The team neutralized gliadin through complexation to a linear copolymer of hydroxyethylmethacrylate (HEMA) and sodium 4-styrene sulfonate (SS). They then examined the ability of the polymeric binder to mitigate the damaging effect of gliadin on cell-cell contact in IEC-6, Caco-2/15, and primary cultured differentiated enterocytes.

They used gliadin-sensitive HLA-HCD4/DQ8 transgenic mice to measure the effectiveness of the polymeric binder in averting gliadin-triggered intestinal barrier dysfunction.  They found that Poly(hydroxyethylmethacrylate-co-styrene sulfonate) [P(HEMA-co-SS)] complexed with gliadin in a fairly precise manner.

Exposing intestinal cells to gliadin caused major changes in both cell structure and cell to cell contacts. By complexing the gliadin with P(HEMA-co-SS) the researchers were able to prevent these undesirable changes. More importantly, the P(HEMA-co-SS) inhibited gliadin digestion by gastrointestinal enzymes, which minimized the development of peptides that trigger immune adverse immune reactions.

By co-administering P(HEMA-co-SS) with gliadin to HLA-HCD4/DQ8 mice, researchers were able to eliminate gliadin-triggered changes in the gut barrier and lower intraepithelial lymphocyte and macrophage cell counts.

From these results, the team concludes that polymeric binders can prevent in vitro gliadin-induced epithelial toxicity and intestinal barrier dysfunction in HCD4/DQ8 mice. Such polymeric binders might play a significant role in the treating people with gluten-induced disorders.

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A number of studies have shown that people with gluten sensitivity and intestinal inflammation, but just how great is the risk? However, of those previous studies that show an increased risk of death associated with the disease, many were not population-based, lacked children and outpatients, while others were hampered by small numbers of participants.

A team of Swedish researchers led by Jonas F. Ludvigsson, MD, PhD, of Sweden's Örebro University Hospital, recently set out to conduct a large-scale, population-based study regarding mortality risk levels for people with celiac disease, and also for those with "gluten intolerance."

Ludvigsson and colleagues examined histopathology data from tissue biopsies collected from 46,121 Swedish patients nationwide between July 1969 and February 2008. Of those patients, 29,096 had celiac disease, while 13,306 showed inflammation of the small intestine and 3,719 showed latent celiac disease, elevated blood antibodies used as markers for celiac disease, but no sign of gut inflammation or damage.

The researchers compared the patient data to records of the Swedish Total Population Register to calculate mortality rates for the three groups of patients. They found that among the patients there were 3,049 deaths among those with celiac disease, 2,967 deaths for those with inflammation, and 183 deaths for patients with latent celiac disease.

The overall risk was not great, mortality risk was 75% higher for patients with mild intestinal inflammation at a median follow-up of 7.2 years (95% CI 1.64 to 1.79), and 35% higher for patients with latent celiac disease, or gluten sensitivity, at median follow-up of 6.7 years (95% CI 1.14 to 1.58).

The study also revealed that people diagnosed with celiac disease faced a 30% greater risk of death at a median follow-up of 8.8 years (95% CI 1.33 to 1.45). That means that over the 8.8 years following the study, 30% more people with celiac disease died compared to the control group.

These findings confirm previous studies that show higher mortality rates in celiac patients. Major causes of death for people with celiac disease are cardiovascular disease and cancer.

Still, overall mortality risk associated with celiac disease and intestinal inflammation for gluten intolerance was small, with just 2.9 additional deaths per 1,000 person-years for people with celiac disease, and 10.8 and 1.7 additional deaths per 1,000 person-years for people with inflammation and latent celiac disease, respectively.

Of the population-based study, Jonas F. Ludvigsson, MD, PhD, of Örebro University Hospital in Sweden, and colleagues writes,
"we examined risk of death in celiac disease according to small-intestinal histopathology...Excess mortality was observed independent of histopathology, but absolute excess mortality risk was small, especially in children."

