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Celiac.com 01/20/2024 - The tissue transglutaminase IgA antibodies (tTG-IgA) test is a crucial diagnostic tool for celiac disease. In individuals with celiac disease, the ingestion of gluten triggers an immune response, leading to the production of antibodies, including tTG-IgA. These antibodies target the tissues of the small intestine, causing damage and inflammation. The tTG-IgA test measures the levels of these specific antibodies in the blood. Elevated tTG-IgA levels are indicative of an active immune response to gluten and suggest the presence of celiac disease. This blood test is an essential component of the diagnostic process, helping healthcare providers identify individuals who may require further evaluation, such as genetic testing and an endoscopic biopsy, to confirm the diagnosis of celiac disease. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) are primarily associated with celiac disease, but they can also be elevated in some other conditions. It's important to note that the presence of elevated antibodies alone doesn't diagnose a specific condition, and further clinical evaluation is needed. Conditions and factors that may lead to elevated tTG-IgA antibodies may include the following: Non-Celiac Gluten Sensitivity (NCGS) Wheat Allergy Inflammatory Bowel Diseases (IBD) Type 1 Diabetes Autoimmune Liver Diseases Rheumatoid Arthritis Thyroid Disorders Genetic Conditions Casein/Cow's Milk Intolerance Non-Celiac Gluten Sensitivity (NCGS) Although it doesn't involve the autoimmune response seen in celiac disease, NCGS can lead to symptoms similar to those of celiac disease and may be associated with elevated tTG-IgA. NCGS is characterized by gluten-related symptoms without the autoimmune response and intestinal damage seen in celiac disease. The exact mechanisms leading to elevated tTG-IgA in NCGS are not fully understood, but it's believed that gluten sensitivity in NCGS may still induce an immune response, even though it differs from the autoimmune process seen in celiac disease. The presence of elevated tTG-IgA in NCGS underscores the complexity of gluten-related disorders and highlights the need for further research to elucidate the underlying immune responses and mechanisms associated with different gluten-related conditions. Wheat Allergy Individuals with a wheat allergy may produce antibodies, including tTG-IgA, as part of the allergic response. Individuals with a wheat allergy may also exhibit increased tTG-IgA levels. Wheat allergy is an immune-mediated response to proteins in wheat, distinct from the autoimmune nature of celiac disease. The presence of elevated tTG-IgA in individuals with a wheat allergy is somewhat perplexing, as tTG is an enzyme involved in the pathology of celiac disease, and its elevation is not commonly associated with allergies. One possible explanation is that the immune response triggered by a wheat allergy might lead to some cross-reactivity or shared epitopes with components involved in celiac disease, causing an increase in tTG-IgA. However, the exact mechanisms behind this phenomenon are not well-elucidated, and more research is needed to understand the connections between wheat allergy and the elevation of tTG-IgA. It emphasizes the intricate interplay between the immune system and various wheat-related disorders, requiring further exploration to unravel the complexities of immune responses in these conditions. Inflammatory Bowel Diseases (IBD) Conditions such as Crohn's disease and ulcerative colitis can cause gastrointestinal inflammation, and elevated tTG-IgA levels have been reported in some individuals with IBD. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) can also be observed in individuals with Inflammatory Bowel Diseases (IBD). IBD, which includes conditions like Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. The link between IBD and elevated tTG-IgA is not as straightforward as in celiac disease, and the reasons behind this elevation in some IBD patients remain a subject of research. One hypothesis suggests that the chronic inflammation and alterations in the intestinal mucosa associated with IBD may lead to increased permeability of the gut barrier. This heightened permeability might allow gluten proteins to interact with the immune system in a way that triggers the production of tTG-IgA. The intricate relationship between IBD and tTG-IgA elevation underscores the complex interplay between autoimmune responses and gastrointestinal disorders, requiring further investigation to uncover the underlying mechanisms and clinical implications. Type 1 Diabetes Some individuals with type 1 diabetes may have elevated tTG-IgA antibodies, and there is an increased risk of celiac disease in individuals with diabetes. