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Found 13 results

  1. Celiac.com 06/28/2017 - Tests to measure serum endomysial antibodies (EMA) and antibodies to tissue transglutaminase (tTG) were developed to screen for celiac disease in patients who are actively eating gluten. However, doctors often use them to monitor patients on a gluten-free diet. Now, making sure celiac patients are successfully following a gluten-free diet is important, as unconscious gluten ingestion can lead to complications over time. But how accurate are these tests for assessing gluten-free compliance in celiac patients? A team of researchers recently set out to assess the sensitivity and specificity of tTG IgA and EMA IgA assays in identifying patients with celiac disease who have persistent villous atrophy despite a gluten-free diet. The research team included Jocelyn A. Silvester, Satya Kurada, Andrea Szwajcer, Ciarán P. Kelly, Daniel A. Leffler, and Donald R. Duerksen. They are variously affiliated with the Farncombe Family Digestive Health Research Institute and Division of Gastroenterology, and the Department of Pathology and Molecular Medicine and Department of Medicine, McMaster University, Hamilton, Ontario. To begin their meta-analysis, the team searched PUBMED, EMBASE, BIOSIS, SCOPUS, clinicaltrials.gov, Science Citation Index, and Cochrane Library databases through November 2016. They included studies of subjects with biopsy-confirmed celiac disease, follow-up biopsies and measurement of serum antibodies on a gluten-free diet, biopsy performed on subjects regardless of symptoms or antibody test results. Their analysis excluded patients with refractory celiac disease, undergoing gluten challenge, or consuming a prescribed oats-containing gluten-free diet. They determined positive or negative findings based on manufacturer cut-off values. They defined villous atrophy a Marsh 3 lesion or villous height:crypt depth ratio below 3.0. They constructed forest plots to determine the sensitivity and specificity of detection for individual studies. For their meta-analysis, they used a bivariate random effects model to determine both sensitivity and specificity. Their search of abstracts revealed 5,408 unique citations, which yielded 442 articles for detailed review. Those reviewed articles yielded just 26 studies that met the team’s inclusion criteria (6 of tTG assays, 15 of EMA assays, and 5 of tTG and EMA assays). Inability to cross-tabulate histologic and serologic findings was the most common reason the team excluded a given study from analysis. They found that serum assays identified patients with persistent villous atrophy with high levels of specificity: 0.83 for the tTG IgA assay (95% CI, 0.79–0.87) and 0.91 for the EMA IgA assay (95% CI, 0.87–0.94). However, the tests showed low sensitivity for detecting villous atrophy: 0.50 for the tTG IgA assay (95% CI, 0.41–0.60) and 0.45 for the EMA IgA assay (95% CI, 0.34-0.57). Results were similar in both pediatric and adult patients. A meta-analysis of biopsy-confirmed celiac patients who received follow-up biopsy while on a gluten-free diet, showed that tests for serum tTG IgA and EMA IgA had low sensitivity, detecting persistent villous atrophy less than 50 percent of the time. The team supports the search for more accurate, non-invasive, markers of mucosal damage in celiac patients who follow a gluten-free diet. Source: Gastroenterology. DOI: http://dx.doi.org/10.1053/j.gastro.2017.05.015
  2. Celiac.com 01/26/2017 - The only currently effective therapy for celiac disease is for patients to follow a gluten-free diet. However, no serum marker for gluten intake has yet been found, so it's not always easy for doctors to tell if patients are following their diets properly. A team of researchers recently set out to evaluate the use of alkylresorcinol concentrations for detecting dietary gluten intake in humans and mice. The research team included R. S. Choung, J. A. Murray, E. V. Marietta, C. T. Van Dyke, and A. B. Ross. They are variously affiliated with the Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA, and with the Department of Biology and Biological Engineering, Chalmers University of Technology in Gothenburg, Sweden. For their study, they compared alkylresorcinol concentrations among 34 treated patients with celiac disease, 36 untreated celiac disease patients and 33 control subjects. They also evaluated seven additional celiac disease patients whose serum samples were available at diagnosis and after gluten-free diet. In mice, they compared alkylresorcinol concentrations in the serum of five mice fed a regular chow, and 10 mice fed lifelong with a gluten-free chow. In addition, They also assessed the effect of added gluten on alkylresorcinol concentrations. Their study indicates that serum alkylresorcinol concentrations could be a useful marker for dietary gluten in celiac disease. Certainly, having an easy, reliable way for doctors to spot dietary gluten will be useful in helping people with celiac disease maintain their required gluten-free diets. Source: Alimentary Pharmacology & Therapeutics. DOI: 10.1111/apt.13917