In an accompanying editorial, Peter H. R. Green, MD, of Columbia University Medical Center, writes that the study's findings on patients with latent celiac disease, those patients who, in the United States, would be labeled as having "gluten sensitivity," were the most intriguing.

Dr. Green writes that until recently, "gluten sensitivity has received little attention in the traditional medical literature, although there is increasing evidence for its presence in patients with various neurological disorders and psychiatric problems."

Furthermore, researchers currently know little about the long-term consequences of mild gut inflammation. In such cases, patients typically show no sign of villous atrophy,  the flattening of the innermost membrane of the intestinal wall common to people with clinical celiac disease.

Overall, the "risk of death among patients with celiac disease, inflammation, or latent celiac disease is modestly increased," the researchers concluded.

The researchers speculate that the increase in mortality might result from chronic inflammation that damages patients' small intestines (the duodenum, specifically) or from malnutrition that saps their vitamins and energy.

The researchers did not, however, rule out the possibility that mortality may be due to other existing conditions. They also cautioned that some patients with inflammation may have been misclassified as having latent celiac disease or partial villous atrophy, skewing mortality rates upward for the latent celiac disease group.

Green concludes that the "study by Ludvigsson and colleagues reinforces the importance of celiac disease as a diagnosis that should be sought by physicians. It also suggests that more attention should be given to the lesser degrees of intestinal inflammation and gluten sensitivity."

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The situation might be likened to sailors who've an island, but not explored it. Researchers knew Zonulin existed, and some of its influences, but little else about it. Recently, a team of scientists led by Alessio Fasano, M.D., set out to isolate and decode zonulin. Their results are in, and Fasano's research team has successfully identified zonulin as a molecule called haptoglobin 2 precursor.

Understanding the exact biochemistry of zonulin, the exact make-up of the protein molecule, is crucial to a comprehensive study of zonulin and its relationship to numerous inflammatory disorders.

Dr. Fasano is a professor of pediatrics, medicine and physiology and director of the Mucosal Biology Research Center and the Center for Celiac Research at the University of Maryland School of Medicine.

Haptoglobin is a molecule that has been known to scientists for many years. It was identified as a marker of inflammation in the body. Haptoglobin 1 is the original form of the haptoglobin molecule, and scientists believe it evolved 800 million years ago. Haptoglobin 2 is a version found only in humans. Scientists believe the mutation occurred in India about 2 million years ago, spreading gradually among increasing numbers of people throughout the world.

Dr. Fasano's study showed that zonulin is the precursor molecule for haptoglobin 2 — that is, it is an immature molecule that develops into haptoglobin 2. Scientists previously believed that such precursor molecules played no role in the body other than to develop into the molecules they were destined to become.

But Dr. Fasano's study reveals precursor haptoglobin 2 as the first precursor molecule to serve another function altogether; that of opening a gateway in the gut, permitting gluten to pass through. People with celiac disease suffer from a sensitivity to gluten.

"While apes, monkeys and chimpanzees do not have haptoglobin 2, 80 percent of human beings have it," says Dr. Fasano. "Apes, monkeys and chimpanzees rarely develop autoimmune disorders. Human beings suffer from more than 70 different kinds of such conditions. We believe the presence of this pre-haptoglobin 2 is responsible for this difference between species."

According to Dr. Fasano, the haptoglobin 2 molecule "could be a critical missing piece of the puzzle to lead to a treatment for celiac disease, other autoimmune disorders and allergies and even cancer, all of which are related to an exaggerated production of zonulin/pre-haptoglobin 2 and to the loss of the protective barrier of cells lining the gut and other areas of the body, like the blood brain barrier."

"The only current treatment for celiac disease is cutting gluten from the diet, but we have confidence Dr. Fasano's work will someday bring further relief to these patients. Zonulin, with its functions in health and disease as outlined in Dr. Fasano's paper, could be the molecule of the century," says E. Albert Reece, M.D., Ph.D., M.B.A., dean of the School of Medicine, vice president for medical affairs of the University of Maryland and John Z. and Akiko K. Bowers Distinguished Professor.

