scholarly journals Strongly Positive Tissue Transglutaminase Antibody Assays without Celiac Disease

2004 ◽  
Vol 18 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Hugh James Freeman

Celiac disease is a small bowel disorder characterized by flattened villi and crypt hyperplasia, often with malabsorption. Improvement occurs with a gluten-free diet. Sensitive and specific assays (eg, immunoglobulin A antibodies to tissue transglutaminase [tTG]) that can be quantified appear to be valuable tools for population screening studies. In addition, their use is expanding widely in the clinical practice arena, being employed as a method of case finding. In this evaluation, clinical use of a commercially available test kit was explored. Of 1330 samples submitted to our hospital laboratory by physicians in British Columbia, Alberta and the Yukon Territory (from 1999 to 2003, inclusive), 96 patients (7%) had increased values (normal range greater than 20 units) and markedly increased levels greater than 100 units were detected in 36 patients (3%). Of these, 14 patients (almost 40%) were referred to gastroenterologists in our hospital and all 14 had small intestinal biopsies. Of these, three patients (more than 20%) did not have celiac disease. Two had normal small bowel biopsies and one had unclassified sprue or 'sprue-like' intestinal disease that failed to respond to a gluten-free diet. The other 11 had biopsy-defined celiac disease. While the tTG assay may be a useful predictor of celiac disease, small intestinal biopsy is still required to confirm the diagnosis. In clinical practice, even strongly positive tTG results are not specific in individual patients, do not necessarily correlate with the degree of severity of biopsy change and, as a result, are also unlikely to be useful for monitoring diet compliance.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1665-1665
Author(s):  
R.K. Marwaha ◽  
Deepak Bansal ◽  
Amita Trehan ◽  
Akash Patel

Abstract Celiac disease (CD) is a malabsorptive disorder wherein the proximal small bowel mucosa is damaged as a result of dietary exposure to gluten. Children with intractable diarrhea and failure to thrive are diagnosed with relative ease. Diagnosis can however be challenging and is often delayed when children present with ‘difficult to treat anemia’, without overt gastrointestinal manifestations. The case records of 77 patients with CD were scrutinized retrospectively. Diagnosis was established with serology (tissue transglutaminase-IgA assay) in 46 (59.7%), serology along with small bowel mucosal biopsy in 23 (29.9%) and with biopsy alone in the remaining 8 (10.4%). All children belonged to the predominantly wheat consuming northern Indian states. The mean age at presentation was 99.1±34.8 months (median: 102, range: 22–168). Males outnumbered females in a ratio of 1.96:1. The mean duration of symptoms was 41±31.2 months (median: 36, range: 1–132). The overwhelming majority, i.e., 75 (97.4%) children had anemia (Hemoglobin <11 g/dL). Mean hemoglobin (Hb) was 7.0±2.2 g/dL (median: 7.2, range: 2.3–12.5). 52 (67.5%) had received iron supplements for sufficient lengths, without benefit. The red cell morphology was microcytic hypochromic in 37 (48%) and dimorphic in 33 (42.9%). A history of diarrhea was not forthcoming in 32 (41.6%) cases. 59 (76.6%) were malnourished, with a weight less than 80 % of expected for the age and 30 (39 %) were stunted, with a height falling below the 90% of expected. Two children had skin bleeds secondary to coagulopathy, due to Vitamin K malabsorption. In another 2, recurrent anemia was attributed to pulmonary hemosiderosis; further investigations for secondary causes unearthed CD. All children were initiated on an austere gluten free diet, along with iron and folic acid supplements for the initial 6–9 months. Mean duration of follow was 17.7±20.9 months. Improvement was perceptible within days of initiating gluten free diet. Of the 38 (49.4%) children who had a follow up of a year or longer, the mean Hb at the last visit had risen to 12.9±1.2 g/dL. Conclusions: Hematologists need to be aware of the mono-symptomatic presentation of CD with anemia. The typical period of presentation of CD is described to be between 6 mo and 2 yr of age. Prolonged duration of symptoms and a diagnosis at a relatively older age is striking in the index study. In a suggestive clinical background, identification of CD with serodiagnosis alone, without resorting to small bowel biopsy is increasingly gaining acceptance, as the specificity of newer serological assays is 95–98%. This is particularly true in tropical countries, where some degree of flattening of villi may be attributed to malnutrition and or infections, such as rotavirus enteritis, Giardia lamblia, or tropical sprue. A biopsy may be misleading in such cases. Heightened awareness is essential to identify CD at an early age, especially, in children in whom anemia is the dominant manifestation. The benefits of gluten free diet are apparent with the rise in hemoglobin and the improvement in growth parameters are gratifying both for physicians and the caretakers.