  3. Celiac.com 02/28/2008 - A study published in the Leukemia Research Journal (Volume 30, issue 12, Pages 1585-1586 - December 2006) looked at samples of serum from multiple myeloma patients. In 35% of the samples the myeloma monoclonal proteins had antigliadin activity, and migrated just like celiac anti-gliadin antibodies when subjected to electrophoresis. Monoclonal gammopathy (MGUS) is a precursor stage to multiple myeloma, with the same or very similar sort of monoclonal proteins as in multiple myeloma, and converts to it at the rate of about 1.5% per year. Therefore if one lives for 20 years after diagnosis with MGUS, one has a 30% chance of ending up with deadly, so far incurable, multiple myeloma, which is a cancer of the bone marrow and blood. For those diagnosed with MGUS it seems like a time bomb ticking, and each time one goes for the monitoring blood tests, there is some degree of anxiety. It was postulated by the researchers that multiple myeloma may actually be an end result of untreated celiac disease. This is why there has been a large reaction about this on the various MGUS web forums.Thirty-five percent is very high! At least one of our ChooseHope.com MGUS forum members was recently tested and found to have Celiac Disease and there are numerous other persons on the various MGUS forums alleging that they have this combination of conditions. In another publication from the database at PubMed.gov (Gut. 1976 Sep;17(9):735-9.), a study that showed that when a patient with MGUS and Celiac Disease was put on a gluten-free diet the monoclonal proteins entirely disappeared by the end of 3 years! Hence you can imagine what big news this is to all the MGUS patients, on the various online MGUS forums. Here is the suggestion that Celiacs might avoid becoming MGUS patients, that MGUS patients might perhaps avoid progression to multiple myeloma, and that multiple myeloma patients might have halted or slower progression of their disease, simply by being on a gluten-free diet! This is indeed big news! The ramifications of this are that everyone with Celiac Disease really should undergo testing for MGUS/Myeloma which can be associated with various autoimmune diseases, increased rate of osteoporosis, and neuropathy, or no symptoms at all! Likewise all MGUS patients should be tested for celiac disease, which again can be associated with various autoimmune diseases, increased rate of osteoporosis, and neuropathy, or no symptoms at all! Do you see the similarities? I am currently working on a letter to Blue Cross Blue Shield, informing them of the results of these studies and suggesting that their policy of reimbursing for celiac DNA testing of first degree relatives of known celiacs should be expanded to also include all persons having serum monoclonal proteins. This would include not just MGUS and multiple myeloma, but also Waldenstrom's macroglobulinemia. I would also like to call for intensified research on the link between celiac disease and paraproteinemia.
  4. Journal of Clinical Gastroenterology 2003; 36(3):219-221 Celiac.com 03/28/2003 - A study by Antonio Tursi, M.D, et al, was recently conducted to evaluate the correlation between the degree of histologic intestinal damage in celiac patients and their level of positivity (serum value) to anti-tissue transglutaminase antibodies (anti-tTG). The study looked at 119 adult celiac patients who were diagnosed consecutively (47 men and 72 women; mean age, 28 years; range, 22-51 years), and were stratified for histologic damage according to Marsh classification. The final step was to compare their Marsh histologic intestinal damage classification with their anti-tTG serum values. Here are their results: Marsh I lesions were present in 13 patients (10.92%), Marsh II in 24 anti-tTG (20.16%), Marsh IIIa in 27 anti-tTG (22.68%), Marsh IIIb in 31 anti-tTG (26.05%) and Marsh IIIc in 24 anti-tTG (20.16%). Anti-tTG positivity was ranging from 1 of 13 anti-tTG (7.69%) in Marsh I lesions to 23 of 24 anti-tTG (95.83%) in Marsh IIIc lesions respectively (P The researchers conclude that the mean serum value in celiacs with severe enteropathy (Marsh IIIb-c lesions) was higher than in those with only slight enteropathy (Marsh I-IIIa). Further, serologic test results in the absence of histologic evaluation (biopsy) may "underestimate the real prevalence of celiac disease," thus delaying a proper diagnosis and putting patients at risk for a large variety of serious health problems.
