Triticeae glutens

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'Triticeae Glutens' are elastic, glue capable proteins derived from seed grasses. Seed Glutens of non-Triticeae plants have varieties of similar properties, but none singly can perform on a par with those of the Triticeae taxa, particularly the triticum species (bread wheat, durum wheat, etc). Triticeae proteins fall into four groups^[1]:

• albumins - soluble in hypotonic solutions and are coagulated by heat
• globulins - soluble on 'isotonic' solutions
• prolamins - alcohol in aqueous alcohol
• glutelins - are soluble in dilute acid or bases, detergents, choatrophic or reducing agents.

Nomenclature - Proteins of the Triticeae endosperm that are generally rich in arginine, proline, glutamine, and/or asparagine.

• Prolamins
  • Triticum (True Wheats) - gliadins
  • Hordeum (Food Barleys) - hordeins (B-hordein is homolous to LMW-glutenin)
  • Secale (Food Ryes) - secalins
• glutelins
  • Triticum - glutenin
  • Hordeum - barley glutelin
  • Secale - rye glutelin

Contents 1 Triticeae Gluten Genetics 2 Biochemistry of "Triticeae" Prolamins and Glutelins 2.1 Chemical Behavior 2.2 As Substrates for Enzymes 3 Immunochemistry of Triticeae glutens 4 Triticeae Glutens and Industry 5 Triticeae and Human Disease 5.1 Coeliac Disease and Triticeae 5.2 Type 1 Diabetes and Triticeae 5.3 In Misc. Autoimmune & Secondary Conditions 5.4 Exercise-Induced Anaphylaxis and Baker's Allergy 6 References

[edit] Triticeae Gluten Genetics

Wheat has three genomes (AABBDD) and it can encode for many variations of the same protein, even in the gliadin subcategories many types of gliadin per cultivar, X = genome (A, B, or D genome chromosomes (1 to 7)))

• Glutenins and Gliadins on Chromosome 1, short arm
  • ω-gliadin - (Gli-X1 - A is null @ 84%, B (>8 alleles), D (>4 alleles))
  • glutenin, LMW - (Glu-X3 - A (>5 alleles), B (>7 alleles), D (>2 alleles))
  • γ-gliadins, most - (Gli-X3), homologous proteins exists in Barley.
  • β-gliadins, few - variants of γ-gliadin that migrate with β-gliadins?
• long arm (Chromosome 1)
  • glutenin, HMW (Glu-X1 - A (>2 alleles), B (>8 alleles), D (>4 alleles))

• Gliadins on Chromosome 6 (A, B and D genomes) short arm (~30 coding loci over A, B,D undeterminant alleles)
  • α-gliadin - (Gli-X2)
  • β-gliadins, most - (Gli-X2) variants of α-gliadin with alter isoelectric points.
  • γ-gliadins, few - (Gli-X2) variants of α-gliadin that migrate with γ-gliadins?

[edit] Biochemistry of "Triticeae" Prolamins and Glutelins

[edit] Chemical Behavior

• Gliadins, as an example of the prolamins, in Triticeae. gliadins are separated on the basis of electrophoretic mobility and isolelectric focusing.
  • α-/β-gliadins - soluble in low percentage alcohols.
  • γ-gliadins - ancenstral form of cysteine rich gliadin with only intrachain disulfide
  • ω-gliadins - soluble in higher percentages, 30% - 50% acidic acetonitrile.

• Cultivar Glutenins in Triticeae
  • 35-40% of wheat protein.
  • In wheat forms long covelantly interlinked polymers of two repeating subunits.
    • High Molecular Weight (HMW) - proline-less (Glu-1 locus)
    • Low Molecular Weight (LMW) - α-gliadin-like polypeptide (Glu-3 locus)
  • Barley has two glutelins, soluble at high pH, precipitates at low pH.
    • α-glutelin (major component, HMW) - cuts at 1 to 3% rel. saturation ammonium sulfate
    • β-glutelin (minor component) - cuts at 18% rel. saturation ammonium sulfate
  • Rye has one glutelin
    • HMW - (equivalent of Barley α-glutelin)
    • LMW - subspecies sylvestre has (Glu-R3) glutenin-like (Ssy1, Ssy2 and Ssy3 loci)^[2]

