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  • Jefferson Adams
    Jefferson Adams
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    High Content Analysis Helpful in Spotting Celiac-Related Lesions Before They Occur

    Celiac.com 09/25/2008 - Mucosal inflammation of the small intestine, coupled with damage to intestinal villi, is a classic indication of celiac disease. Recently, doctors have begun to embrace the idea that some patients with positive celiac blood tests may have mucosal lesions that are too small to appear on routine histopathological analysis.

    In the first study of its kind, a team of researchers based in Ireland set out to analyze enterocyte morphology and cytoskeletal structures using a high content analysis technology.

    The research team was made up of doctors Bashir M. Mohamed, Conleth Feighery, Yvonne Williams, Anthony Davies, Dermot Kelleher, Yuri Volkov, Jacinta Kelly and Mohamed Abuzakouk.

    The team examined duodenal biopsies from 14 untreated and 10 treated celiac patients and from 20 non-celiac control subjects. They also investigated tissue sections from six study group subjects before and after the development of gluten-sensitive enteropathy.

    The research team used an anti-α-tubulin antibody to conduct immunohistochemical studies on paraffin-embedded tissue sections. They found important differences in enterocyte morphology and intracellular cytoskeletal structures in the patients with proven celiac disease and those in the study group.

    Moreover, the team observed that these changes existed in the study group prior to any indication of enteropathy, as determined by standard microscopy.

    This is the first time researchers have used high content analysis to show specific details of enterocyte morphology. Such an approach permits doctors to quantitatively analyze enterocyte intracellular structure from standard biopsy samples and allows for detection of minute changes that develop before the classic histological lesion.

    This process could become important for improving the diagnosis of celiac disease. If doctors can spot celiac-related intestinal lesions before they develop, they can begin to prevent celiac disease before it develops and thereby save lives.

    Central European Journal of Biology
    Volume 3, Number 3 / September, 2008


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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 "Cereal Killers" by Scott Adams and Ron Hoggan, Ed.D.

  • Related Articles

    Scott Adams
    Gene Ther 2003 May;10(10):835-43
    Londei M, Quaratino S, Maiuri L.
    Institute of Child Health, University College London, London, UK.
    Celiac.com 05/29/2003 - This highly technical and hopeful article covers the possibility of using gene therapy to one day cure celiac disease. Here are the introduction and final words:
    "Gene therapy (GT) is still at the experimental stage and some recent setbacks have cooled the potential use of this therapeutic tool even in life-threatening conditions. However, this therapeutic approach has a potential, which is not limited to disease for which we have not other option. There are increasing evidence that GT will be soon used in diseases that are not life threatening. One group of diseases that can benefit from GT is the autoimmune one. Several experimental animal models have indicated the efficacy (proof of principle) of GT. In the present review, we have addressed the possibility that even extremely benign autoimmune-like diseases such as Celiac Disease (celiac disease) might one day profit from this type of therapy. We further point that in conditions such as celiac disease, where the trigger is well known and the pathogenic cascade is relatively well defined, a situation not common in autoimmunity, we can even have a better situation where to explore and use GT to control disease initiation and progression. Once the risks that are still intrinsic to GT will have been reduced the therapeutic options we outline in the present review might not appear too far from reality."
    "celiac disease is the prototype of diseases in which a clear role of antigen-specific T cells has been demonstrated and where their inhibition results in disease amelioration. The present therapeutic approach is the removal of the antigenic challenge: the gluten-free diet, which is effective if there is a strict compliance to the diet. It is, however, not always easy to follow such strict restrictions for all life and alternative approaches have to be considered. The use of GT is at the moment a remote hypothesis as celiac disease is a relatively benign condition, with a valid therapeutic approach and GT has intrinsic risks that have been highlighted recently. The scope of this review is, however, to indicate a future application of GT when, as they will, the present limitations and intrinsic risks of GT will be overcome."


