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Celiac.com 09/27/2023 - A team of researchers recently set out to explore duodenal villous atrophy in adults with suspected celiac disease without IgA deficiency. The research team included Prof Carolina Ciacci, MD, Prof Julio Cesar Bai, MD, Geoffrey Holmes, MD, Abdulbaqi Al-Toma, MD, Prof Federico Biagi, MD, Prof Antonio Carroccio, MD, Rachele Ciccocioppo, MD, Prof Antonio Di Sabatino, MD, Rachel Gingold-Belfer, MD, Mariana Jinga, MD, Prof Govind Makharia, MD, Sonia Niveloni, MD, Gary L Norman, PhD, Kamran Rostami, MD, Prof David S Sanders, MD, Edgardo Smecuol, MD, Vincenzo Villanacci, MD, Santiago Vivas, MD, and Fabiana Zingone, MD, on behalf of theBi.A.CeD study group. The team conducted a multi-center, prospective cohort study to assess the accuracy of serum anti-tissue transglutaminase IgA (tTG-IgA) in diagnosing celiac disease in adults. The study included adult participants aged 18 years or older, with suspected celiac disease, who were not on a gluten-free diet, and did not have IgA deficiency. The participants were enrolled from 14 tertiary referral centers across different regions from February 27, 2018, to December 24, 2020. The main objective was to determine whether serum tTG-IgA tests could reliably diagnose celiac disease based on duodenal villous atrophy. The study included 436 participants (296 women and 140 men) with complete data on serum tTG-IgA and duodenal histology. Of these, 363 participants had positive serum tTG-IgA results, and 73 had negative results. After local review, it was found that 341 of the participants with positive serum tTG-IgA had positive histology (true positives), while 22 had negative histology (false positives). Among the 73 participants with negative serum tTG-IgA, seven had positive histology (false negatives), and 66 had negative histology (true negatives) after local review. Study Findings: Positive Predictive Value of 95.9% for Celiac Disease Serum tTG-IgA The study's findings showed a positive predictive value of 93.9% and a negative predictive value of 90.4% for serum tTG-IgA in diagnosing celiac disease. The sensitivity was 98.0%, indicating the test's ability to correctly identify true positive cases, while the specificity was 75.0%. After central re-evaluation of duodenal histology in discordant cases, the positive predictive value increased to 95.9%, and specificity improved to 81.5%. The sensitivity remained high at 98.0%. The study also found that the positive predictive value of serum tTG-IgA increased as the serological threshold was defined at higher multiples of the upper limit of normal (ULN). The area under the receiver operating characteristic curve (AUC) for serum tTG-IgA was 0.87 for the categorical definition (positive vs. negative) and 0.93 for the numerical definition (multiples of the ULN) in predicting duodenal villous atrophy. Conclusion Based on the data, the study suggests that in adults with a reliable suspicion of celiac disease and high serum tTG-IgA levels, a biopsy may reasonably be avoided in the diagnostic process. This information can be valuable in improving the efficiency and accuracy of diagnosing celiac disease in certain cases, reducing the need for biopsy. Read more in The Lancet Gastroenterology and Hepatology Note: The researchers are variously affiliated with the Department of Medicine, Surgery, and Dentistry, Scuola Medica Salernitana, University of Salerno, Salerno, Italy; the Research Institutes, Universidad del Salvador, Buenos Aires, Argentina; the Small Bowel Section, Dr C Bonorino Udaondo Gastroenterology Hospital, Buenos Aires, Argentina; Department of Gastroenterology, Royal Derby Hospital, Derby, UK; the Department of Gastroenterology and Hepatology, St Antonius Hospital, Nieuwegein, Netherlands; the Department of Internal Medicine and Medical Therapy, San Matteo Hospital Foundation, University of Pavia, Pavia, Italy; the Gastroenterology Unit of Pavia Institute, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy; the Unit of Internal Medicine, Cervello Hospital, University of Palermo, Palermo, Italy; the Gastroenterology Division, Rabin Medical Centre, Beilinson Hospital, Petah Tikva, Israel; the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; the Gastroenterology Department, Carol Davila University of Medicine and Pharmacy, Central Military Emergency University Hospital, Bucharest, Romania; the Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India; the Research and Development, Headquarters and Technology Centre for Autoimmunity, Werfen, San Diego, CA, USA; the Gastroenterology Unit, MidCentral DHB, Palmerston North, New Zealand; the Academic Unit of Gastroenterology, Sheffield Teaching Hospital NHS Foundation Trust, Sheffield, UK; the Institute of Pathology, Spedali Civili University of Brescia, Brescia, Italy; the Gastroenterology Unit, University Hospital of Leon, Leon, Spain; and the Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy, on behalf of the Bi.A.CeD study group.

