5): 559–62. PMID 1908173. 
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  6. ^ Heading RC, Paterson WD, McClelland DB, Barnetson RS, Murray MS (1976). "Clinical response of dermatitis herpetiformis skin lesions to a gluten-free diet". Br. J. Dermatol. 94 (5): 509–14. PMID 773406. 
  7. ^ Volta U, De Giorgio R, Granito A, et al (2006). "Anti-ganglioside antibodies in coeliac disease with neurological disorders". Digestive and liver disease : official journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver 38 (3): 183–7. doi:10.1016/j.dld.2005.11.013. PMID 16458087. 
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