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    Wheat Protein Show Growth-factor like Activity in the Gut


    Jefferson Adams

    Celiac.com 04/23/2007 - A study published in a recent issue of the journal Gut suggests that wheat gliadin might trigger pathological development in mucosal cells that are already abnormal, but otherwise tolerated, within the intestinal tracts of individuals with celiac disease.

    Researchers at the Universita degli Studi di Napoli Federico II in Naples, Italy, led by Dr. Salvatore Auricchio looked at the effects of gliadin peptides on various cell lines and celiac mucosal cells in culture.

    More specifically, the study evaluated the effects of gliadin and affiliated toxic peptides such as A-gliadin P31-43 on endocytosis, cell proliferation, apoptosis, cytoskeleton rearrangements, and activation of epidermal growth factor receptor (EGFR).

    The researchers report that gliadin peptides induce EGF-like effects across a wide range of cell types. Actin rearrangements and cell proliferation are examples of these effects. Also, they state that gliadin peptides act not as ligands of the EGF receptor, but that they actually inhibit EGFR endocytosis.

    According to the research team, these observations of gliadin-induced delay of EGFR endocytosis, along with S-phase entry of epithelial intestinal cells, clearly indicate that EGFR plays a role in celiac disease. Dr. Auricchio proffers that a genetic factor in celiacs may bring about deregulated activity in the endocytotic pathway that is compensated in the absence of gliadin.

    The study concludes that wheat gliadin slows receptor deactivation of Epidermal Growth Factor. This may explain how wheat gliadin and related cereal prolamines trigger rapid increase in cell growth and associated disease activity in people with celiac disease.

    Gut 2007;56:480-488.

     

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  • About Me

    Jefferson Adams earned his B.A. and M.F.A. at Arizona State University, and has authored more than 2,000 articles on celiac disease. His coursework includes studies in biology, anatomy, medicine, and science. He previously served as Health News Examiner for Examiner.com, and provided health and medical content for Sharecare.com.

    Jefferson has spoken about celiac disease to the media, including an appearance on the KQED radio show Forum, and is the editor of the book Dangerous Grains by James Braly, MD and Ron Hoggan, MA.

  • Related Articles

    Jefferson Adams
    Celiac.com 04/13/2009 - A team of Spanish researchers recently set out to determine rates and clinical status of gluten sensitive enteropathy (GSE) detected by mass blood screens. The researchers also sought to determine sensitivity of anti-transglutaminase (tTGA) and anti-endomysium antibodies (EmA) in diagnosis, and compliance with a gluten-free diet (GFD) and follow-up.
    The research team was made up of doctors Meritxell Mariné, Fernando Fernández-Bañares, Montserrat Alsina, Carme Farré, Montserrat Cortijo, Rebeca Santaolalla, Antonio Salas, Margarita Tomàs, Elias Abugattas, Carme Loras, Ingrid Ordás, Josep M Viver, and Maria Esteve.
    Researchers recruited one thousand, eight hundred and sixty eight subjects, who were the screened for tTGA and EmA.
    Positive screens were referred for duodenal biopsy, DQ2/DQ8 genotyping, clinical feature charting, blood tests, and densitometry.
    More than 98% of subjects showed tTGA levels below 2 U/mL,
    so researchers designated this as the baseline level for normality, and deemed results positive at or above this level if confirmed twice in a single sample. Researchers also charted adherence to a GFD and follow-up results.
    A total of 26 subjects (1.39%) showed positive tTGA and/or EmA results, Of those, 21 underwent biopsy, with results showing six Marsh â…¢ (one â…¢a, four â…¢b, one â…¢c), nine Marsh â…  and six Marsh 0, with a GSE rate of 1:125.
    EmA sensitivity for GSE was 46.6% (11.1% for Marsh â… , 100%
    for Marsh â…¢), while tTGA, sensitivity was 93.3% (88.8% for Marsh â… , 100% for Marsh â…¢).
    All 15 patients with abnormal blood tests showed clinical manifestations related to GSE. Marsh â…  and â…¢ subjects showed more abdominal pain than Marsh 0 (P = 0.029), and also showed more distention and diarrhea. The team saw no differences in the rates of osteopenia between Marsh â…  and â…¢ (P = 0.608). They found that 66.7% of the 15 GSE patients complied with a gluten-free diet, and that 80% responded positively to the diet. 69.2% participated in follow-up study.
    This study showed positive blood screens in nearly 1.4% of those tested. The study showed frequent and clinically relevant rates of GSE among the general population. This confirms that celiac disease and related conditions are at least as common as the 1% figure commonly quoted, and indicate that when criteria are expanded to include less severe cases, they may be even higher.
    The study confirmed tTGA as the marker of choice, and showed that mass screening programs such as this one are helpful in spotting celiac disease early, and in referring people for treatment and follow-up before the disease develops into more costly and debilitating conditions often associated with untreated celiac disease.