[edit] As Substrates for Enzymes

Modification of Glutamine
Gliadins and to a lessor degree glutelins are excellent substrates for deamidiation particularly by mammalian tissue transglutaminases (tTG). Deamidation is a process in which the R-C0-NH2 portion of glutamines (or asparagine) is hydrolyzed to R-CO-OH forming glutamic acid or aspartic acid. In glaidin the -QQP-, -QVP-, -QLP-, -QYP- tripeptides in the context of favorable adjacent peptides are readily deamidated.^[3] Most proteins have few or no such transglutaminase sites; however alpha gliadin has 13 such sites. Human tissue transglutaminase not only deamidates gliadin, but it also crosslinks itself to gliadin, which has immunological consequences. Gliadin also has a small peptide that appears to alter the distribution of transglutaminase in the gut but is not crosslinked, the mechanism of its 'innate' behavior is not clear. tTG also crosslinks gliadin to other proteins via these sites, generating anti-food responses, anti-self protein responses, and self-crossreactive responses to food proteins that result in secondary autoimmunities. The role of tTG in the extracellular matrix is to crosslink lysine side chains of proteins such as collagen to matrix proteins, however glutens appear to infiltrate in small intestinal pathogenesis and interfere with this process, resulting in a false immune recognition of the matrix and surrounding cells as invaders, leading ultimately to the descruction of the intestinal mucousa. It is possible that the innate response and cellular immunity are elicitied as defensive response of 'triticeae glutens to overconsumption of seeds.

Proteolysis
While prolamins and glutelins are excellent deamindase and transamidase substrates the highly repetitive motives, particularly polyproline/glutamine tracts are often poor substrates for gastroentestinal endoproteases, such as those produced in the GI tract. One clear example is a 33-mer of α-2 gliadin. This is one of the ironic properties of wheat, since a major advantage of wheat is the amount of protein in the wheat, however, some of this is wasted to the gut flora (or host immune system) since it cannot be broken down. One suggested remedy to this problem are new enzymes that help specifically break prolamins in the stomach. This may prevent the onset of wheat related disease in susceptible individuals, but no such screening is currently effective and once the clinical state is reached most individuals are so sensitive to wheat gliadins that, effectively, complete digestion in the stomach would be required.

[edit] Immunochemistry of Triticeae glutens

The immunochemistry of Triticeae is important in several autoimmune diseases (see section on Human Disease). 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. Numbers in parenthese (###-###) refer to amino acid sequences in the proteins that are immunogenic by the stated categories (Innate, Antibody epitopes, HLA Class II epitopes, HLA Class I epitopes).

• Innate immunity
  • α-/β-gliadins
    • α-2 gliadin (31-43)^[4]
    • α-9 gliadin (31-43))^[4]

• HLA class II Restrictions of CD4+ T-lymphocytes (Anti-gluten response mediators)
  • DQ2.5 (DQA1*0501:DQB1*0201) and DQ2.2/DQ7.55 (DQA1*0201:DQB1*0202/DQA1*0505:DQB1*0301)
    • α-/β-gliadins (amino, central and carboxyl ends)
      • α-2 gliadin (57-68), (62-75),^[5] (56-88, the 33mer)^[6]
      • α-4 gliadin (57-68), (62-75), (69-79)^[5]
      • α-9 gliadin (57-68), (62-75), (69-79), (76-83)^[5]
      • α-_ gliadin ' 'α-20' ' motif^[7] (mat. 76-86)¹, (88-98, mat +13)², (89-99, mat +13)³, (95-105, mat +20)⁴, (96-106, mat +20)⁵, (101-111, mat. +20)⁶,
        • ² _AAY45930 Aegilops speltoides (wild spelt, PMID 16403227)
        • ⁴ _ABD62749 Triticum monococcum (Einkorn, ABD62749), T. aruatu
        • ¹ _BAA12318, ... Triticum aestivum (common wheat, PMID 9738916)
        • ³ _AAY45923, ... Triticum monococcum (Einkorn, PMID 16403227)
        • ⁵ _AAA96525, ... Triticum aestivum (common wheat)
        • ⁵ _CAA10257 Triticum aestivum spelta arduini (spelt)
        • ⁵ _ABD62750 Triticum monococcum aegilopoides (wild einkorn)
        • ⁵ _ABB92633, ... Triticum turgidum durum (durum wheat)
        • ⁵ _ABB92633 Triticum turgidum monococcoides (wild emmers wheat)
        • ⁵ _AAY45941, ... Aegilops Tauschii (Tausch's goatgrass, PMID 16403227)
        • ⁶ _AAA34290 Triticum aestivum (PMID 3038689)
    • -α-2 secalin (8-19), (13-23)^[5]
    • γ-gliadins
      • γ-5 gliadin (60-79), (66-78), (102-113), (115-123), (228-236)^[8]
      • γ-M369999 gliadin (16-24), (65-76), (70-79), (79-90), (94-102), (115-126), (128-136), (233-241)^[8]
      • γ-_ gliadin ' 'γ-30' ' motif^[7]
        • _AAK84773- (207-215) Triticum aestivum cheyenne (bread wheat)
        • _AAK84777- (236-244) Triticum aestivum cheyenne (bread wheat)
        • _AF120267- (246-254) Triticum aestivum spelta Oberkulmer
        • _AAK84778 -(249-257) Triticum aestivum cheyenne (bread wheat)
        • _AAK84777 -(253-261) Triticum aestivum cheyenne
        • _AAF42989 - (259-267) Triticum aestivum Yamhill
        • _AAK84774-(278-286) Triticum aestivum cheyenne
        • _AAK84779- (288-296) Triticum aestivum cheyenne (bread wheat)
        • many more in the Aegilops, Triticum, Thinopyrum genera.
    • -γ- secalin (80-93), (117-125)^[5]
    • --- hordein (56-69)^[5]
    • w-gliadins
      • w-ABI20696 gliadin (T. timopheevii) (96-106)
      • w-5-gliadin
    • LMW glutenin
      • K1-like (46-60)
      • pGH3-like (41-59), GF1(33-51)
    • HMW glutenin -^[9] (not yet characterized to the epitope level)

