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Celiac.com 02/22/2021 - The skin has long been thought to be the body's largest organ. Recently, however, researchers discovered that the largest organ might actually be the interstitium, which lies just beneath the skin's outermost layers. It is that interstitial tissue that is the focus of a new biometric skin patch that may eventually diagnose numerous ailments faster and easier, and more cleanly than traditional blood tests. However, this is no easy task, as the interstitial tissue won't give up its secrets easily. Even though it's close to the skin, and close to blood, getting enough useful fluid from the interstitial tissue to get accurate test data is a bit like squeezing blood from a stone. Getting even a thousandth of a tablespoon, an amount still hundreds of times smaller than a standard blood draw, remains a challenge. A new development might offer a way around that challenge. In a recent paper, researchers at Washington University in St. Louis report using disposable micro-needle patches to capture ISF biomarkers, and to measure them up to about 800 times greater sensitivity than comparable biomarker tests. The thin rectangular patches contain hundreds of plastic micro-needles, each less than a millimeter long. To use them, simply press the patch against your finger, then dip the patch into a liquid solution of nanoparticles, which will sense and reveal presence of the certain known proteins. Because blood based testing can present logistical and financial challenges for poor and/or rural populations, such a test represents a logistical, scientific and financial breakthrough. "Currently, the new skin patches work on just a few biomarkers, but by significantly improving the sensitivity of immunoassays,” says Srikanth Singamaneni, a materials scientist who led the study, researchers may be able to help to meet the "need for bio-diagnostics in low- and middle-income countries—and even in rural parts of the United States.” The test can detect cytokine IL-6, and research has shown that detecting cytokines may be the best way to diagnose gluten sensitivity. A cheap, portable, reliable test that could spot celiac disease, gluten sensitivity and other health conditions, could be a major benefit to large numbers of people who remain undiagnosed, and for whom traditional blood tests are often out of reach. The team's data appears in Nature Biomedical Engineering. Read more on this in an excellent article by Wired.com

For immediate release. Please post. Celiac.com 07/13/2010 - Writer, researcher, and celiac advocate, Dr. Ron Hoggan, Ed. D., and long-time celiac advocate Scott Adams, founder and owner of Celiac.com, the largest and longest running website that caters to the gluten-free lifestyle, have joined forces to bring you a new, broad spectrum book about the many facets of gluten-induced illnesses and how to avoid or reverse them. In their new book, Hoggan, Adams, and their 27 co-authors reveal many of the hidden secrets of this widespread, insidious health hazard. This is more than a book about celiac disease and gluten sensitivity. It is a how-to manual for getting a diagnosis, reversing symptoms, improving one’s health, and living well on a gluten-free diet. Cereal Killers: Celiac Disease and Gluten-Free A to Z is a new resource that provides the most diverse exploration of this topic currently available. From the research scientist to the concerned parent, all voices are heard in this novel approach to curing gluten-induced ailments. There is information here for all levels of interest in this burgeoning new area of research and health care. "Hoggan & Adams have brought together a wide range of viewpoints at multiple levels. This book should appeal to a broad spectrum of readers who want a full and enriched perspective." --Robert Machon, July 12, 2010 Newly diagnosed celiac and gluten sensitive patients complain about conflicting information, from the safety of oats to the hazards of older grains. Cereal Killers has the answers to these and many other questions. Even seasoned members of the gluten-free community want a better understanding of their illness and the bounds of a safe diet. These questions are also addressed. Common errors, common misconceptions about the diet, and unusual insights into the dynamics of inflammation, disease, and recovery are all offered by one or more of the many voices that form this unique offering. But the information runs much deeper than that. Cereal Killers explores subtle nuances of immune reactions, often overlooked signs and symptoms of celiac disease, and a host of elements of associated illnesses that miraculously clear up on the diet. Questions about non-celiac gluten sensitivity are addressed in detail, along with explorations of what signs and symptoms should signal testing for gluten sensitivity and how much credence these indicators of disease should be given. In all, readers are offered a rich resource for understanding the importance of dietary compliance along with the cracks in the system through which patients sometimes slip because of current deficiencies in the understanding of gluten sensitivity and celiac disease. Jointly published by CreateSpace, Cereal Killers ISBN: 978-1449918200 is available through Celiac.com, and quality book sellers such as Blackbond Books.