Dr. Fasano published his findings in the online version of the Proceedings of the National Academy of Sciences, appearing the week of September 7, 2009.

A team of researchers recently set out to determine whether oral administration of LL-delivered DQ8-specific gliadin epitope induces Ag-specific tolerance.

The research team was made up of Inge L. Huibregtse, Eric V. Marietta, Shadi Rashtak, Frits Koning, Pieter Rottiers, Chella S. David; Sander J. H. van Deventer, and Joseph A. Murray under the auspices of the Center for Experimental and Molecular Medicine of the Academic Medical Center of the University of Amsterdam in the Netherlands.

Celiac disease is associated with either HLA-DQ2- or HLA-DQ8-restricted responses to specific antigenic epitopes of gliadin, and may be treated by induction of Ag-specific tolerance.

The research team engineered LL to secrete a deamidated DQ8 gliadin epitope (LL-eDQ8d) and then observed the induction of Ag-specific tolerance in NOD AB degrees DQ8 transgenic mice. The team measured tolerance by delayed-type hypersensitivity reaction, cytokine measurements, eDQ8d-specific proliferation, and regulatory T cell analysis.

Oral administration of LL-eDQ8d induced suppression of local and systemic DQ8-restricted T cell responses in NOD AB degrees DQ8 transgenic mice. Result was an Ag-specific decrease of the proliferative capacity of inguinal lymph node (ILN) cells and lamina propria cells. Production of IL-10 and TGF-beta and a significant induction of Foxp3(+) regulatory T cells were associated with the eDQ8d-specific suppression induced by LL-eDQ8d.

These results support the development of orally administered Ag-secreting LL to treat gluten-sensitive disorders. Such treatments may be effective even in cases of established hypersensitivity.

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The research team was made up of G. Trynka, A. Zhernakova, J. Romanos, L. Franke, K. A. Hunt, G. Turner, M. Bruinenberg, G. A. Heap, M. Platteel,1 A. W. Ryan, C. de Kovel, G. K. T. Holmes, P. D. Howdle, J. R. F. Walters, D. S. Sanders, C. J. J. Mulder, M. L. Mearin, W. H. M. Verbeek, V. Trimble, F. M. Stevens, D. Kelleher, D. Barisani, M. T. Bardella, R. McManus, D. A. van Heel, C. Wijmenga.

An earlier celiac disease genome-wide association study (GWAS) identified risk variants in the human leucocyte antigen (HLA) region and eight new risk areas.

To find more celiac disease locations, the research team chose to examine 458 single nucleotide polymorphisms (SNPs) that exhibited weaker ties in the GWAS for genotyping and analysis in four independent cohorts. The 458 SNPs were found among 1682 cases and 3258 controls from UK, Irish and Dutch populations.

The team combined the results with the original GWAS cohort involving 767 UK cases and 1422 controls), in which six SNPs showed association with p,1610. Those six were then genotyped in an independent Italian celiac cohort (538 cases and 593 controls). The research team found two new celiac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL).

In the final combined analysis of all 2987 cases and 5273 controls, both regions achieved genome-wide significance (rs2327832 p=1.3610, and rs842647 p=5.2610).

The researchers used RNA isolated from biopsies and from whole
blood RNA to look at gene expression. They observed no changes in either gene expression, or in the correlation of genotype with gene expression.

From these results, the research team concluded that both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kB) inflammatory signalling pathway.

For the first time, researchers have identified a role for main inherited variation in this important biological pathway that predisposes individuals to celiac disease.

Currently, the HLA risk factors and the 10 established non-HLA risk factors provide an explanation for about 40% of inheritance factors for celiac disease.

Clearly, more research is needed to isolate the other 60% of inheritability factors for celiac disease. Success in this very important area promises to open up the understanding of celiac disease, and to help speed new treatments, and possibly a cure.