    World J Gastroenterol. 2009 March 21; 15(11): 1331–1338.

    Destiny Stone
    The Importance of  Medical Follow-up After a Positive Celiac Disease Diagnosis
    Celiac.com 07/26/2010 - There is very little information currently available regarding the effects of follow up strategies for those celiac patients that follow a gluten-free diet. Therefore, it was the aim of of researchers in Italy to determine the t-transglutaminase antibodies (t-TG) in celiac disease patients while they were enrolled in a community based follow-up program over a 5-year period.
    Most patients that are diagnosed with celiac disease are told they need to adhere to a gluten-free diet for the remainder of their lives, and then they are usually left to figure it out on their own. However, it is recommended that celiac patients have regularly scheduled  follow-ups after diagnosis for early detection of celiac related complications, and to reinforce the importance of adhering strictly to a gluten-free diet.
    In the year 2000, a community based “celiac disease-Watch” follow-up program was designed by the Local Health Authority of the Brescia Province in Northern Italy. The hope for the celiac disease-Watch program was to increase awareness of celiac disease  and to standardize diagnostic criteria  for celiac disease among health care professionals.
    Beginning in January 2003, all celiac patients that reside in the Province of Brescia have been enrolled in an ongoing celiac disease-Watch follow-up program. To encourage celiac patients to enroll in the follow-up program, the Italian government gives patients a bonus to subsidize their gluten-free diets, and all patients are required to contact the Local Health Authority every year to renew their bonuses.
    Furthermore, the celiac disease-Watch program requires all patients to have their serum tested once a year for detection of t-TG antibodies. Testing for the antibodies begins 12-16 months after a celiac diagnosis. The testing is free of charge to the patients and they can choose any laboratory they like. Results from the t-TG testing is reported to the Local Health Authority, and it is a requirement to continue to receive subsidization, although patients continue to receive subsidization regardless of their t-TG results.
    Those that test positive for t-TG antibodies during their annual follow up, are referred back to the clinic where they were initially diagnosed. At the clinic they receive a clinical evaluation, and dietary counseling. While those that have a clean bill of health are scheduled for follow up appointments every 3 years.
    Through this study, researchers found that  as a result of the celiac disease-watch program, celiac patients with negative t-TG antibodies advanced from 83% to 93%. Respectively, using mathematical modelling to t-TG conversion rates observed in the study, the projected population of t-TG negative patients increased in population from 90% to 95% over the 5 year period.
    From this study, researchers were able to determine with confidence that without a follow-up strategy in place, patients with celiac disease will be inconsistent with adhering to a gluten-free diet. It is therefore strongly emphasized that regular serological and clinical follow-ups are a sustainable strategy to promote dedicated compliance to a gluten-free diet.
    Source:

    Digestive and Liver Disease doi:10.1016/j.dld.2010.05.009

    Jefferson Adams
    Blocking Interleukin-15 May Treat Celiac Disease Symptoms
    Celiac.com 03/18/2011 - By blocking an inflammatory protein called interleukin-15 (IL-15), doctors may be able to treat and prevent symptoms of celiac disease in some people, according to a new study in the journal Nature.
    The data suggest that the inflammatory response to gluten in people with celiac disease may be triggered by interleukin-15 and retinoic acid, which is a derivative of vitamin A.
    The team notes that researchers previously thought that retinoic acid would lessen the inflammation in the intestine. Instead their study showed that it might actually worsen inflammation.
    According to Bana Jabri, MD, PhD, a member of the Celiac Disease Center and Comprehensive cancer Center at the University of Chicago, the team results showed that "elevated levels of IL-15 in the gut could initiate all the early stages of celiac disease in those who were genetically susceptible, and that blocking IL-15 could prevent the disease in our mouse model. It also demonstrated that in the treatment of inflammatory intestinal diseases, vitamin A and its retinoic acid metabolites are likely to do more harm than good.”
    The researchers found that by blocking IL-15 in mice that were genetically engineered to have celiac disease, they were able to reverse the symptoms, and the mice were able to eat gluten without suffering the symptoms of celiac disease.
    One reason this is good news, is that a number of medicines designed to block IL-15 are already being developed for other inflammation related diseases, such as rheumatoid arthritis.
    Source:

    Nature. 2011 Mar 10;471(7337):220-4.