2008 ◽  
Vol 22 (3) ◽  
pp. 273-280 ◽  
Author(s):  
Hugh J Freeman

In adults with diarrhea or suspected malabsorption, a diagnosis of celiac disease requires that two criteria be fulfilled: first, a demonstration of typical pathological changes of untreated disease in biopsies from the proximal small bowel; and second, evidence should exist that clinical (and/or pathological) changes are gluten-dependent, most often as an unequivocal response to a gluten-free diet. Pathological abnormalities of celiac disease may include severe (‘flat’) or variably severe (mild or moderate) small bowel mucosal architectural abnormalities that are associated with both epithelial cell and lymphoid cell changes, including intraepithelial lymphocytosis. Architectural changes tend to be most severe in the duodenum and proximal jejunum and less severe, or absent, in the ileum. These findings, while characteristic of celiac disease, are not specific because several other conditions can produce similar changes. Some serological assays (eg, tissue transglutaminase antibody assays) are very useful screening tools in clinical practice because of their high specificity and sensitivity, but these do not provide a definitive diagnosis. The most critical step in the diagnosis of celiac disease is the demonstration of its gluten-dependent nature. The clinical response to gluten restriction in celiac disease is usually reflected in the resolution of diarrhea and weight gain. Normalization of biopsy changes can be first shown in the most distal intestinal sites of involvement, and later, sometimes only after prolonged periods (months to years) in the duodenum. Rarely, recurrent (or refractory) celiac disease may occur after an initial gluten-free diet response. Finally, some with ‘sprue-like intestinal disease’ cannot be classified because a diet response fails to occur. This may be a heterogeneous group, although some are eventually found to have a malignant lymphoma.


2017 ◽  
Vol 64 (1) ◽  
pp. 25-33
Author(s):  
Dan Olteanu ◽  
◽  
Alexandru Diaconescu ◽  
Radu Voiosu ◽  
Andrei Voiosu ◽  
...  

Coeliac disease incidence rised during the last 50 years and represents a concern by diagnostic problems and costs. The recent data regarding etiology, pathogeny, comparative diagnostic value of serology and small intestinal biopsy are summarised. The new data about refractory celiac disease to gluten free diet and therapeutic perspectives are also presented (glutenases, larazotide acetate, genetic alteration of cereals, tissulary transglutaminase inhibitors etc).


2015 ◽  
Vol 33 (2) ◽  
pp. 155-161 ◽  
Author(s):  
George J. Kahaly ◽  
Detlef Schuppan

Background: Celiac disease (CD) is a small-intestinal inflammatory disease that is triggered by the ingestion of the storage proteins (gluten) of wheat, barley and rye. Key Messages: Endocrine autoimmunity is prevalent in patients with CD and their relatives. The genes that predispose to endocrine autoimmune diseases, e.g. type 1 diabetes, autoimmune thyroid diseases, and Addison's disease, i.e. DR3-DQ2 and DR4-DQ8, are also the major genetic determinants of CD, which is the best understood HLA-linked disease. Thus, up to 30% of first-degree relatives both of patients with CD and/or endocrine autoimmunity are affected by the other disease. In CD, certain gluten proteins bind with high affinity to HLA-DQ2 or -DQ8 in the small-intestinal mucosa, to activate gluten-specific T cells which are instrumental in the destruction of the resorptive villi. Here, the autoantigen tissue transglutaminase increases the T cell response by generating deamidated gluten peptides that bind more strongly to DQ2 or DQ8. Classical symptoms such as diarrhea and consequences of malabsorption like anemia and osteoporosis are often absent in patients with (screening-detected) CD, but this absence does not significantly affect these patients' incidence of endocrine autoimmunity. Moreover, once autoimmunity is established, a gluten-free diet is not able to induce remission. However, ongoing studies attempt to address how far a gluten-free diet may prevent or retard the development of CD and endocrine autoimmunity in children at risk. Conclusions: The close relationship between CD and endocrine autoimmunity warrants a broader immune genetic and endocrine screening of CD patients and their relatives.


2016 ◽  
Vol 63 (4) ◽  
pp. 272-279
Author(s):  
Dan Olteanu ◽  
◽  
Alexandru Diaconescu ◽  
Radu Voiosu ◽  
Andrei Voiosu ◽  
...  