• • DQ8 (DQA1*0301:DQB1*0302)
    • α-/β-gliadins (carboxyl end)
      • α-AJ133612 gliadin (~230-240), (>241-<255)
    • γ-gliadins
      • γ-M369999 gliadin (~16-24), (>41-<60), (~79-90), (~94-102), (>101-<120)
    • HMW glutenin^[9](higher then DQ2.5) - (not yet characterized to the epitope level)

• HLA Class I Restrictions of CD8+ T-lymphocytes (Apoptosis mediators)
  • A2 (A*0201 in DQ8+)^[10]
    • α-/β-gliadins (carboxyl end)
      • A-gliadin (123-131), (144-152), (172-180)

• Antibody recognition
  • α-/β-gliadins
    • A-2 gliadin Â(57-73)-IgA^[11]

Conclusions on Immunochemistry. For brevities sake the list was partially extended for alpha and gamma glaidins. The list above is far from complete, 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^[5] 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,^[12] 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.^[12] 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.

[edit] Triticeae Glutens and Industry

Glutens are an essential part of the modern food industry. The industry of wheat goes back to before the Neolithic period when people process grain berries (or corns) singley by hand. During the early phase of cultivation wheats were selected for their harvestability and growability under various climate conditions resulting in the first cultivars. This industry spread into many areas of western eurasia during neolithization, carrying the more primitive cultivars. These grains were capable of being used for soups (speltiods) or tediously ground into simple flours and baked goods. During the second phase an Emmers wheat was produced that was an alloquadraploid species and this contained more gluten making baking more efficient this also spread during the neolithization but in places such cultivars were a minority. One variant of emmer wheat is called durum wheat and is the source of semolina flour, used in making pastas and other food pastes. Comparable varieties are found through out Eurasia. Finally, emmers wheat was combined with a goat grass (Aegilops tauschii) to form allohexaploid bread wheat, which has a soft fine texture after rising and cooking. The industrial properties of this wheat are based in its glutens, glutens of high elasticity, high heat tolerance of other glutens or that change when subjected to heat to produce stronger polymers.

Comparing wheat gluten with corn (Zea) glutens.
Corn is prepared for breading by boiling in water with alkali, resulting in a de-skinned material called nixtamalized masa. Masa can be used for industrial purposes (tortillas, tamales, chips), but it must be used quickly because its glutens change rapidly and binding decreases rapidly. Masa does not store well and chemicals are added to enhance preservation at the expense of quality. At its peak attempting to use masa as dough generally results in a crumbly flat bread, correctable by regrinding masa to a fine flour and adding gums (such as Xanthan Gum) corn will never achieve the refined smoothness and silkiness of bread flour; however, there is a developing Gluten Free food industry that is developing corn flour composites for the purpose for wheat-flour replacement. Masa, of course, can be considered an industrial grain for other reasons, despites its shortcoming it can be combined with fat to make tamales (and wrapped in leaves for storage life of several days), or to make tortillas that wrapped other foods and packaged. While masa is suitable as a flatbread flour in rural communities within major cities were people cannot grind and prepare masa on a daily basis masa quickly falls out of favor in masa utilizing cultures and is replaced by wheat comparables like wheat flour tortillas.