    Jefferson Adams
    Celiac.com 06/12/2009 - In a medical first, researchers at UCLA have made a connection between intestinal inflammation and systemic chromosome damage in mice, a discovery that may pave the way for early identification and treatment of human inflammatory disorders, some of which raise the risk for various kinds of cancer, according a study published in Cancer Research.
    Scientists discovered that local intestinal inflammation caused DNA damage to lymphocytes of the peripheral blood circulating throughout the body. So, contrary to conventional medical wisdom, chromosome damage is not limited to the immediate intestine, but involves body tissues far away from the actual inflammation. Their results showed single- and double-strand DNA breaks in the blood, and chromosome damage in peripheral blood indicating systemic genetic damage.
    Inflammatory diseases have been linked to some lymphomas and abdominal, liver and colorectal cancers, said Robert Schiestl, lead author, and professor of pathology, radiation oncology and environmental health sciences and a Jonsson Cancer Center scientist.
    Finding inflammation early – before any symptoms surface - and treating the associated causes quickly may prevent the damage that eventually triggers these cancers, he said. Before the study, researchers had no knowledge that "intestinal inflammation causes damage that can be found throughout the body,” said Schiestl, adding that this "may help explain how inflammation leads to these cancers.”
    Intestinal inflammation can be caused by such maladies as Crohn’s disease, inflammatory bowel disease, ulcerative colitis and Celiac disease. Nearly 1.5 million Americans, and 2.2 million Europeans currently suffer from inflammatory bowel diseases and global incidence is on the rise, Schiestl said.
    The discovery opens up the possibility of using chromosome damage in the peripheral circulating blood as a biomarker to spot intestinal inflammation before any symptoms surface.
    Researchers were able to detect chromosome damage in the blood of specially bred mice before the onset of colitis, said Aya Westbrook, a graduate student of the UCLA Molecular Toxicology Interdepartmental Program and the paper's first author. Westbrook added that disease severity correlated directly with higher levels of chromosome damage in the blood.
    Chromosome damage, according to study author Dr. Jonathan Braun, professor and chairman of the Department of Pathology and Laboratory Medicine at UCLA, may be the “earliest detectable indicator” of intestinal inflammatory disease. Currently, the only way to diagnose patients with inflammatory bowel disease is through full endoscopic exam, which is both invasive and costly. In theory, Braun said, a biomarker blood test might replace the invasive endoscopic exam and allow physicians to identify early inflammatory disease before it develops fully.
    Spotting disease and being able to ward it off early is one of the Holy Grails of all medicine. This breakthrough could “change the natural history of these diseases,” Braun said. For the first time, doctors might have a tool that can actually help spot inflammation, the earliest precursor to multiple kinds of cancer, at its earliest stages, long before any actual disease develops. This could lead to the prevention of tens of thousands of cancers.
    UCLA researchers have launched a clinical trial to confirm their findings in humans, Schiestl said. They’re focusing on patients with Crohn’s disease and ulcerative colitis. They're hoping the discovery will permit them to test new strategies for treating smoldering disease, which we’ve never been able to identify before,” Schiestl said, adding that they might be able to assess new drugs for treating early inflammatory disease.
    The research may also show why some patients with inflammatory disease develop cancers, while others endure chronic inflammation for decades, yet remain cancer-free. Researchers suspect that some unknown molecular mechanisms might work to protect some patients and not others. Finding such mechanisms might lead to tests for predicting which patients with intestinal inflammatory diseases are predisposed to cancer.
    Cancer Research: June 1 2009, Volume 69, Issue 11 