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) can be found in individuals with Type 1 Diabetes (T1D), establishing a connection between these two autoimmune conditions. Both celiac disease and Type 1 Diabetes involve an autoimmune response, where the body's immune system mistakenly targets its own tissues. In the case of celiac disease, the immune system reacts to gluten, while in Type 1 Diabetes, it attacks the insulin-producing cells in the pancreas. The shared genetic susceptibility to autoimmune disorders could explain the co-occurrence of celiac disease and Type 1 Diabetes. The presence of certain genetic markers might predispose individuals to develop multiple autoimmune conditions. Additionally, environmental factors and common triggers in the immune response pathways could contribute to the simultaneous development of these disorders. Clinicians often monitor individuals with Type 1 Diabetes for celiac disease-related antibodies, including tTG-IgA, to identify and manage celiac disease early, highlighting the importance of understanding these interconnected autoimmune processes for comprehensive patient care. Thyroid Disorders Conditions such as autoimmune thyroiditis (Hashimoto's thyroiditis) and Graves' disease may be associated with elevated tTG-IgA antibodies. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) can be associated with thyroid disorders, particularly autoimmune thyroid conditions such as Hashimoto's thyroiditis. Hashimoto's thyroiditis is an autoimmune disease where the immune system attacks the thyroid gland, leading to inflammation and potential impairment of thyroid function. The link between celiac disease and autoimmune thyroid disorders has been observed, suggesting a shared genetic predisposition for autoimmune conditions. Individuals with celiac disease may have an increased risk of developing autoimmune thyroid disorders, and vice versa. The interconnected nature of autoimmune diseases suggests that the immune system's response to gluten in celiac disease might trigger or exacerbate autoimmune reactions in other organs, including the thyroid. Monitoring thyroid function and related antibodies, such as tTG-IgA, is crucial in individuals with celiac disease to identify and manage potential thyroid complications early. Understanding these complex interactions between autoimmune disorders is essential for comprehensive patient care and effective management of associated health conditions. Autoimmune Liver Diseases Certain autoimmune liver diseases, such as autoimmune hepatitis and primary biliary cirrhosis, may be associated with elevated tTG-IgA antibodies. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) may be detected in individuals with autoimmune liver diseases, particularly autoimmune hepatitis (AIH). Autoimmune hepatitis is a chronic inflammatory condition where the body's immune system erroneously attacks liver cells, leading to liver inflammation and potential damage. The connection between celiac disease and autoimmune liver diseases, although not fully understood, suggests shared autoimmune mechanisms. In some cases, individuals with celiac disease may experience immune system dysregulation that extends beyond the small intestine, leading to autoimmune reactions in other organs such as the liver. The presence of elevated tTG-IgA in individuals with autoimmune liver diseases underscores the complex interplay between various autoimmune conditions. Monitoring liver function and related antibodies is essential for comprehensive healthcare in individuals with celiac disease, as the autoimmune cascade can impact multiple organs. Understanding these connections aids in early detection, proper management, and improved overall outcomes for individuals with autoimmune liver diseases and concurrent celiac disease. Genetic Conditions Some genetic conditions, such as Down syndrome, may be associated with an increased prevalence of celiac disease and elevated tTG-IgA. Elevated tissue transglutaminase IgA antibodies (tTG-IgA) in individuals with genetic conditions such as Down syndrome can be attributed to the increased prevalence of autoimmune disorders in this population. Down syndrome, characterized by the presence of an extra copy of chromosome 21, is associated with a higher susceptibility to autoimmune conditions, including celiac disease. The genetic link between Down syndrome and celiac disease suggests a shared vulnerability to immune dysregulation. Individuals with Down syndrome may exhibit an elevated risk of developing autoimmune disorders due to alterations in immune system function associated with the genetic anomaly. The complex relationship between genetics and autoimmune responses underscores the importance of monitoring individuals with Down syndrome for various health conditions, including celiac disease. Early detection and management of celiac disease in individuals with Down syndrome are crucial for optimizing their overall health and well-being, considering the potential impact of untreated celiac disease on nutrient absorption and long-term health outcomes. Rheumatoid Arthritis Elevated tTG-IgA levels have been reported in some individuals with rheumatoid arthritis. The presence of elevated tissue transglutaminase IgA antibodies (tTG-IgA) in individuals with rheumatoid arthritis (RA) can be linked to the complex interplay between autoimmune disorders. Rheumatoid arthritis is a chronic inflammatory condition primarily affecting the joints, but it is increasingly