Important Triticeae Composites
Wheat, however, has been far more exploited in history. When the flour is combined with water and yeast the dough can be risen and subsequently fixed by heat resulting in a hard outer shell with a soft palatable interior. This makes bread amicable for both transport and preserves the bread for several days (in dry conditions). Barley can be sprouted for a short period and roasted, the resulting malt can be ground for food or combined with bread yeast (currently a brewers variety) to produce beer and distilled spirits such as whiskey, vodka and sour dough malts. Adding mild acid to rye flour activates it for bread making (Sourdough breads used in northern Europe). Adding egg to T. durum semolina flour can be used to make pastas, or a variant used to make Chinese dumplings. Wheat or semolina flour can be added other ingredients such as fish, meat or milk to create food pastes. Wheat can be further processed to a very fine flour and sifted, alternatively the glutens either can be extracted and readded to other products. While many seed glutens and food gums when combined with food starch, come close to creating the refined products of wheat flour and durum flour, no combination can come close to the qualities of these flours at a comparable price.

Malting
Some triticeae cultivars, like barely, have relatively low protein values. This makes them more acceptable for brewing without wasting soil nutrients. Glutens in wheats are storage proteins that are designed to help the plant grow during its early life, and among the plant proteins are enzymes that convert starch to sugar. These proteins are activated during sprouting and the starch around the endosperm is converted to sugars, later the prolamins are broken down to provide the young seeds with a source of nitrogen and energy given triticeae seedling a great boost during early life.

Once the starch is converted to sugar it can be readily fermented by Saccharomyces cerevisiae however first the sprouting process should be stopped. In order to do this the partially sprouted grains are placed in a roasting oven and roasted until the sprouts are sterilized and dried, this process of sprouting and drying is called malting. Then the roasted sprouts are ground, rehydrated and fermented. This produces a crude beer. Evidence for beer industry has been found in the ancient Egyptians and some archaeologist believe that neolithization of northern Europe may have been preferential for barley as a result of its preferential capacity for fermentation.

Gluten Deamidation
The deamidation potential for wheats is discussed above. Glutens are generated by the wheat starch industry. Glutens however are more difficult to handle once starch and other proteins are removed, for example alcohol soluble glutens cannot be mixed with dairy since the alcohol denatures and precipitates dairy proteins. Therefore, gluten is often modified for commercial use by deamidation by treatment with acid at high temperatures, or enzymatic treatment with deamidase or transglutaminases. The increase charge increases the hydrophilicity of gliadins causing them to stretch out in solution. Deamidation of 20% of glutamine side chains to glutaminate suffices to generate a soluble product. This renders gluten soluble enough without alcohol to mix with other products like milk.

Gluten Sensitivity Reveals Unexpected Infiltration of Wheat into Foods
One of general problems of Triticeae glutens in their solubility (or lack thereof). The special chemical properties of glutens is discussed above. In addition certain regions of the prolamins are indigestible. These properties of the gliadins also make them excellent glues which are required for making refined pastas, food pastes, high quality baked goods and even pastes and paints for school children. As a result wheat glutens are creeping into foods and household products worldwide (and the labeling often does not 'catch-up') in an effort to make regional foods competitive in internal and international markets. Other products, such as soy sauces, wheat ferments are added a flavoring agent, and in many of these sauces the wheat flour exceeds soy flour in the starting materials. The wheat-free ' 'traditional style' ' alternatives are often very expensive. Extracted glutens are also added to foods for specific reasons; the sticky quality of glutens is exploited, for example, in production apparently wheat-free foods such a corn (zea) and potato chips, but have triticeae gluten added to during processing so that flavoring agents will stick to the product during and after processing. Since the unflavored products are processed on the same equipment as flavored products these products may variably have sufficient gluten to cause a reaction in sensitive individuals. Some of the most elusive examples of contamination come from the drug industries, that use triticeae sources in the manufacturing of medications, but because of the risk of infringement are often reluctant to disclose potential for gluten prolamin, glutelin, or globulin contamination. Unfortunately, for people with food allergies and intolerances the inadequate labeling, delayed announcement of gluten risks, of annuciation of the potential for episodice contamination or ' 'wheat creep' ' is not often evidenct in product labels.