  5. Celiac.com 03/22/2013 - Enterocyte damage is one of the common features of celiac disease, and often results in malabsorption. Presently, doctors don't know very much about the recovery of enterocyte damage and its clinical consequences. Serum intestinal fatty acid binding protein (I-FABP) is a marker that allows researchers to study enterocyte damage. A research team set out to determine the severity of enterocyte damage in adult-onset celiac disease, how it responds to a gluten-free diet, and the correlation among enterocyte damage, celiac disease autoantibodies and histological abnormalities during the course of disease. The research team included M. P. M. Adriaanse, G. J. Tack, V. Lima Passos, J. G. M. C. Damoiseaux, M. W. J. Schreurs, K. van Wijck, R. G. Riedl, A. A. M. Masclee, W. A. Buurman, C. J. J. Mulder, and A. C. E. Vreugdenhil. They are affiliated with the Department of Paediatrics & Nutrition and Toxicology Research Institute Maastricht (NUTRIM) at Maastricht University Medical Centre in Maastricht, the Netherlands. For their study, the team first determined I-FABP blood levels in 96 biopsy-proven adults with celiac disease, and in 69 patients following a gluten-free diet. They used 141 individuals with normal antitissue transglutaminase antibody (IgA-tTG) levels as a control group. They found that levels of I-FABP were related to the degree of villous atrophy (Marsh grade) and IgA-tTG. Patients with untreated celiac disease showed higher I-FABP levels (median 691 pg/mL) compared with control subjects (median 178 pg/mL, P < 0.001) and correlated with Marsh grade (r = 0.265, P < 0.05) and IgA-tTG (r = 0.403, P < 0.01). I-FABP blood levels in patients following a gluten-free diet dropped substantially, but not within the range found in control subjects, even though they showed normalization of IgA-tTG levels and Marsh grade. Celiac patients with elevated I-FABP levels who did not respond to gluten-free diet showed persistent histological abnormalities. The team's main finding was that enterocyte damage, as assessed by serum I-FABP, correlates with the severity of villous atrophy in celiac disease at the time of diagnosis. Even though enterocyte damage improves upon treatment with a gluten-free diet, the majority of patients still show substantial enterocyte damage despite the absence of villous atrophy and low IgA-tTG levels. Thus, they conclude that elevated I-FABP levels that do not respond to a gluten-free diet likely point to histological abnormalities and warrant further evaluation. Source: Aliment Pharmacol Ther. 2013 Feb;37(4):482-90. doi: 10.1111/apt.12194.
  6. Celiac.com 01/04/2013 - Currently, doctors must still use invasive techniques to distinguish between uncomplicated and complicated forms of celiac disease. In an effort to find a non-invasive approach to the issue, a research team recently set out to investigate the potential use of novel serum parameters, including IL-6, IL-8, IL-17, IL-22, sCD25, sCD27, granzyme-B, sMICA and sCTLA-4 in patients diagnosed with active celiac disease, celiac disease on a GFD, Refractory coeliac disease (RCD) type I and II, and enteropathy associated T-cell lymphoma (EATL). The research team included Greetje J. Tack, Roy L. van Wanrooij, B. Mary Von Blomberg, Hedayat Amini, Veerle M. Coupe, Petra Bonnet, Chris J. Mulder and Marco W. Schreurs. Their investigation revealed elevated levels of the pro-inflammatory IL-8, IL-17 and sCD25 in both active celiac disease and in refractory celiac disease, types I and II. They also found that RCDII patients displayed higher serum levels of soluble granzyme-B and IL-6 in comparison to active celiac disease patients. Furthermore, EATL patients showed higher levels of IL-6 as compared to all other groups. Otherwise, the team found no differences between RCDI and active celiac disease or RCDII. These novel serum parameters show distinct immunological differences in RCDII and EATL, compared with uncomplicated celiac disease and RCDI. Source: BMC Gastroenterology 2012, 12:159. doi:10.1186/1471-230X-12-159
  7. Celiac.com 06/24/2010 - Scientists have previously seen a nuclear fluorescence reactivity (NFR) pattern on monkey esophagus in sections which were exposed to celiac disease patients that were sera positive for anti-endomysium antibodies (EMA). Because of this prior knowledge, scientists created a new study to illustrate the NFR, to study NFR positive results in connection with gluten withdrawal, and also to assess the possible role of NFR in celiac disease follow-up's. For twelve months, scientists closely evaluated twenty untreated celiac patients, eighty-seven treated celiac patients, and fifteen healthy control subjects. Scientists incubated the sera of all 122 patients on monkey esophagus sections. The goal was to