Jump to content
  • Sign Up
  • Welcome to Celiac.com

  • Member Statistics

    84,357
    Total Members
    4,125
    Most Online
    L. Hackstaff
    Newest Member
    L. Hackstaff
    Joined
  • 0

    New Therapy May Mean Less Dietary Restrictions for Celiac Disease Sufferers


    Scott Adams

    Celiac.com 07/01/2006 - Scientists have discovered what may be a successful non-dietary therapy for celiac sprue, an inherited inflammatory disorder of the small intestine that impacts an estimated 1 in 200 people around the world. Two research studies, published in the June issue of Chemistry and Biology, pave the way for clinical testing with an oral enzyme therapy that may prevent the many symptoms and complications of this widespread disease.

    People with celiac sprue, also called celiac disease, cannot tolerate the protein gluten in their diet. Gluten is present in grains like wheat, barley, and rye. When gluten is ingested by a celiac patient, it sets off an inflammatory reaction that damages the small intestine, leading to malabsorption, an autoimmune-like response, and many other complications. The only effective therapy for celiac disease is complete dietary exclusion of gluten. However, the ubiquitous nature of gluten poses a constant threat to celiacs, and a majority of celiac patients who adopt a restrictive diet still exhibit structural and functional gut abnormalities.

    "Non-dietary therapies that allow celiac patients to safely incorporate low-to-moderate levels of gluten into their daily diet would be of considerable benefit," explains study leader Dr. Chaitan Khosla, from Stanford University and Celiac Sprue Research Foundation. "Having demonstrated earlier that certain types of enzymes can detoxify gluten, our laboratory set out to devise an optimal oral enzyme therapy for celiac sprue by borrowing from nature. In germinating barley seed, gluten serves as a nutritious storage protein that is efficiently digested by enzymes. One enzyme, EP-B2, plays a crucial role in this process by breaking gluten proteins after glutamine residues, which comprise one-third of all amino acid residues in gluten."

    Dr. Khoslas group used recombinant bacteria to produce a form of EP-B2 that only activates under acidic conditions similar to the conditions found in the human stomach. The researchers demonstrated that EP-B2 efficiently digested gluten protein under gastric conditions and, importantly, EP-B2 was most specific for those parts of gluten that are known to trigger celiac pathogenesis. In a second study, the researchers went on to devise an even more potent double enzyme therapy for detoxifying gluten.

    EP-B2 was tested in combination with another well-characterized enzyme called PEP that breaks gluten protein after proline residues. Like glutamine, proline is also abundant in inflammatory gluten peptides. At very high gluten loads, where neither PEP nor EP-B2 alone could detoxify gluten quickly enough to prevent inflammation, a PEP and EP-B2 combination completely abolished gluten immunotoxicity within ten minutes under simulated gastric and duodenal conditions.

    In this tag-team therapy, EP-B2 first cleaved gluten into small pieces under gastric conditions that were then easier for PEP to fully detoxify under duodenal conditions. "Our results suggest that recombinant EP-B2 should be effective as supportive therapy to help celiacs cope with the hidden gluten in everyday life, and that a two-enzyme cocktail containing PEP and EP-B2 may even allow celiacs to resume a more normal diet in the future," offers Dr. Khosla.

    References:

    Seigel et al.

    The researchers include Matthew Siegel, Michael T. Bethune, Jiang Xia, Alexandre Johannsen, Tor B. Stuge, and Peter P. Lee of Stanford University in Stanford, CA; Jonathan Gass, Jennifer Ehren, Gary M. Gray, and Chaitan Khosla of Stanford University in Stanford, CA and Celiac Sprue Research Foundation in Palo Alto, CA. This research was supported by a grant from the National Institutes of Health (R01 DK63158 to C.K. and Mary Hewitt Loveless, MD Pilot-Project Grant to P.P.L.).

    Siegel et al.: "Rational Design of Combination Enzyme Therapy for Celiac Sprue." Publishing in Chemistry & Biology 13, 649–658, June 2006 DOI 10.1016/j.chembiol.2006.04.009 www.chembiol.com

    Bethune et al.