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According to the current medical wisdom, innate immunity to gluten plays a critical role in the development of celiac disease (celiac disease).

This innate immune response is caused by a reaction to the ‘toxic’ gluten peptides that is mediated by interleukin (IL) 15, like the 19-mer through a DQ2-independent mechanism, and which causes epithelial stress and triggers the intraepithelial lymphocytes to turn into natural killer (NK)-like cells, which then causes enterocyte apoptosis and a compromised permeability of the cells lining of the gut…and, violà, celiac disease!

It is by breaching this lining that immuno-dominant peptides, such as the 33-mer peptide, come into contact with the lamina propria, which triggers adaptive immunity.

The innate specific response in celiac disease has been pretty well documented, but until recently, no one had described any differential factors between people with celiac disease and those without.

Since the toxic 19-mer triggers its damaging effects through a DQ2-independent mechanism, doctors wondered whether the innate immune response was common in both people with and without celiac disease, and whether the adaptive response is emblematic only of susceptible people with celiac disease.

A team of researchers recently set out to determine just that, beginning with biopsies from at least three patients with celiac disease who were observing a gluten-free diet and three patients who are free of celiac disease. The research team consisted of D. Bernardo, L. Fernandez-Salazar, J. A. Garrote and their colleague S. Riestra, all based in Spain.

The team applied crude gliadin, the gliadin synthetic 19-mer and deaminated 33-mer peptides to the biopsy tissue after discarding the presence of lipopolysaccharide.

They did this at concentrations of 100 mg/ml for 3 hours to mimic what are considered the standard timing and concentration in the digestive tract after a routine meal.

The research team then washed the specimens and cultured them for 21 hours in new clean culture medium to assess whether an innate stimulus is reflected by an adaptive response.

Here’s some technical jargon:

Each sample cultured in basal medium served as an internal control. Innate immune mediators IL15 and nitrites were measured by western blot in the biopsy protein extract along with a Griess reagent system in the 3 h supernatants respectively. mRNA levels of adaptive immunity mediators like signal transducers and activators of transcription (STAT) 1, STAT3, tumour necrosis factor a, interferon (IFN) c, IL23 (p19), IL27 (p28) and IL12 (p35) were determined by real-time polymerase chain reaction using b actine levels as house-keeping.

Compared with the basal culture, all of the patients were challenged with the gliadin solution, and all of the patients, both those with and those without celiac disease on a gluten free diet, showed IL15 production, which indicates an immune reaction is taking place.

More importantly, the IL15-mediated response in patients without celiac disease was triggered, in three of six cases, by the same toxic 19-mer gliadin peptide and, in five of six cases, by the 33-mer gliadin peptide as in those with celiac disease.

Significantly, none of the basal cultures showed this result, though the ‘‘non-toxic’’ immuno-dominant 33-mer did induce an innate response that was un-foreseen.

Interestingly, one patient with celiac disease and on a gluten-free diet, and three patients without celiac disease, who were also on gluten-free diets, all showed the IL15 response, which was confirmed by western blot analysis. This discounts an intracellular and non-biologically active IL15 response in patients without celiac disease.

The gliadin-challenged patients with celiac disease who were on a GFD, showed increased nitrite levels, which those without celiac disease did not show. Following the biopsy mRNA isolation, only patients with celiac disease showed modifications to what are called adaptive mediators (STAT1, STAT3, IFNc).

The basal samples of those celiac patients on a gluten-free diet showed
IFNc mRNA levels that were 80 times higher than basal samples of those without celiac disease (p value 0.002), along with a slightly higher production of nitrites (p value 0.052).

This appears to be the first time that researchers have described an IL15-mediated innate response to gliadin and gliadin peptides in people without celiac disease, as well as the first time they have described an IL15-mediated innate response to the ‘non-toxic’ deaminated immuno-dominant 33-mer peptide.