evaluate the existence of NFR by indirect immunofluorescence analysis. To asses the rate of NFR in culture supernatants, duodenal mucosa samples from treated celiac patients were challenged with gliadin peptides. Scientists evaluated the reactivity of NFR immunoglobulins (Igs) response to the nuclear extract of human intestinal cells. What they found was that serum NFR was visible in all untreated celiac patients and it persisted for up to 151 +/-37 days from gluten withdrawal. It reappeared in treated celiac patents when they did not stick to their dietary restrictions. Serum NFR was also present in two of the healthy control subjects. NFR presented itself before EMA, in culture supernatants of celiac intestinal mucosa that was challenged with gliadin peptides. The Igs responsible for NFR were labeled as, “IgA2 Subclass”. The NFR had different results than the EMA and anti-nuclear antibodies, although they reacted with two nuclear antigens of 65 and 49 kDa. Thus, a new auto-antibody named NFR, which is related to celiac disease, was depicted. In conclusion, the studies of NFR have demonstrated that NFR detection has potential to be used as a beneficial tool in monitoring compliance of a gluten-free diet, as it has the ability to diagnose slight dietary shifts pertaining to gluten. Source: Clinical and Experimental Immunology
  8. 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
  9. Celiac.com 01/11/2007 – Researchers in Finland have determined that many patients with untreated celiac disease show the presence of intestinal endomysial autoantibodies (EmA), even in the 10-20% of cases where their serum EmA is negative. The researchers also believe that the negative serum EmA test in these cases is an indication of more advanced and long-standing celiac disease. Normally positive serum EmA is close to 100% accurate, however there is a subset of around 10-20% of patients where the test is negative even though they do have the disease. Dr. Katri Kaukinen and colleagues at the University of Tampere looked at 177 celiac disease patients and found that 22 were serum EmA-negative. A common theme among the 22 serum EmA-negative patients was that they were older and had more abdominal symptoms and other complications that indicated a more advanced stage of celiac disease than their serum EmA-positive counterparts. The research team found that even though the EmA antibodies could not be detected in the blood of these 22 patients, they could be detected in the small bowel mucosa in all of them, and none were detected in 20 control patients. Dr. Kaukinen and colleagues believe that the use of intestinal EmA antibody detection should be used in seronegative individuals who are suspected to have celiac disease. This study further supports Dr. Kenneth Fines use of IgA antigliadin antibodies in the stool to detect gluten sensitivity, and one has to wonder if the EmA antibodies, if detectable in the small bowel mucosa, would not also be detectable in the patient’s stool, and if so would that not be a much better and more cost-effective way to perform such a screening? Gut 2006;55:1746-1753.
  10. The following abstract was submitted to celiac.com directly by William Dickey, Ph.D., a leading celiac disease researcher and gastroenterologist who practices at Altnagelvin Hospital, Londonderry, Northern Ireland. Scandinavian Journal of Gastroenterology 2005; 40: 1240-3. Dickey W, Hughes DF, McMillan SA. Celiac.com 09/27/2005 - What does a positive endomysial antibody (EmA) test mean if the biopsy does not show villous atrophy? The authors studied 35 patients where this was the case. In the authors practice, these patients account for 10% of all EmA positives. Firstly, the lack of villous atrophy did not necessarily mean a normal biopsy: 14 patients had excess inflammatory cells (lymphocytes) consistent with a mild abnormality of gluten sensitivity. Secondly, many of these patients had typical celiac features: twelve had a family history of celiac, five had dermatitis herpetiformis and thirteen had osteopenia or osteoporosis on DEXA scan. After discussion, 27 patients opted to take a gluten-free diet from the first biopsy: 26 of these had clinical improvement. Seven of eight patients who persisted with a normal diet developed villous atrophy on follow-up biopsies. The authors conclude that a positive EmA result indicates gluten sensitivity even if biopsies do not show villous atrophy. While a biopsy remains important as a baseline reference, these patients should be offered a gluten-free diet to allow clinical improvement and prevent the development of villous atrophy. There may be no such thing as a "false positive" EmA, although the authors emphasise that the same conclusion cannot yet be applied to tissue transglutaminase antibody results.