    Jefferson Adams
    Celiac.com 11/11/2009 - Although doctors view celiac disease mainly as a gastrointestinal disease, it is now known to have widespread systemic manifestations.
    A team of researchers recently set out to define the nature and role of systemic cytokine levels in the pathophysiology of celiac disease.  The research team was made up of John Sanil Manavalan, Lincoln Hernandez, Jayesh Girish Shah, John Konikkara, Afzal Jamal Naiyer, Anne Roland Lee, Edward Ciaccio, Maria Theresa Minaya, Peter H.R. Green, and Govind Bhagat of the Departments of Medicine and Pathology at Columbia University's College of Physicians and Surgeons.
    The team conducted multiplex cytokine assays on four different groups of adult patients: patients with active celiac disease; patients on a gluten-free diet with positive TTG IgA antibodies, patients on a gluten-free diet with negative antibodies; and those with refractory celiac disease.
    They then compared the results against the values in healthy adult controls.
    Patients with active celiac disease and those on gluten-free diet with positive antibodies showed substantially higher levels of pro-inflammatory cytokines, such as interferon-, interleukin (IL)–1, tumor necrosis factor–, IL-6 and IL-8, and also Th-2 cytokines such as IL-4 and IL-10, compared with normal controls and patients on a gluten-free diet without antibodies.
    One interesting finding was that patients following a gluten-free diet for under 1 year showed substantially higher levels of both pro-inflammatory cytokines and Th2 cytokines compared with the patients on gluten-free diet for more than 1 year.
    Moreover, the team noted a statistically significant association between levels of TTG IgA titers and serum levels of Th-2 cytokines IL-4 (p 0.001), IL-10 (p  0.001) and inflammatory cytokines such as IL-1 (p  0.001), IL-1 (p 0.005), and IL-8 (p  0.05).
    Journal of Human Immunology, 2009.
    j.humimm.2009.09.351


    Jefferson Adams
    Can Celiac Disease be Diagnosed without Intestinal Biopsy?
    Celiac.com 05/28/2013 - Is an intestinal biopsy always necessary to diagnose celiac disease, or can diagnosis be made without biopsy? To answer that question, a team of researchers recently set out to compare celiac disease–specific antibody tests to determine if they could replace jejunal biopsy in patients with a high pretest probability of celiac disease.
    The research team included Annemarie Bürgin-Wolff, Buser Mauro, and Hadziselimovic Faruk. They are variously affiliated with the Institute for Celiac Disease in Liestal, Switzerland, and Statistik Dr. M. Buser, Riehen, Switzerland.
    Their retrospective study included blood test data from 149 patients with celiac disease, along with 119 controls. All patients underwent intestinal biopsy, and all samples were analyzed for IgA and IgG antibodies against native gliadin (ngli) and deamidated gliadin peptides (dpgli), as well as for IgA antibodies against tissue transglutaminase and endomysium.
    They found that tests for dpgli were superior to ngli for IgG antibody determination: 68% vs. 92% specificity and 79% vs. 85% sensitivity for ngli and dpgli, respectively. Predictive values were also higher for dpgli than for ngli; positive (76% vs. 93%) and negative (72% vs. 83%).
    Regarding IgA gliadin antibody determination, sensitivity improved from 61% to 78% with dpgli, while specificity and positive predictive value remained at 97% (P less than 0.00001).
    A combination of four tests (IgA anti-dpgli, IgG anti-dpgli, IgA anti- tissue transglutaminase, and IgA anti-endomysium) yielded positive and negative predictive values of 99% and 100%, respectively and a likelihood ratio positive of 86 with a likelihood ratio negative of 0.00.
    Omitting the endomysium antibody determination still yielded positive and negative predictive values of 99% and 98%, respectively and a likelihood ratio positive of 87 with a likelihood ratio negative of 0.01.
    Conclusion: Antibody tests for dpgli yielded superior results compared with ngli. A combination of three or four antibody tests including IgA anti-tissue transglutaminase and/or IgA anti- endomysium enabled reliable diagnosis or exclusion of celiac disease without intestinal biopsy in 78 percent of patients.
    This two-step method of performing jejunal biopsy only in patients with discordant antibody results (22%) would catch all patients except those with no celiac-specific antibodies; who would then be caught through biopsy.
    Source:
    BMC Gastroenterol. 2013;13(19)

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