Triticeae with Wheels
There are still other forms of ' 'wheat creep' ', the most notorious example that GSE sufferers are aware of is oats. Packagers of oats have identified the sources of wheat as uncleaned transport trucks and storage bins. Another source is free seeding wheat rye or barley in fields in which crops are rotated. So bad is the 'creep' of wheat in the western oat supply that science cannot absolutely descriminate whether oats mediate GSE or whether it is the wheat contaminants in oats that mediates CD. There has been a hefty argument in the literature over the purity of oats used in oat mediated GSE studies. In studies of children in Finland with GSE, the most severe and life threatening form, an a replacement diet including oats uncontaminated with Triticeae has been effective in treating GSE and thus it is likely that Triticeae contamination is the principle source of oat intolerance. However, this does not negate from the possibility that a small cohort of individuals elsewhere may be oat sensitive, or that specific strains of oats may develop inflammatory responses in some individuals.

These examples show how integral triticeae cultivars and their derivatives are to both ancient and modern societies, and the special properties of these cultivars is a primary factor in the westernization of societies based on other grain cultivars. The continued experimentation with triticeae promises to produce an infinite new products of human consumption and use. At the same time, it also becomes so integral to modern culture that its risks are often ignored. It is not clear, for instance, why late onset autoimmune enteropathy has risen to such a degree in modern times, and once diagnosed such patients have difficulty dealing with the pervasiveness of triticeae culture in all but the most undeveloped human societies.

[edit] Triticeae and Human Disease

Rather than have a section for each Triticeae cultivar, all known medical conditions linked to all cultivars are placed in this section. It is not clear for instance which pathogenic isoforms in bread wheat come from Aegilops, Crithodium, or Triticum, and similar proteins exist in barley and rye, paraphyletic to the bread wheat taxonomy (see Image below). If there are any sufficient divisions between these proteins in the Triticeae clad that might result in adequat substitution to modulate downward the conditionally pathogenic effects. From the standpoint of individual being treated on a wheat-free diet it is fair to assume all triticeae cultivars have these conditionally pathogenic proteins and this may include grass seeds of sister taxa.

[edit] Coeliac Disease and Triticeae

Cultivars of Triticeae can induced Gluten Sensitive Enteropathy (GSE) in susceptible individuals. The incidence rate is about 1:100 lifelong risk in most western populations and is one of the most common autoimmune diseases. While considered by some to be an allergic disease, the effects of wheat gliadin (α/β and γ), barley hordein and rye secalin (In some individuals glutenin or glutenin like proteins can play a role) act more as a poison which cause a destructive innate immunity^[4] and cellular immunity that flattens the epithelium of affected individuals and causes acute malabsorption. Gluten peptides, particularly when deamidated or transamidated alter the behavior of proteins, the most notorious is tissue transglutaminase (tTG), a protein involved in deamidation and transamidation of the glutamine amide. The response is Mediated by HLA DQ2.5(HLA DQA1*0501:B*0201) and HLA DQ8(HLA DQA1*0301:B1*0302). DQ2.5 is found at high frequency in West Africans, Sardinian, parts of Spain, Irish, Welsh, Cornish, British, Scottish, Norwegian, Swedish, Finnish, Danish, Northern Slavic, Hungarian, Serbian, Yugoslavian, Swiss, Canada, United States and accounts for the overwhelming majority of GSE incidences detected. DQ8 is globally distributed but is at very high frequency in indigeonous northern South Americans, Central Americans, Mexico, Sweden, Finland, Northern Russia, Japan, Korea and Bedoin and is less often associated with GSE, but heterozygotes of DQ2.5/DQ8 such as occur in Scandinavia are at elevated risk relative to homozygotes of either haplotype. GSE is very uncommon in countries where Triticeae is not a primary cultivar, even in susceptible populations, but is on the rise in countries with susceptible populations and growing wheat consumption, such as Japan and Latin America. Aside from Triticeae and DQ2.5 (and/or DQ8), other genetic risk factors are not clear, one CTLA4 gene product shows linkage to celiac disease but 33% more frequent in GSE than in non-GSE. Other risk factors such as chronic infection of GI tract by enterovirus, rotavirus may play a role, but GSE is known to have much higher risk in families than in the general DQ2.5 or DQ8 bearing population indicating complex genetic factors are involved.