Celiac.com 02/13/2019 - Microsoft and Adaptive Biotechnologies have announced a major milestone in their efforts to develop a blood test capable of diagnosing numerous diseases with a single blood sample. The companies are attempting to use data to map the immune system’s response to perceived threats. By cataloging the body’s immune responses to certain threats, and how those responses are reflected in the blood, they hope to create a single test to diagnose numerous diseases, including type 1 diabetes, celiac disease, ovarian cancer, pancreatic cancer and Lyme disease. To do this, they need huge amounts of data, and massive computing power for data sorting. The team’s artificial intelligence programs are central to their data crunching efforts. The team announced recently that the AI systems central to their task are now operational. Using that AI power, Adaptive and Microsoft are hoping to sequence immune data from 25,000 people with the five diseases by recruiting voluntary collaborators worldwide. Through the collaboration, they hope to collect information on how the T cells and white blood cells, central to the human immune response, bind to antigens. Once they’ve done that, the team hopes to develop methods for accurately diagnosing people with a given disease, or who have higher genetic risk for that disease. “Our AI systems are now ready. So please join us in decoding what ‘story’ the immune system is telling us,” wrote Peter Lee, Microsoft Corporate VP of AI and Research, on Twitter. Adaptive is working with the University of Florida, the Fred Hutchinson Cancer Research Center, and the University of Colorado and Virginia Mason, to profile thousands of people with type 1 diabetes, celiac disease, ovarian cancer, pancreatic cancer and Lyme disease, or with higher genetic risk factors for those diseases. Learn more about joining this scientific breakthrough at Adaptivebiotech.com

Celiac.com 12/03/2018 - Biomarkers in blood samples are not effective indicators for diagnosis or monitoring of celiac disease. A team of researchers recently set out to assess biomarkers of celiac disease derived from neoepitopes of deamidated gliadin peptides (DGP) and tTG fragments, and to assess their usefulness in identifying patients with celiac disease with mucosal healing. The research team included RS Choung, SK Rostamkolaei, JM Ju, EV Marietta, CT Van Dyke, JJ Rajasekaran, V Jayaraman, T Wang, K Bei, KE Rajasekaran, K Krishna, HK Krishnamurthy, and JA Murray. They are variously affiliated with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA; Vibrant Sciences LLC, San Carlos, CA, USA; and with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA. The team began by analyzing serum samples from 90 patients with biopsy-proven celiac disease, along with 79 healthy control subjects for immune reactivity against the tTG-DGP complex. They used a fluorescent peptide microarray platform to estimate the antibody binding intensity of each synthesized tTG-DGP epitope. They validated results in 82 patients with newly diagnosed celiac disease, and in 217 control subjects. They assessed the ability of the peptide panel to spot patients with mucosal healing based on histologic results and using serum samples from 85 patients with treated and healed celiac disease; 81 patients with treated but unhealed celiac disease who showed villous atrophy despite adhering to a gluten-free diet; 82 patients with untreated celiac disease; 27 disease control subjects who showed villous atrophy without celiac disease; and 217 healthy control subjects. To assess their data, they relied on principal component analysis followed by machine learning and support vector machine modeling. In all, the team found 172 immunogenic epitopes of the tTG-DGP complex. Compared with control subjects, celiac patients showed substantially higher immune reactivity against these epitopes. In the test group, neoepitopes derived from the tTG-DGP complex identified people with celiac disease with a remarkable 99% sensitivity and 100% specificity. Blood samples from untreated celiac patients showed the greatest average antibody-binding intensity against the tTG-DGP complex. Blood from patients with treated but unhealed CeD mucosa (15.1 ± 7.5) showed significantly higher average antibody-binding intensity than blood from patients with treated and healed CeD mucosa (5.5±3.4) (P<.001). The test spotted celiac patients with healing mucosa with 84% sensitivity and 95% specificity. The research team discovered immunogenic epitopes of the tTG-DGP complex, and found that a test that measures immune response to epitopes accurately identified both celiac patients and patients with mucosal healing. From this study, the team concludes that the biomarker method for celiac testing could be useful in both the detection and monitoring of celiac disease. Read more at: Gastroenterology.