Celiac.com 10/19/2021 - There is some data to indicate a connection between celiac disease and IgA nephropathy (IgAN). In celiac disease IgA-class tissue transglutaminase (tTG) autoantibodies are seen in the small bowel mucosa and extraintestinal organs, in addition to circulating in serum. A team of researchers recently studied whether celiac disease-type IgA-tTG deposits occur in kidney biopsies in a case series of IgAN patients with or without celiac disease. The research team included Rakel Nurmi, Ilma Korponay-Szabó, Kaija Laurila, Heini Huhtala, Onni Niemelä, Jukka Mustonen, Satu Mäkelä, Katri Kaukinen, and Katri Lindfors. They are variously affiliated with the Celiac Disease Research Center, Faculty of Medicine and Health Technology, Tampere University in Tampere, Finland; the Celiac Disease Center, Heim Pál National Pediatric Institute in Budapest, Hungary; the Department of Pediatrics, Faculty of Medicine and Clinical Center, University of Debrecen in Debrecen, Hungary; the Faculty of Social Sciences, Tampere University in Tampere, Finland; the Medical Research Unit, Seinäjoki Central Hospital in Seinäjoki, Finland; and the Department of Internal Medicine, Tampere University Hospital in Tampere, Finland The team looked at nine IgAN patients, four of whom had celiac disease. The team measured serum tTG autoantibodies at the time of the diagnostic kidney biopsy, and looked at colocalization of IgA and tTG in the frozen kidney biopsies. The results showed IgA-tTG deposits in the kidneys of three IgAN patients with celiac disease though two patients had been diagnosed with celiac disease years later. They fund no deposits in a known celiac disease patient who was following a gluten-free diet. Of the five non-celiac IgAN patients, three showed IgA-tTG deposits in their kidneys. From their small study, the team concludes that tTG-targeted IgA deposits can be found in the kidney biopsies of gluten-consuming IgAN patients, but they likely won't be much help in spotting celiac disease, due to limited specificity. Read more in Nutrients

Celiac.com 08/12/2020 - The interaction between celiac disease and the liver is complex and not well understood. In some cases, isolated hypertransaminasemia is the only clear sign of celiac disease, while in other cases, liver diseases can occur with isolated tissue transglutaminase antibodies IgA (tTG IgA), but without the histologic markers that would indicate celiac disease. A team of researchers recently set out to assess the results of tTG IgA testing for chronic liver disease (CLD) or cytolysis, and to seek out biopsy-confirmed celiac disease in patients with existing liver disease. The research team included Lena Cvetkovic, Gabriel Bernard, Nathanaelle Galette, Pierre-Olivier Hétu, Catherine Vincent, Mickael Bouin, and Amelie Therrien. They are variously affiliated with the Department of Medicine - Division of Gastroenterology, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; the Department of Biochemistry, Centre de recherche du Centre Hospitalier de l'Université de Montréal, Montréal, Québec, Canada; and the Department of Medicine, Division of Hepatology, Centre de recherche du Centre Hospitalier de l'Université de Montréal in Montréal, Québec, Canada. Their retrospective study used two groups. The first included 444 consecutive patients with no known celiac disease, for whom liver specialists had ordered tTG IgA testing. In this group, the team assessed the incidence of positive tTG and biopsy-confirmed celiac disease. The second group included 212 consecutive individuals with positive tTG IgA and subsequent duodenal biopsies. In this group, the team assessed the frequency and clinical features of patients without biopsy-confirmed celiac disease, both with and without liver disease. Tests conducted on the first patient group by a liver specialist turned up nine first time positive tTG IgA results. However, only six of these patients had biopsy-confirmed celiac disease. The second group included 33 individuals who also had liver disease, though nearly 43% showed no biopsy-confirmed celiac disease, compared with the 16% of patients who did not have liver disease. Nearly two-thirds of the patients without biopsy-confirmed celiac disease showed an increase below three times the upper limit of normal of tTG IgA. Cases of chronic liver disease without elevated transaminase levels showed no association with celiac disease. Testing liver disease patients for celiac disease can be helpful, but large numbers of patients may show positive celiac tests without any histological signs celiac disease. Read more at J Can Assoc Gastroenterol. 2020 Aug;3(4):185-193.