recognized that individuals with RA may have an elevated risk of coexisting autoimmune diseases, including celiac disease. The shared genetic predisposition and immune dysregulation mechanisms contribute to the observed association between RA and elevated tTG-IgA. In the context of rheumatoid arthritis, the immune system mistakenly attacks the joints, leading to inflammation and joint damage. This dysregulated immune response may extend beyond the joints and manifest as an increased susceptibility to other autoimmune conditions, such as celiac disease. The identification of elevated tTG-IgA in individuals with RA underscores the importance of comprehensive health assessments in autoimmune disorders, as coexisting conditions may impact the overall management and prognosis of these individuals. Regular monitoring and collaboration between healthcare providers specializing in different autoimmune diseases are crucial for a holistic approach to patient care. Casein/Cow's Milk Intolerance Recent studies have shown that elevated tTG-IgA levels have been reported in some individuals with casein/cow's milk intolerance. Conclusion While it's true that elevated tissue transglutaminase IgA antibodies (tTG-IgA) can be associated with various conditions beyond celiac disease, including autoimmune disorders and genetic conditions, the tTG-IgA test remains a valuable tool in the diagnosis of celiac disease. In individuals with celiac disease, there is a specific immune response triggered by the ingestion of gluten, a protein found in wheat, barley, and rye. People with celiac disease often have higher levels of tTG-IgA in their blood due to the immune system's reaction to gluten. When gluten is ingested, individuals with celiac disease produce antibodies, including tTG-IgA, which target and attack the tissues of the small intestine. The elevated tTG-IgA levels are indicative of this immune response and the damage occurring in the intestinal lining. However, it's important to note that the interpretation of tTG-IgA levels should be done in the context of the individual's overall health, medical history, and the possibility of other conditions. A definitive diagnosis of celiac disease typically involves a combination of blood tests, genetic testing (HLA-DQ2 and HLA-DQ8), and, in some cases, an endoscopic biopsy of the small intestine. In summary, while elevated tTG-IgA levels are a common feature in celiac disease, the diagnosis involves a comprehensive assessment, and healthcare providers consider various factors to ensure accurate identification of the condition. It's crucial to interpret antibody test results in the context of the individual's clinical symptoms, medical history, and additional diagnostic tests. If tTG-IgA antibodies are elevated, further evaluation by a healthcare professional, typically including endoscopic procedures and biopsies, is often necessary to confirm or rule out celiac disease.

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 10/19/2020 - A team of researchers recently set out to determine the rates of functional abdominal pain disorders (FAPDs) and functional constipation in children with celiac disease on a strict gluten free diet. The research team included Fernanda Cristofori, MD; Mariaelena Tripaldi, MD; Giusi Lorusso, MD; Flavia Indrio, MD; Vincenzo Rutigliano, MD PhD; Domenico Piscitelli, MD; Stefania Castellaneta, MD; Vincenzo Bentivoglio, MD; and Ruggiero Francavilla, MD, PhD. They are variously affiliated with the Interdisciplinary Department of Medicine-Paediatric Section, University of Bari, Italy; the Department of Paediatrics San Paolo Hospital, Bari, Italy; Section of Pathology, Department of Emergency and Organ Transplantation, University of Bari, Italy; the San Giacomo Hospital, Monopoli (BA), Italy; the Faculty of Medicine, Paediatrics Specialization School University of Padua; and the “B. Trambusti” Department Giovanni XXIII Hospital- Via Amendola 207 Bari, Italy. For their prospective study, the team looked at 154 males and 263 women at a tertiary care center in Italy from 2016 through 2018. All patients were diagnosed with celiac disease according to ESPGHAN criteria, followed a strict gluten-free diet for more than 1 year, and also had negative results from serologic tests. Patients with celiac disease had higher rates of FAPDs, at 11.5%, compared to 6.7% for control subjects, while the relative risk was nearly 2%. Nearly 20% of celiac patients had functional constipation (functional constipation), and more than 7% had irritable bowel syndrome (IBS), defined by the Rome IV criteria, compared with more than 10% and 3.2% respectively for control subjects. Parents and children over 10 years old answered questions about pediatric gastrointestinal symptoms, according Rome IV criteria. As a control group, the team used 145 male and 227 female siblings or cousins, who had negative results from serologic test for celiac disease. People with celiac disease face an increased risk of both IBS and functional constipation. The team stresses the importance of strategies for managing IBS and functional constipation in celiac patients. Read more in CGHjournal.com