Celiac.com 06/03/2010 - Clinical presentation of celiac disease can vary considerably from patient to patient. Most patients with celiac disease present atypical symptoms. Moreover, most patients who present abdominal symptoms in primary care do not have celiac disease, and so diagnostic tests for celiac disease are not necessary and should be avoided. A team of researchers recently conducted a systematic review of diagnostic testing for celiac disease among patients with abdominal symptoms. The team included Daniëlle A. W. M. van der Windt, PhD; Petra Jellema, PhD; Chris J. Mulder, MD, PhD; C. M. Frank Kneepkens, MD, PhD; and Henriëtte E. van der Horst, MD, PhD. Their article appears in the Journal of the American Medical Association. The goal of the research was to review and summarize evidence on the performance of diagnostic tests for spotting celiac disease in adults who present abdominal symptoms in primary care or similar settings. To obtain initial data, the team search MEDLINE (from January 1966 through December 2009, and EMBASE from January 1947 through December 2009. They also conducted a physical search of references for additional relevant studies. The team chose cohort or nested case-control diagnostic studies which included adults presenting non-acute abdominal symptoms, which featured celiac disease prevalence of 15% or less, and in which the tests included gastrointestinal symptoms or serum antibody screens. Two independent reviewers conducted studies tool and data extraction. They then calculated sensitivities and specificities for each study and computed pooled estimates using bivariate analysis where there was clinical and statistical homogeneity. In all, the team included sixteen studies encompassing 6085 cases in their review. Specificity, sensitivity, and confidence intervals for predicting celiac disease varied with abdominal symptoms. For patients presenting with classic diarrhea, for example, predictive sensitivity ranged from 0.27 to 0.86, while specificity ranged from 0.21 to 0.86. Pool estimates for 8 studies on IgA antiendomysial antibodies were 0.90, with a 95% confidence interval [CI] (0.80-0.95) for sensitivity and 0.99, with a 95% CI (0.98-1.00) for specificity, with a positive likelihood ratio [LR] of 171 and negative LR of 0.11. Pool estimates for IgA antitissue transglutaminase antibodies (7 studies) were 0.89, with a 95% CI (0.82-0.94) and 0.98 at 95% CI (0.95-0.99), respectively, with a positive LR of 37.7 and negative LR of 0.11. IgA and IgG antigliadin antibodies showed variable results, especially for sensitivity, which ranged from 0.46-0.87 for IgA, and from 0.25-0.93 for IgG. One recent study using deamidated gliadin peptides showed good specificity (0.94), but the target population offered limited supporting evidence. For adults who present abdominal symptoms in primary care or other unscreened settings, IgA antitissue transglutaminase antibodies and IgA antiendomysial antibodies offer high sensitivity and specificity for diagnosing celiac disease. SOURCE: JAMA. 2010;303(17):1738-1746. doi:10.1001/jama.2010.549

Celiac.com 05/21/2010 - Celiac disease is a genetic, permanent auto-immune disease with a variety of symptoms which, when treated with a gluten-free diet, usually subside. While clinical presentation is variable, most patients that are treated for abdominal pain do not have celiac disease. It is therefore important to accurately diagnose celiac disease in patients exhibiting abdominal pain, without unnecessarily testing patients that do not have celiac disease. Researchers at the Arthritis Research UK National Primary Care Centre, Primary Care Sciences, Keele University, Keele, Staffordshire ST5 5 BG, UK, evaluated sixteen studies of patients exhibiting abdominal pain. The occurrence of the abdominal symptoms varied vastly including the varied sensitivity of diarrhea. The IgA and IgG antigliadin antibodies exhibited varying results, particularly for sensitivity. A recent study used diamidated gliadin peptides and showed good specificity, but the results were limited in that specific target population. The conclusive results showed that among adult patients exhibiting abdominal symptoms, “IgA antitissue transglutaminase antibodies and IgA antiendomysial antibodies have high sensitivity and specificity for diagnosing celiac disease”. Source: JAMA. 2010 May 5;303(17):1738-46. Review.