[edit] Type 1 Diabetes and Triticeae

The incidence of Juvenile Type 1 Diabetes (T1D) is about 1:500 in the U.S. population, and is the result of autoimmune damage to the Islets of Langerhans cells in the pancrease. The level of adult onset T1D plus ambiguous T1D/T2D is unknown. It is unclear the how large a role Triticeae has in T1D which also shows stong linkage to DQ2.5 and DQ8. Childhood (male) Type 1 diabetes increases the risk for GSE and vice versa^[13] and it now appears that GSE precedes T1D in many cases^[14] and an active search for celiac disease in early juvenile diabetes patients revealed that GF diet resulted in some improvements.^[15] A high frequency of diabetes patients have antibodies to the GSE autoantigen, tTG^[16] along with increased levels of Gluten specific T-cells in T1D patients. From an evolutionary point of view it is difficult to explain the high association of T1D and DQ2.5 given negatively selective nature of the disease in NW European population given the number of studies suggesting that the "Super B8" haplotypes has been under positive selection, and appears to be the most characteristic HLA type in NW Europeans indicating an advanced natural history of the haplotype. A T. aesitivum storage globulin, Glb-1 (locus), was identified that is similar to the hypersensitizing peanut protein Ara h 1 and other known plant hypersensitizing proteins. Antibodies to this protein correlated with levels of lymphocyte infiltration into Islet regions of the pancrease.^[17] Gastrointestinal viruses may play a role.^[18][19][20]

[edit] In Misc. Autoimmune & Secondary Conditions

These conditions are consider idiopathic because their occurrence is unpredictable or have a random association with other diseases (above), particularly GSE. Triticeae glutens are the primary cause of dermatitis herpetiformis. Cross-reactive anti-beef-collagen antibodies may explain some rheumatoid arthritis (RA) incidences.^[21] Although the presence of anti-beef collagen antibodies does not necessarily lead to RA, the RA association with Triticeae consumption is secondary to GSE and involves DRB1*0401/4 linkages to DQ8^[22] and is debatable. Similar ambiguities with other conditions has resulted because the clinical manifestations of celiac incidences that fall below clinical detection can still promote secondary allergic responses and secondary autoimmune diseases. The frequency in western societies is typically around 1/2 to 1%, but the detection rate are typically 10-fold lower, however the association with other, secondary, diseases remains largely idiopathic. The course of clinical correlation between GSE and secondary diseases can take years and in some cases decades, if such correlations are made in the patients lifetime, such delays often result in irreversible conditions. One prime example is calcium channel obstruction in the brain and dementia. There is a growing body of evidence suggesting that subclinical cases in older adults will typically progress toward dementia or epilepsy, a large number of studies in Italy and Spain have documented these cases, though the autoimmune condition is not known, folic acid maladsorption may be the cause. Patients and physicians should be aware of the risk of a GSE correlation for most autoimmune diseases, although the correlation with some diseases can be almost insignificant (or so low in number its significance cannot yet be assessed). GSE and subclinical GSE are also responsible peripheral neuropathies, depression, chronic fatique syndrome, anemias, gastroesophageoal reflux disease (GERD) that are the indirect consequences of maladsorption of vitamins and essential fatty acids. GSE also elevates the risk for certain lymphomas (Enteropathy-Associated T-cell Lymphoma) and cancers of the intestinal tract approximately 5 fold; a risk that is irreversible and presses for the need for early detection and treatment.

[edit] Exercise-Induced Anaphylaxis and Baker's Allergy

Wheat gliadins and potentially oat avenins are associated with another disease, known as Wheat Dependent Exercise Induced Anaphylaxis (WDEIA) which is similar to Baker's Allergy as both are mediated by IgE responses.^[23] In EIA however the ω-gliadins^[24] and similar proteins in other Triticeae genera can be inhaled or enter the blood stream during exercise where they cause acute asthmatic or allergic reaction).^[25] . This response to ω-gliadins may stem from a time when the seed grasses of basal Triticeae taxa, as some species still do, produce seeds that get trapped in grazing animals (ear, eyes, nasal cavities) as a potential defense mechanism that also facilitates the seeds spread. One recent study of ω-gliadins demonstrated these gliadins are more similar to the bulk of oat avenins than α/β or γ gliadins but, so far, oat avenins have not been linked to EIA. The occurrence of both WDEIA and Baker's allergy are increased in GSE.

[edit] References