What this all means is that, for the first time, scientists have documented harmful effects of gluten on people without celiac disease. This hypothesis seems to be born out by the fact that all individuals who took place in the study, both those with and those without celiac disease, showed an innate immune response to gluten, though only those with celiac disease showed an adaptive immune response to gluten.

Clearly, before doctors can draw any hard and fast conclusions, they will need to do more studies on larger groups.

The research team also suggests that people with celiac disease have a lower threshold for triggering an adaptive TH1 response than do non-celiacs, and that people with celiac disease need to be DQ2 positive.

The reason for the differences in threshold levels between celiacs and non-celiacs might be tied to the fact that celiac patients show higher basal levels of immune mediators, such as IFNc mRNA, compared to those without celiac disease. That’s one possibility.

The difference in threshold levels might also have to do with some kind of defect in permeability of the gut membrane in those with celiac disease, or even a greater IL15-sensitivity response under equal stimulus, which might be mediated by a higher density of IL15 receptor in patients with celiac disease.

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Finland has set out to achieve high detection rate by training health personnel, and advocating blood tests for people known to be at risk for developing celiac disease.

A team of researchers recently set out to determine whether this approach has been clinically effective in practice. The research team was made up of Lauri J. Virta, Katri Kaukinen & Pekka Collin.

Since 2002, Finland's Social Insurance Institution had paid monthly compensation to people with newly diagnosed celiac disease for the additional cost of maintaining a gluten-free diet. To receive this compensation, people must submit proof of diagnosis, including biopsy findings, along with diagnostic criteria, in a statement from a physician. That information is kept in a national database. The researchers used the database to calculate incidence and prevalence rates of celiac disease through 2006.

From the database, they selected from a total population aged 16 years or older of 4.31 million, to identify a total of 5020 persons (64% female) who received a new dietary grant in 2004-06. Altogether, 23,553 persons received the dietary grant. Thus, the mean annual incidence of proven celiac disease to be 39 per 100,000 individuals.

This puts the national prevalence of adult celiac disease in Finland at 0.55% (0.70% F, 0.38% M). The results varied by region from 33 to 49 per 100,000 in annual incidence, and from 0.41% to 0.72% in the prevalence rates.

It seems these figures for proven celiac disease in Finland are the highest yet charted. Nevertheless, many celiac disease cases remain undetected, as the true prevalence in Finnish adults is about 1.5-2.0%. Increased alertness to the condition and active case finding has made this efficient diagnostics possible.

Interestingly, people aged 65 to 74 years showed the highest prevalence; in females prevalence peaked at 1.10% (95% Cl: 0.98-1.23) at the age of 68 years and in males, 0.77% (95% CI: 0.67-0.89), also at 68 years. Also, earlier findings have shown that 10-15% of cases will be detected because of atypical symptoms or associated conditions.

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However, researchers recently showed a high number of both diagnosed and undetected celiac disease cases among elderly people. Currently, scientists know very little about the appearance of celiac disease in elderly people.

A team of researchers based in Finland recently set out to examine the increasing prevalence and high incidence of celiac disease among the elderly. The research team was made up of Anitta Vilppula, Katri Kaukinen, Liisa Luostarinen, Ilkka Krekelä, Heikki Patrikainen, Raisa Valve, Markku Mäki and Pekka Collin.

The team evaluated the prevalence of celiac disease in people over 55 years of age, and assessed the incidence of biopsy-proven celiac disease (CDb) and celiac disease including seropositive subjects for anti-tissue transglutaminase antibodies (CDb+s).

The team based their study on celiac disease prevalence figures in 2815 randomly selected subjects who had undergone a clinical examination and serologic screening for celiac disease in 2002.

A second screening in the same population was carried out in 2005, comprising now 2216 individuals. The team confirmed positive tissue transglutaminase antibodies results with small bowel biopsy.

Over a three year period, the prevalence of CDb increased from 2.13 to 2.34%, and that of CDb+s from 2.45 to 2.70%. 