    Jefferson Adams
    How Reliable is Hepatitis B Vaccination in People with Celiac Disease?
    Celiac.com 02/10/2012 - The HBV vaccine is usually effective against common hepatitis B virus (HBV) infection, with just 4-10% of vaccine recipients failing to respond to standard immunization. Some studies suggest that people with celiac disease may have high levels of resistance to the HBV vaccine, compared to the general population.
    A team of researchers recently took a look at the issue of HBV vaccine reliability in people with celiac disease.
    The study team included Mohammad Rostami Nejad, Kamran Rostami, and Mohammad Reza Zali. They are variously affiliated with the Research Center for Gastroenterology and Liver Disease at Shahid Beheshti University of Medical Sciences in Tehran, Iran, and with Acute Medicine at Dudley Group of Hospital in Dudley, UK. Together, they reviewed data from previous studies.
    The ability to respond to recombinant HBV vaccine is associated with certain gene sites. At those sites, certain HLA haplotypes, such as B8, DR3, and DQ2 are common genetic markers among non-responders.
    Since HLA genotypes play an important role in unresponsiveness to the HBV vaccine, and since 90-95% of people with celiac disease have HLA-DQ2, celiac disease may be a factor in this failure to respond to the HBV vaccine.
    For one study, Ertekin et al., a research team gave HBV vaccinations, according to a standard immunization schedule, to 52 children with celiac disease, and another twenty matched for age and sex.
    The average age of the celiac disease patients was 10.7 ± 4 years (range, 4-18 years). Anti-HBs titers were positive in 32 (61.5%) patients and negative in 20 (38.5%) patients, while they were positive in 18 (90%) of the children in the control group (P < 0.05). The review team found statistically significant differences between negative anti-HBs titers, clinical presentation of celiac disease, and dietary compliance in patients with celiac disease (P < 0.05).
    In all, 32 of the 52 children with celiac disease responded favorably to HBV vaccination. This was a substantially lower percentage that the 18 of 20 control subjects responded (P < 0.05).
    Ertekin et al. concluded that a significantly higher percentage of children with celiac disease failed to respond to hepatitis B vaccination, as compared with the control group.
    They concluded that response to the HBV vaccine in children with celiac disease should be investigated, and a different immunization schedule should be developed for them. They suggested that celiac children who follow a gluten-free diet may have a better immune response to the HBV vaccine.
    The data fits with previous studies that confirm the findings that children with celiac disease fail to respond to the HBV vaccine at significantly higher rates than do healthy children.
    In fact, the researchers point out a similar study on adults, Noh et al., revealed that, of 23 adults with celiac disease who had completed a full course of HBV vaccination, 19 tested positive for HBsAb and 13 failed to acquire proper long-term immunity.
    Another study, by Stachowski et al., further cemented this connection between HLA and non-responsiveness to HBV vaccine. In that study, 34 out of 153 patients with end-stage renal disease failed to respond to HBV vaccine, and HLA-DQ2 was found almost exclusively in the non-responder group.
    Long stretches of time between vaccination and antibody testing might be one reason even celiac disease patients who follow a gluten-free diet have significantly reduced post-vaccination levels of HBV antibody. Therefore, current guidelines recommend revaccinating celiac patients once they have established a reliable gluten-free diet.
    This study was not designed to assess the presence of HLA-DQ2 and HLA-DQ8 in the groups. Therefore, future studies assessing HLA haplotypes in celiac disease should seek to describe the role of HLA typing in response to HBV vaccination.
    The evidence indicates that early diagnosis of celiac disease, and treatment with a gluten-free diet may increase the overall percentage of patients responding favorably to the HBV vaccine.
    Treatment of celiac disease with a strict, gluten-free diet seems to play a positive role in the development of antibody memory.
    The review team points out that the high prevalence of celiac disease in the general population and a lack of response to HBV vaccine in untreated patients, invites routine assessment in patients with celiac disease receiving the HBV vaccine.
    Lastly, the review team notes that non-responsiveness to HBV vaccine may indicate undiagnosed celiac disease or noncompliance with gluten-free diet.
    SOURCE:
    Hepat Mon. 2011 August 1; 11(8): 597–598.
    doi:  10.5812/kowsar.1735143X.761


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