    The researchers include Michael T. Bethune, Yinyan Tang, and Chaitan Khosla of Stanford University in Stanford, CA; Pavel Strop of Howard Hughes Medical Institute and Stanford University in Stanford, CA; Ludvig M. Sollid of University of Oslo and Rikshospitalet University Hospital in Oslo, Norway. This research was supported by R01 DK063158 to C.K. M.T.B. is a recipient of a National Institutes of Health Cellular and Molecular Biology Training Grant through Stanford University.

    Bethune et al.: "Heterologous Expression, Purification, Refolding, and Structural-Functional Characterization of EP-B2, a Self-Activating Barley Cysteine Endoprotease." Publishing in Chemistry & Biology 13, 637–647, June 2006 DOI 10.1016/j.chembiol.2006.04.008 www.chembiol.com.

    Contact: Heidi Hardman
    Tel: (617) 397-2879

    0


    User Feedback

    Recommended Comments

    Guest Christine

    Posted

    Please, Bring it on, we will try anything just to eat again.... The article of research was in 2006 it is 2009 What happen?

    Share this comment


    Link to comment
    Share on other sites


    Your content will need to be approved by a moderator

    Guest
    You are commenting as a guest. If you have an account, please sign in.
    Add a comment...

    ×   Pasted as rich text.   Paste as plain text instead

      Only 75 emoji are allowed.

    ×   Your link has been automatically embedded.   Display as a link instead

    ×   Your previous content has been restored.   Clear editor

    ×   You cannot paste images directly. Upload or insert images from URL.


  • About Me

    In 1994 I was diagnosed with celiac disease, which led me to create Celiac.com in 1995. I created this site for a single purpose: To help as many people as possible with celiac disease get diagnosed so they can begin to live happy, healthy gluten-free lives. Celiac.com was the first site on the Internet dedicated solely to celiac disease. In 1998 I founded The Gluten-Free Mall, Your Special Diet Superstore!, and I am the co-author of the book Cereal Killers, and founder and publisher of Journal of Gluten Sensitivity.

  • Popular Contributors

  • Related Articles

    Scott Adams
    J Pediatr. 2004 May;144(5):632-6
    Celiac.com 05/10/2004 - Italian researchers compared the serum samples from 39 celiac disease patients who were diagnosed with celiac disease after their first biopsy with 32 controls who had normal duodenal mucosa and 32 healthy volunteers. Salivary transglutaminase autoantibodies were detected in 97.4% of the patients who had celiac disease, and in 100% of their corresponding serum samples. All of the 32 healthy volunteers tested negative for both serum and saliva transglutaminase autoantibodies. The researchers conclude "This study demonstrates that it is possible to detect salivary transglutaminase autoantibodies in celiac disease with a non-invasive, simple to perform, reproducible and sensitive method."