Five new cases emerged from five previously seronegative patients; two showed minor abdominal symptoms and three were asymptomatic. Celiac disease incidence in 2002–2005 was 0.23%, for an annual incidence of 0.08%.

It's unclear whether the number of undetected cases in the elderly is due to diagnostic delay, or to the development of celiac disease at a more advanced age, or both.

In closing, elderly people showed higher rates of celiac disease, but with subtle symptoms. Repeated screening detected five biopsy-proven cases in three years, indicating that the disorder may arise late, even among the elderly. The researchers are therefor recommending that doctors treating elderly patients employ an increased alertness as to the possible presence of celiac disease.

BMC Gastroenterology 2009, 9:49

Gut Reaction: Environmental Effects on the Human Microbiota
Melissa Lee Phillips
Published on Medscape.com: 07/15/2009
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It may be years before research fully understands how gut microbiota and vitamin D deficiency may be involved in triggering celiac disease. Both vitamin D and probiotic supplements (such as Bifidobacterium infantis) are cheap, readily available, and generally safe. There is much current research showing how important vitamin D is for overall health. Your infant's health is a matter of immediate concern and cannot wait 5 or 10 years for research to confirm whether such supplements can help prevent celiac disease. It would seem prudent to make use of these supplements now in both mother and infant during pregnancy, while breast-feeding, and prior to introducing gluten to your baby. Consult with your physician about how much is the right dose.

Celiac disease is the most common genetic autoimmune disease in the world. Celiac disease affects approximately three million Americans, but only three out of every one hundred people with celiac disease have been diagnosed.

At least ninety-seven percent of people with celiac disease undiagnosed. Untreated celiac disease can lead to osteoporosis, infertility, neurological conditions, and cancer. Moreover, people with celiac disease have a substantially higher risk of developing other autoimmune diseases, especially Type-1 diabetes.

Bana Jabri, M.D., Ph.D., Associate Professor, University of Chicago Medical Center, and a leading celiac disease researcher, will create the new mouse model with the goal of identifying new remedies and preventive treatments targeted at children of families with a history of celiac disease. The studies will also investigate events that contribute to the development of Type-1 diabetes.

“There is a critical need to provide the proper resources to those who suffer from celiac disease,” said Stefano Guandalini, M.D., professor of pediatrics at the University of Chicago Medical Center, founder and medical director of the Celiac Disease Center. “This commitment from University of Chicago Celiac Advisory Board reaffirms the Celiac Disease Center’s mission to bring cutting edge research, education and encouragement to those affected by the disease”.

Dr. Jabri believes that mouse models are central to understanding the underlying causes of celiac disease, its connection to other autoimmune diseases.

The University of Chicago Celiac Disease Center is a 501-c3 non-profit organization, completely funded by donor contributions, and committed to improving the care, diagnosis and awareness of celiac disease. The University of Chicago Celiac Disease Center also provides necessary infrastructure and support for cutting-edge celiac research, including investigations into structure of gluten peptides and the mechanisms by which gluten modifies self molecules.

Mouse model studies show promise in helping researchers to better and more quickly unlock the secrets of celiac disease.

For more information please visit: www.celiacdisease.net 

Celiac disease is an immune system reaction to gluten in the diet which, left untreated, celiac disease causes damage to the lining of the digestive tract and leaves sufferers at risk for various cancers and other associated conditions. When people with celiac disease eat wheat, barley or rye, a protein called gluten triggers an immune system attack, which damages the villi in the small intestine.Villi are finger-like folds in the intestine that increase surface area for nutrient absorption.

Celiac disease symptoms may include diarrhea, abdominal discomfort, weight loss, anemia, unexplained infertility, loss of teeth or even premature or severe osteoporosis, among others.

Joseph Murray, M.D., the Mayo Clinic gastroenterologist who led the study says celiac disease "now affects about one in a hundred people. We also have shown that undiagnosed or 'silent' celiac disease may have a significant impact on survival. The increasing prevalence, combined with the mortality impact, suggests celiac disease could be a significant public health issue."