Celiac.com 04/27/2010 - A team of clinicians recently assessed the diagnostic value of confocal endomicroscopy in celiac disease. Clinicians U. Günther, S. Daum, F. Heller, M. Schumann, C. Loddenkemper, M. Grünbaum, M. Zeitz, and C. Bojarski made up the research team. They are variously affiliated with the Medical Clinic of Gastroenterology, Rheumatology and Infectious Diseases, and with the Department of Pathology, Charité of the Campus Benjamin Franklin of University Medicine Berlin, Germany. Studies by Gutschmidt, by Henker and others have shown that, even in the face of greater awareness and more widespread blood testing, a number of countries suffer from low rates of celiac disease detection. Patchiness of the mucosal and submucosal changes associated with celiac disease impedes proper celiac diagnosis, and contributes to a small, but important sampling error among those assessed. Some clinicians feel that the problem might be resolved somewhat by modifying the endoscopic screening process to include real-time assessment of the duodenal morphology. Better endoscopic and imaging procedures will mean better diagnostic accuracy of biopsy specimens. One early step toward improved gathering of targeted biopsies in celiac disease patients lies in using magnification endoscopy, either alone, or together with high-resolution narrow-band imaging. This method offers better ability to detect patchy villous atrophy sites in the duodenum. However, neither magnification, nor narrow-band imaging techniques can detect increased number of intraepithelial lymphocytes (IELs). Confocal endomicroscopy (CEM) permits live, real-time histology with a 1000x magnification during endoscopy. Recently, a prospective pilot study for the first time showed CEM to enable effective live, real-time diagnosis and evaluation of celiac disease. Researchers compared endomicroscopic findings during live, real-time endoscopy with histological findings graded according to Marsh classification. The research team used CEM to examine twenty-four patients with celiac disease and six patients with refractory celiac disease, all following a gluten-free diet. The team evaluated duodenal mucosa by CEM and by conventional histological analysis for villous atrophy, crypt hyperplasia, and increased numbers of intraepithelial lymphocytes (IELs > 40/100 enterocytes). They then compared the CEM to the histology results for sensitivity, specificity, and inter-observer variability using Marsh classification scores. As control subjects, the team used thirty patients without celiac disease, but who were undergoing routine upper gastrointestinal endoscopy. Using conventional histology on the 30 patients with celiac disease, the team found 23 cases with villous atrophy and crypt hyperplasia, and 27 cases of increased IELs. Using CEM, the team found 17 cases of villous atrophy, 12 cases of crypt hyperplasia, and 22 cases of increased IELs. The CEM results compared favorably to those of conventional histology for villous atrophy, for which CEM showed a sensitivity of 74%, and for increased numbers of IELs, for which CEM showed a sensitivity of 81%. However, the CEM results were lacking for detecting crypt hyperplasia, for which CEM showed a sensitivity of 52%. The κ values for determination of inter-observer variability were 0.90 for villous atrophy, 1.00 for crypt hyperplasia, and 0.84 for IEL detection. For the 30 control patients, both traditional histology and CEM revealed normal duodenal architecture with overall specificity of 100%. From these results, the team concluded that the assessment of duodenal histology by CEM in patients with celiac disease is sensitive and specific in determining increased numbers of IELs and villous atrophy, but inadequate for detecting crypt hyperplasia. Until improvements are made, CEM is not suitable for use in diagnosing celiac disease. SOURCE: Endoscopy 2010; 42:197–202.