Coeliac disease incidence raised during the last 50 years and represents a concern by diagnostic problems and costs. The recent data regarding etiology, pathogeny, comparative diagnostic value of serology and small intestinal biopsy are summarised. New data about refractory celiac disease to gluten free diet and therapeutic perspectives are also presented (glutenases, larazotide acetate, genetic alteration of cereals, tissulary transglutaminase inhibitors etc).


2020 ◽  
Vol 8 (1) ◽  
pp. 48-53
Author(s):  
Ibrahim S. Alharbi ◽  
Abdul Monem Sweid ◽  
Muhammad Yousuf Memon ◽  
Saeed Alshieban ◽  
Ameirah Alanazi

AbstractBackground and objectivesAccording to recent guidelines, a diagnosis of celiac disease (CD) can be made without a biopsy, especially in children. There are no enough studies despite high prevalence and differences in genetic, race, and cultures. Therefore, we examined the correlation between tissue transglutaminase (TTG) and duodenal biopsy changes in our region because we are identical and different from others in culture, environment, and habits, and the correlation is same as that in different regions.MethodsA retrospective cohort study at the Ministry of National Guard Health Affaires (NGHA) health care facilities that are distributed throughout kingdom of Saudi Arabia from April 19, 2015, till March 29, 2018. This study used the BESTCARE system that includes data from all NGHA facilities; data from 513 patients with CD were collected. All patients diagnosed with celiac disease aged 15 years or more, confirmed by improvement on gluten-free diet (GFD), and were not on GFD before endoscopy or serology test or both of them were included in the study, and the TTG IgA level was measured at the same time or within 2–3 months of biopsy date. The exclusion criteria were negative duodenal biopsy, which is less than 2; patients with negative biopsy and negative serology; patients who were on GFD before testing, and any patients known to have immunity diseases or illness causing mucosal changes. The TTG IgA level was measured in IU/ mL and was labeled as negative (<20 IU/mL) and positive (≥ 20 IU/mL) based on the cutoff value. However, Intestinal biopsy findings were identified as Marsh classification groups.ResultsOne hundred thirty-four patients who met the inclusion criteria were included in the study. Median age of our sample was 24 years (16–37 years). Among these, 99 (73.88%) were female patients, whereas male patients were only 35 (26.12%). Histopathologic investigation of intestinal biopsy were Marsh 0 group was 16 cases (11.9%), Marsh 1 group was 8 cases (6%), Marsh 2 group was 4 cases (3%), Marsh 3a group was 32 cases (23.9%), Marsh 3b group was 64 cases (47.8%), and Marsh 3c group was 10 cases (7.5%). The TTG IgA antibody serology groups were <20 IU/mL in 13 cases (9.7%) and ≥20 IU/mL in 121 cases (90.3%). Among all patients with CD who had negative biopsy (Marsh 0 group), 16 (100%) of them had positive TTG IgA antibody. However, among patients with Marsh 1 group biopsy, 5 (62.5%) cases had negative TTG IgA antibody compared with 3 (37.5%) positive cases. Of the four cases (100%) with Marsh 2 group, all of them had positive TTG IgA antibody. However, in Marsh 3a group biopsy, 3 (9.4%) cases had negative TTG IgA antibody compared with 29 (90.6%) cases with positive TTG IgA antibody. Furthermore, among the patients with Marsh 3b group biopsy, 5 (7.8%) had negative antibody and 59 (92.2%) had positive serology. Of all biopsies of Marsh 3c group, 10 (100 %) had positive TTG IgA antibody.ConclusionsIn perspective of high prevalence of CD in KSA, even more than western countries, we can pretend that positive TTG antibody tests can be applied for the diagnosis of CD without biopsy, particularly in symptomatic patients along with high titer, that is, 5–10 times the upper limit of normal (ULN). However, to validate it further, we need larger prospective studies in which duodenal biopsies should be taken according to recommended protocol and should be interpreted by experienced pathologist. Furthermore, biopsy is still needed in patients who do not show clinical improvement on a gluten-free diet and in cases with mildly or moderately elevated TTG IgA.