So, celiac disease is striking a higher than ever portion of the population, yet doctors don't yet fully understand the reasons for this reality.

A team of Mayo Clinic scientists team performed celiac disease antibody tests on blood samples gathered at Wyoming's Warren Air Force Base (AFB) between 1948 and 1954. They then compared those blood test results with results from two recently collected groups from Olmsted County, Minn. Tests for the first group were matched by age to those from the Warren AFB group at the time of the blood draw, while the second group was matched by birth years.

Researchers found that young people today are 4.5 times more likely to have celiac disease than young people were in the 1950s, while those whose birth years matched the Warren AFB participants were four times more likely to have celiac disease.

Celiac disease was once thought to be rare, and many physicians still regard it as so, but, according to Dr. Murray, that is no longer the case.
"Celiac disease is unusual, but it's no longer rare," he says.

Dr. Murray adds: "Something has changed in our environment to make it much more common. Until recently, the standard approach to finding celiac disease has been to wait for people to complain of symptoms and to come to the doctor for investigation. This study suggests that we may need to consider looking for celiac disease in the general population, more like we do in testing for cholesterol or blood pressure."

For Dr. Murray, the findings underscore the importance of raising awareness of celiac disease, both among physicians and patients. He adds that some studies "have suggested that for every person who has been diagnosed with celiac disease, there are likely 30 who have it, but are not diagnosed. And given the nearly quadrupled mortality risk for silent celiac disease we have shown in our study, getting more patients and health professionals to consider the possibility of celiac disease is important."

One interesting point not touched on in the study is the increase in the gluten content of commercial varieties of wheat now being grown compared to gluten levels of 50 years ago. Additionally, people are eating more wheat and gluten than ever before.

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Gastroenterology, July 2009;137(1)pp 373-374

Only a small number of genetically predisposed individuals show a toxic  small bowel mucosa reaction to gliadin. Since levels of immunogenic gliadin may vary between different wheat species, a team of researchers first set out to assess immunogenic gliadin levels in ten bread wheat types and in three strains of commercially grown durum wheat.

The team was made up of Aleksandra Konic-Ristic, Dejan Dodig, Radmilo Krstic, Svetislav Jelic, Ivan Stankovic, Aleksandra Ninkovic, Jelena Radic, Irina Besu, Branka Bonaci-Nikolic, Njegica Jojic, Milica Djordjevic, Dragan Popovic, and Zorica Juranic.

They were spurred by previous studies that showed sera of some of multiple myeloma (MM) patients with elevated levels of anti-gliadin IgA, without enhanced levels of anti-gliadin IgG antibodies, as determined by commercial ELISA test.

They designed their own specifically to uncover any hidden anti-gliadin IgG immunoreactivity in patient blood samples. For this reason, researchers tested blood of both MM patients and celiac disease patient for immunoreaction with native gliadin isolated from regional wheat species used for bread and pasta making.

The team isolated gliadin from wheat flour by two step 60% ehanolic extraction. They determined gliadin levels by commercial R5 Mendez Elisa using PWG gliadin as the standard.

Results showed immunogenic gliadin content varies between 50.4 and 65.4 mg/g in bread wheat samples and between 20 and 25.6 mg/g in durum wheat samples.

Anti-gliadin IgA and IgG immunoreactivity of patients'sera in (IU/ml) was first measured by commercial diagnostic Binding Site ELISA test, and then additionally by non-commercial ELISA tests, using standardized ethanol wheat extracts -gliadin as the antigen.

In both patient groups, IgA immunoreactivity to gliadin from different samples was almost homogenous and in correlation with results from commercial test, except for one IgA(lambda) myeloma patient. However, results for IgG immunoreactivity were less homogeneous.

Results showed different immunogenic gliadin epitope levels in various species of wheat. They also point to a need for developing a new standard antigen, a representative mixture of gliadin isolated from local wheat species used for bread production in corresponding geographic region for ELISA diagnostic tests.

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