  11. Eur J Gastroenterol Hepatol. 2002 Apr;14(4):425-7. Related Articles, Links Celiac.com 07/30/2004 - The following abstract of a study that was done in 2002 emphasizes the importance of vitamin supplementation in the treatment of many celiacs: Dickey W. - Department of Gastroenterology, Altnagelvin Hospital, Londonderry BT47 6SB, Northern Ireland. OBJECTIVE: Although coeliac disease is a disorder of the proximal small bowel, associated vitamin B12 deficiency has been reported. This study aimed to assess the prevalence of B12 deficiency in a large series of coeliac patients, and to exclude the possibility that it is due to associated autoimmune gastritis. DESIGN: Prospective routine measurement of serum B12 in coeliac patients, with investigations for pernicious anaemia/autoimmune gastritis in B12-deficient patients. SETTING: Gastroenterology department of a large district general hospital. INTERVENTIONS: If they were not taking vitamin B12 supplements already, patients had serum B12 measured before starting dietary gluten exclusion. Those with low levels also had gastric biopsies taken and plasma gastrin and serum gastric parietal cell and intrinsic factor antibodies measured. MAIN OUTCOME MEASURES: Prevalence of low serum B12, and presence or absence of indicators of pernicious anaemia/autoimmune gastritis in patients with low serum B12. RESULTS: Of 159 patients, 13 had low serum B12 at diagnosis. A further six had been receiving B12 replacement therapy for 3-37 years before diagnosis, giving an overall prevalence of 12% (19 patients). Only 2/19 patients had gastric corpus atrophy, one with intrinsic factor antibodies and the other with hypergastrinaemia. There was no relationship between low B12 and clinical characteristics. CONCLUSIONS: Low B12 is common in coeliac disease without concurrent pernicious anaemia, and may be a presenting manifestation. B12 status should be known before folic acid replacement is started.
  12. J Tropical Pediatrics 2004, 50:37-40 Celiac.com 03/30/2004 – Researchers in India have discovered that serum prolactin levels in those with celiac disease are elevated in direct proportion to the severity of the disease. Dr. Gaurav Kapur and colleagues from the Lady Hardinge Medical College, New Delhi screened serum prolactin levels in 41 children who were diagnosed with celiac disease, 21 of which were on a gluten-free diet for more than a year. The results were compared to 41 healthy controls. The researchers found that serum prolactin levels were highly elevated in those with active celiac disease (average of 48.3 ng/mL), and present at lower levels in those on a gluten-free diet (average of 18.3 ng/mL). The healthy controls had an average level of 9.3 ng/mL. The longer the disease was left untreated along with the increase in severity of villous atrophy, the higher the levels of serum prolactin that were detected. The researchers conclude that serum prolactin levels can be used to determine the severity of celiac disease in patients, and this option is more economically viable than the use of other options.
  13. Vijay Kumar, M.D., Research Associate Professor at the University of Buffalo and President and Director of IMMCO Diagnostics: The biopsy may be inconclusive. Serum, if tested for gliadin, endomysial and reticulin antibodies, should provide unequivocal information. Ours and other studies have provided a strong reliability of the serum tests. Karoly Horvath, M.D., Ph.D., Associate Professor of Pediatrics; Director, Peds GI & Nutrition Laboratory; University of Maryland at Baltimore: The biopsy may be inconclusive in a small percentage of patients with so-called patchy lesions in the duodenum. It means that there are histologically normal looking spots with finger like villi and pathologic spots showing flattened mucosa in the upper half of the duodenum. If celiac disease is suspected, the gastroenterologist should obtain several biopsies from different spots of the whole duodenum. Most of the endoscopists routinely examine only the upper half of the duodenum (duodenal bulb and the descending part). The transverse segment of the duodenum is not viewed routinely. Few endoscopic centers have an enteroscope, which is a longer and more flexible endoscope for examining the entire duodenum and jejunum. The enteroscopy allows you to obtain biopsies even from the jejunum. The histological examination of a single biopsy specimen may increases the risk of false negative diagnosis. The experience of the pathologist in the interpretation of small intestinal histology is important. In centers specializing in celiac disease the gastroenterologist routinely reviews the histologic slides together with the pathologist. There is still a possibility of inconclusive results if multiple biopsies are obtained and the histological interpretation is appropriate. All disease has a developmental process. It means that it takes time for the pathological changes to be evident. There are cases when the symptoms suggest celiac disease, however, the histology is not conclusive. This problem occurs in only a few cases. A repeated biopsy may be necessary after a period of higher gluten intake. However, if the antiendomysium antibody test is positive and the histology is not conclusive a gluten-free diet is recommended. The serology test may be inconclusive if: The sample handling and shipping is inappropriate; e.g. the serum was shipped at room temperature for days The patient has IgA deficiency, which occurs in one out of 600 people in the general population and much more frequently in patients with celiac disease. In these cases the antigliadin IgA and the antiendomysium IgA tests give negative results. If the tests are performed in a laboratory specialized in celiac serological tests, the laboratory recommends a test for immunoglobulins. If a patient has IgA deficiency and positive antigliadin IgG test, he/she should undergo further absorptive tests and/or an intestinal biopsy.
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