2018 ◽  
Author(s):  
Ciarán P Kelly ◽  
Satya Kurada ◽  
Mariana Urquiaga

Celiac disease (CD) is an autoimmune disorder characterized by an immune response to gluten peptides in wheat, barley, and rye. The diagnosis of celiac disease is confirmed by three important characteristics: consistent symptoms, positive celiac-specific serology, and small intestinal biopsy findings of inflammation, crypt hyperplasia, and villous atrophy. CD may present with overt gastrointestinal symptoms, including diarrhea (or constipation), weight loss, and abdominal bloating and discomfort, or covertly with micronutrient deficiencies such as iron deficiency with anemia. A gluten-free diet (GFD) remains the mainstay of treatment. The aim of this review is to highlight the pathogenesis of CD, concepts and challenges associated with a GFD, and nutritional management of CD applicable in clinical practice to internists, gastroenterologists, and dietitians. Patients should be referred to an expert celiac dietitian for education on adherence to a GFD to address gluten contamination in the diet, the psychosocial implications of following a GFD, and macro- and micronutrient disequilibria arising from celiac disease and the GFD. Several novel therapeutics are on the horizon in various stages of development, including glutenases, antigliadin antibodies, tight junction regulators, modulation of the immune response to gliadin, and efforts to engineer less toxic gluten-containing foodstuffs. This review contains 3 figures, 5 tables, and 61 references. Key words: celiac disease, genetic engineering, food engineering, gluten, glutenases, gluten-free diet, oats, IgY, nutrition, tight junction regulators, wheat


2017 ◽  
Author(s):  
Ciarán P Kelly ◽  
Satya Kurada ◽  
Mariana Urquiaga

Celiac disease (CD) is an autoimmune disorder characterized by an immune response to gluten peptides in wheat, barley, and rye. The diagnosis of celiac disease is confirmed by three important characteristics: consistent symptoms, positive celiac-specific serology, and small intestinal biopsy findings of inflammation, crypt hyperplasia, and villous atrophy. CD may present with overt gastrointestinal symptoms, including diarrhea (or constipation), weight loss, and abdominal bloating and discomfort, or covertly with micronutrient deficiencies such as iron deficiency with anemia. A gluten-free diet (GFD) remains the mainstay of treatment. The aim of this review is to highlight the pathogenesis of CD, concepts and challenges associated with a GFD, and nutritional management of CD applicable in clinical practice to internists, gastroenterologists, and dietitians. Patients should be referred to an expert celiac dietitian for education on adherence to a GFD to address gluten contamination in the diet, the psychosocial implications of following a GFD, and macro- and micronutrient disequilibria arising from celiac disease and the GFD. Several novel therapeutics are on the horizon in various stages of development, including glutenases, antigliadin antibodies, tight junction regulators, modulation of the immune response to gliadin, and efforts to engineer less toxic gluten-containing foodstuffs. This review contains 3 figures, 5 tables, and 61 references. Key words: celiac disease, genetic engineering, food engineering, gluten, glutenases, gluten-free diet, oats, IgY, nutrition, tight junction regulators, wheat


2019 ◽  
Vol 35 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Grant L. Hom ◽  
Brian L. Hom ◽  
Barbara Kaplan ◽  
A. David Rothner

Background: Few studies exist examining the frequency of primary headache in children with celiac disease and the impact of a gluten-free diet on primary headache symptomology. This study explores characteristics and frequency of headaches in children with celiac disease and response to gluten-free diet at a single institution. Methods: Medical records were reviewed for children with celiac disease confirmed by the presence of elevated tissue transglutaminase IgA levels and histologic changes consistent with the diagnosis of celiac disease on small bowel biopsy. Eligible participants were contacted via letter for participation in a phone survey regarding headaches. Phone interviews were conducted 2 weeks after notification and lasted approximately 10 minutes. Headaches were classified according to ICHD-3 criteria. Results: 247 eligible patients or their families were contacted. A total of 132 (53.44%) agreed to participate. One participant was excluded due to insufficient information provided. Overall, 51 of 131 participants had recurrent headache defined as at least 1 episode per month (39%, 95% confidence interval [CI]: 31%-47%) and 33 had migraine with or without aura (25%, 95% CI: 18%-33%). Twenty-eight had frequent tension-type headache (22%, 95% CI: 15%-29%). Thirty-two participants noted headaches before a confirmed diagnosis of celiac disease. Twenty-two of 32 participants (68.75%) noticed decreased headache frequency or intensity, or both, after starting the gluten-free diet. Conclusion: This study suggests that at least one-third of children and adolescents with celiac disease have recurrent headaches at the time of diagnosis. A gluten-free diet led to improved headache symptomology in a significant number of these patients.


2014 ◽  
Vol 146 (5) ◽  
pp. S-349
Author(s):  
Sudarshan A. Shetty ◽  
Dhiraj P. Dhotre ◽  
Khushboo Bhatia ◽  
Anil K. Verma ◽  
Asha Mishra ◽  
...  

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