    Dr. Ron Hoggan, Ed.D.
    This article appeared in the Autumn 2005 edition of Celiac.coms Scott-Free Newsletter.
    Celiac.com 01/11/2006 - There is an abundance of stories about people who begin a gluten-free diet, find that they feel better then decide they want a firm diagnosis of celiac disease. They are facing several problems. First, they may be gluten sensitive without the intestinal lesion of celiac disease. This is very likely since about twelve percent of the population is gluten sensitive, but only a little more than one percent of the general population has celiac disease. Another problem faced by gluten-free individuals who want a diagnosis is that it can take more than five years after returning to a regular gluten-containing diet before the characteristic damage of celiac disease can be seen on a biopsy1. Simply put, after beginning a gluten-free diet, only a positive biopsy is meaningful. A negative biopsy does not rule out celiac disease.
    A variety of opinions have been offered regarding how much gluten, for how long, should result in a definitive biopsy. The reality is that no such recommendation is consistent with the medical literature1-4. Some people with celiac disease will experience a return of intestinal damage within a few weeks of consuming relatively small amounts of gluten. Such brief challenges are valuable for these individuals. However, many people with celiac disease or dermatitis herpetiformis will require much larger doses of gluten, over much longer periods, to induce characteristic lesions on the intestinal wall. Unfortunately for these latter individuals, a negative biopsy after a brief gluten challenge can, and often is, misinterpreted as having ruled out celiac disease. Blood tests can compound this problem. If, as seems likely, celiac patients who are slow to relapse are also the ones who develop milder intestinal lesions, they are the very celiac patients for whom blood tests are very unreliable5. Claims to have ruled out celiac disease based on brief challenges with small quantities of gluten is a mistake that could lead to serious, even deadly, consequences.
    We may forget that gluten consumption by a person with celiac disease can lead to deadly cancers and a variety of debilitating autoimmune diseases. Any recommendation of a gluten challenge should be accompanied by a clear warning that the process may overlook many cases of celiac disease. The absence of such warnings is inexcusable.
    And what about non-celiac gluten sensitivity? The absence of an intestinal lesion does not rule out gluten induced damage to other tissues, organs, and systems. Evidence and research-based information in this area is sadly lacking but we do know that undigested or partly digested gliadin can damage a wide range of human cells6. Thus, one need only be consuming gluten and experience increased intestinal permeability for gluten-induced damage to be a factor in an almost infinite number of ailments.
    There are several partial answers to this problem. One, which Ive raised before, is to employ Dr. Michael N. Marshs rectal challenge for the diagnosis of celiac disease, particularly when the individual has already begun a gluten-free diet. This test permits a definitive diagnosis of celiac disease for up to six months after beginning a gluten-free diet. That would catch a great number of celiac patients who have found relief through a gluten-free diet and now want a diagnosis. Another piece of this puzzle is to test for IgG anti-gliadin antibodies. Although these antibodies are considered "non-specific," they inarguably identify an immune response to one of the most common foods in a regular North American diet. Although these individuals may experience improved wellness on a gluten-free diet, we just dont know enough about non-celiac gluten sensitivity to do more than recommend that they continue on this diet since it makes them feel better.
    Ron Hoggan is an author, teacher and diagnosed celiac who lives in Canada. His book "Dangerous Grains" can be ordered at Celiac.com. Rons Web page is: www.DangerousGrains.com.
    References:
    Kuitunen P, Savilahti E, Verkasalo M. Late mucosalrelapse in a boy with coeliac disease and cows milk allergy.Acta Paediatr Scand.1986 Mar;75(2):340-2. Bardella MT, Fredella C, Trovato C, Ermacora E, Cavalli R, Saladino V, Prampolini L. Long-term remission in patients with dermatitis herpetiformis on a normal diet. Br. J. Dermatol. 2003 Nov;149(5):968-71. Shmerling DH, Franckx J. Childhood celiac disease: a long-term analysis of relapses in 91 patients.J Pediatr Gastroenterol Nutr. 1986 Jul-Aug;5(4):565-9. Chartrand LJ, Seidman EG. Celiac disease is a lifelong disorder. Clin Invest Med. 1996 Oct;19(5):357-61. Rostami K, Kerckhaert J, von Blomberg BM, Meijer JW, Wahab P, Mulder CJ. SAT and serology in adult coeliacs, seronegative coeliac disease seems a reality.Neth J Med. 1998 Jul;53(1):15-9. Hudson DA, Cornell HJ, Purdham DR, Rolles CJ. Non-specific cytotoxicity of wheat gliadin components towards cultured human cells.Lancet. 1976 Feb 14;1(7955):339-41.