Celiac.com 11/11/2017 - (NOTE: This article is from 2012 and is being made available as Celiac.com rolls our past issues of Journal of Gluten Sensitivity) It's just like being a little kid with a super sore throat and your mom taking you to the doctor to get a test for strep throat. The doctor swabs your throat with two sticks to find out what nasty bacteria is camping out. In just moments you've got a diagnosis of strep throat and can start antibiotics to miraculously make the pain go away. You go home with a prescription, get in bed and eat mom's homemade chicken rice soup until you feel better in a couple of days. How cool would it be if getting diagnosed with celiac disease was this easy? The wonderful news is that we're getting closer to having a test that will diagnose celiac disease with just a simple prick of a finger and a 10-minute wait. The CeliacSure Test Kit measures (anti-tTG) IGA antibodies from a fingertip blood sample. It works by taking a small drop of blood, mixing it with a buffer and applying the mixture onto a test cartridge. Within moments two red lines appear if the test is positive, while only one line appears if the result is negative. And, you can take the test at home without ever getting out of your pajamas! "The test kit is a point-of-care, at-home test that's very similar to reading results of a pregnancy test," said Dr. Daniel Leffler of the Celiac Disease Center at Beth Israel Deaconess Medical Center in Boston. Dr. Leffler, a gastroenterologist by training with a background in nutrition, has a long-standing interest in celiac disease. Several years ago he teamed up with Dr. Ciaran Kelly and Dietitian Melinda Dennis to found the Celiac Disease Center at Beth Israel Deaconess Medical Center where they focus not only on providing top notch patient care, but also on high level disease research. The latest project: studying the efficacy of the CeliacSure test for celiac disease diagnosis. Dr. Leffler said his team got involved with the finger prick test study because they feel it's important to take down barriers to patients getting diagnosed with celiac disease. "We do a lot with educating other medical providers about offering in-clinic testing, but I think it's really important to put a tool in the hands of the people." "We've teamed up with the [marketers] of the test kit at GlutenPro/Biocard CeliacSure Test to see how effective this test is in the USA. We're providing 2 kits per family to use on first-degree relatives of people with celiac disease. To qualify, participants in the study must not be on a gluten-free diet. We send them the test kit to take as well as a survey about their ability to use and understand the test. The goal is that this small study comes out favorable [sic] so we can move on to large scale studies that will compare the finger prick test to the gold standard laboratory serology testing." Dr. Leffler says he's really excited about the potential of this point-of-care test because it will "allow us to reach a population that might not otherwise come in to get tested, mainly first degree relatives of patients already diagnosed with celiac disease." It's important to note that right now the CeliacSure test is only for research purposes, not actual diagnosis. It is available in Canada and other countries, but it's still under evaluation here in the United States. And, while the strep throat analogy is a great way to think about how this test will work, it's extremely important to understand that if you get a positive result with the CeliacSure test, do not start a gluten-free diet until you have followed up with a doctor to confirm the diagnosis. As with all medical studies there's some fine print you need to know about. Participants in the study must meet all of the following criteria: 1. Over the age of 18 2. A first or second degree relative with celiac disease 3. Not previously diagnosed with celiac disease 4. Not on a gluten-free diet or low-gluten diet within the past 3 months 5. Able and willing to self administer the test, complete a short survey form and return both in the envelope provided 6. Willingness to have follow up medical evaluation in the event of a positive test 7. A resident of the United States Listen to a full interview with Dr. Leffler about the CeliacSure study on the Hold the Gluten Podcast (http://traffic.libsyn.com/holdthegluten/050_HoldTheGluten-05Apr2012.mp3) with Vanessa Maltin Weisbrod and Maureen Stanley now! And, if you would like to participate in the study, please contact Dr. Toufic Kabbani at celiac@bidmc.harvard.edu or by phone at 617-667-0528.

Celiac.com 10/13/2017 - Tissue transglutaminase (tTG) immunoglobulin A (IgA) testing is a sensitive adjunct to the diagnosis of coeliac disease. The threshold for positivity was developed for diagnosis, with negative results reported as below the reference value (<4 U/mL). A team of researchers recently set out to investigate if an undetectable tissue transglutaminase IgA antibodies (tTG IgA<1.2 U/mL) is more predictive of healing compared to patients with negative but detectable serology (1.2-3.9 U/mL). The research team included H. Fang, K. S. King, J. J. Larson, M. R. Snyder, T. T. Wu, M. J. Gandhi, and J. A. Murray. They are variously affiliated with the Department of Medicine, the Division of Gastroenterology and Hepatology, the Division of Anatomic Pathology, the Division of Clinical Biochemistry and Immunology, the Division of Biomedical Statistics and Informatics, and the Division of Transfusion Medicine at the Mayo Clinic, Rochester, MN, USA. The research team conducted a retrospective study of 402 treated coeliac disease patients seen at the Mayo Clinic with negative tTG IgA values drawn within 1 month of duodenal biopsy between January 2009 and December 2015. The team used Corazza-Villanacci scores to assess mucosal healing, and logistic regression to assess the relationship of clinical variables with a normal biopsy. They also noted the presence of gastrointestinal symptoms. Their results showed that patients with undetectable test levels more frequently had normal duodenal histology, as compared with patients with detectable tTG IgA levels. Asymptomatic patients more often showed normal duodenal histology as compared to symptomatic patients. Patients with undetectable blood levels, and who followed a gluten-free diet for ≥2 years were more likely to have no villous atrophy, as compared to patients with detectable blood levels. Follow-up biopsies revealed that people recovering from celiac disease with negative tTG IgA serology showed that undetectable test levels are associated with normal histology. Source: AP&T