    Gryphon Myers
    Intestinal Biopsy is Not Necessarily Required to Diagnose Celiac Disease
    Celiac.com 02/18/2013 - Currently, there are two main diagnostic tools available to would-be celiacs: biopsy and serological (antibody) tests. For the past few decades, biopsy has been the only relatively reliable (and diagnostically accepted) path to diagnosis. The problem is, biopsies are expensive and highly invasive – antibody tests would be a cheap and painless alternative, but they haven't proven themselves to be accurate enough for conclusive diagnosis. However, a recent analysis shows that antibody tests have improved a great deal in recent years and when used to test for multiple antibodies concurrently, they can be almost as effective as biopsies for diagnosing celiac disease.
    The study's facilitators began their restrospective analysis by collecting serum samples from 268 patients at hospitals throughout Switzerland, Germany and Austria. All included patients suffered from celiac-like symptoms and underwent both biopsy and antibody testing within 2 months of serum collection. All included patients were on gluten-containing diets at the time of testing. 149 of the patients were ultimately diagnosed with celiac disease; the other 119 showed normal intestinal mucosa and were considered celiac-free. These patients were the control group.
    Usually, potential celiac patients are tested for IgA anti- tTG or EMA. If the test is positive, then diagnosis is then confirmed with biopsy. However, there is still a chance that the test will throw a false positive, meaning many people are put through unnecessary biopsies. The goal of the present study was to develop a method for reducing the number of these unnecessary biopsies.
    It was found that when two antibody tests are used, the reliability of the tests increased substantially, weeding out a great many false positives, as well as picking up some false negatives. When three tests were used, the numbers became even more accurate – when used concurrently and all three show a positive result, the IgA anti-dpgli, igG anti-dpgli and IgA anti-tTG achieved an 87% positive likelihood and .01% negative likelihood (compared to a positive likelihood of only 7% and negative likelihood of 0.04% with just the IgA anti-tTG). Using these three tests together, only one test subject came through as a false positive, and only two came through as false negatives (compared to 16 false positives and 5 false negatives with the IgA anti-tTG only). 60 came through with discordant results (meaning at least one of the tests came back negative – in these cases, biopsy is necessary).
    When considering that biopsy really only has a real-world diagnostic accuracy rate of about 90%, the three test combination utilized in this study achieves strong enough numbers that biopsies are starting to look unnecessary. Biopsy still might be the surest way of detecting celiac disease, but this study shows that it is not necessary in all cases, and patients seeking celiac diagnosis have a few more tests they can ask their doctors for.
    Source:
    http://www.biomedcentral.com/1471-230X/13/19

    Jefferson Adams
    What if I Have Villous Atrophy but Negative Celiac Blood Tests?
    Celiac.com 06/27/2013 - Patients with villous atrophy and negative celiac disease serologies pose a diagnostic and therapeutic dilemma.
    When doctors are unable to determine what is causing villous atrophy in a patient without celiac disease, they usually classify it as a case of "unclassified sprue." However, doctors currently know very little about the best way to treat and manage cases of unclassified sprue.
    To get a better picture of this dilemma, a team of researchers recently examined the connections between villous atrophy and negative celiac serology.
    The research team included M. Degaetani, C.A. Tennyson, B. Lebwohl, S.K. Lewis, H. Abu Daya, C. Arguelles-Grande, G. Bhagat G, and P.H. Green. They are variously affiliated with the Celiac Disease Center, and the Department of Medicine at Columbia University College of Physicians and Surgeons at Columbia University Medical Center in New York, USA.
    For their study, the team looked at adult patients with biopsy-proven villous atrophy and negative celiac serology, evaluated at our tertiary referral center over a 10-year period.
    They noted test results for HLA DQ2/8 alleles, antienterocyte antibodies, giardia stool antigen, bacterial overgrowth, total serum immunoglobulins, and HIV. They also recorded treatment, response, and repeat-biopsy findings for each patient.
    They found that most of the 72 cases were classified as seronegative celiac disease, medication-related villous atrophy, and unclassified sprue.
    The majority of patients diagnosed with unclassified sprue reported symptomatic improvement with immunosuppressive therapy.
    Some patients diagnosed with unclassified sprue were found to have villous atrophy associated with the use of olmesartan.
    The team encourages further examination of the role of medications in the development of villous atrophy, along with the optimal dose and length of immunosuppression for patients with unclassified sprue.

    Source:
    Am J Gastroenterol. 2013 May;108(5):647-53. doi: 10.1038/ajg.2013.45.

×