Celiac Disease and Endocrine Autoimmunity

2015 ◽  
Vol 33 (2) ◽  
pp. 155-161 ◽  
Author(s):  
George J. Kahaly ◽  
Detlef Schuppan
Keyword(s):  
Celiac Disease ◽  
Storage Proteins ◽  
Tissue Transglutaminase ◽  
T Cell Response ◽  
Gluten Free Diet ◽  
Small Intestinal Mucosa ◽  
Gluten Free ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid ◽  
Small Intestinal

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.

scholarly journals Strongly Positive Tissue Transglutaminase Antibody Assays without Celiac Disease

2004 ◽  
Vol 18 (1) ◽  
pp. 25-28 ◽  
Author(s):  
Hugh James Freeman
Keyword(s):  
Celiac Disease ◽  
Clinical Practice ◽  
Small Bowel ◽  
Tissue Transglutaminase ◽  
Yukon Territory ◽  
Gluten Free Diet ◽  
Intestinal Biopsy ◽  
Gluten Free ◽  
Test Kit ◽  
Small Intestinal

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.

scholarly journals The Challenge of Treatment in Potential Celiac Disease

2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Chiara Maria Trovato ◽  
Monica Montuori ◽  
Francesco Valitutti ◽  
Beatrice Leter ◽  
Salvatore Cucchiara ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Immunoglobulin A ◽  
Intraepithelial Lymphocytes ◽  
Gluten Free Diet ◽  
Small Intestinal Mucosa ◽  
Gluten Free ◽  
Main Challenge ◽  
Genetic Features ◽  
Diagnostic Work ◽  
Work Up

Potential celiac disease (PCD) is defined by the presence of positive serum antibodies, HLA-DQ2/DQ8 haplotypes, and a normal small intestinal mucosa (Marsh grade 0-1). This condition occurs in one-fifth of celiac disease (CD) patients and usually represents a clinical challenge. We reviewed genetic, histologic, and clinical features of this specific condition by performing a systematic search on MEDLINE, Embase, and Scholar database. Accordingly, we identified different genetic features in patients with PCD compared to the classical forms. Frequently, signs of inflammation (deposits of immunoglobulin A (IgA) and/or increased number of intraepithelial lymphocytes) can be clearly identify in the mucosa of PCD patients after an accurate histological assessment. Finally, the main challenge is represented by the treatment: the gluten-free diet should be considered only in the presence of gluten-dependent symptoms in both children and adults. What is known: (i) potential celiac disease (PCD) occurs in one-fifth of all celiac diseases (CD), and (ii) despite the absence of classical lesions, clear signs of inflammation are often detectable. What is new: (i) patients with PCD show different genetic features, and (ii) the presence of gluten-dependent symptoms is the main determinant to initiate the gluten-free diet, after a complete diagnostic work-up.

A Single Institution’s Experience of Primary Headache in Children With Celiac Disease

2019 ◽  
Vol 35 (1) ◽  
pp. 37-41 ◽  
Author(s):  
Grant L. Hom ◽  
Brian L. Hom ◽  
Barbara Kaplan ◽  
A. David Rothner
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Primary Headache ◽  
Tension Type Headache ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Phone Survey ◽  
Type Headache ◽  
The Impact ◽  
Histologic Changes

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.

scholarly journals Sa1993 Constitutional and Functional Small Intestinal Microbiome of Patients With Celiac Disease, First Degree Relatives and Effect of Gluten Free Diet on Them

2014 ◽  
Vol 146 (5) ◽  
pp. S-349
Author(s):  
Sudarshan A. Shetty ◽  
Dhiraj P. Dhotre ◽  
Khushboo Bhatia ◽  
Anil K. Verma ◽  
Asha Mishra ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Gluten Free Diet ◽  
Intestinal Microbiome ◽  
Gluten Free ◽  
First Degree Relatives ◽  
Small Intestinal

scholarly journals Slow Decrease of Anti-Tissue Transglutaminase Antibody Positivity In Children With Celiac Disease After Starting the Gluten-Free Diet

2020 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Chiara Monachesi ◽  
Anil K. Verma ◽  
Giulia Naspi Catassi ◽  
Simona Gatti ◽  
Elena Lionetti ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Slow Decrease ◽  
Antibody Positivity

Serodiagnosis of Celiac Disease in Children Referred for Evaluation of Anemia: A Pediatric Hematology Unit’s Experience.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1665-1665
Author(s):  
R.K. Marwaha ◽  
Deepak Bansal ◽  
Amita Trehan ◽  
Akash Patel
Keyword(s):  
Celiac Disease ◽  
Small Bowel ◽  
Tissue Transglutaminase ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Indian States ◽  
Duration Of Symptoms ◽  
Pulmonary Hemosiderosis ◽  
Proximal Small Bowel ◽  
The Mean

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.

An Attempt of Specific Desensitising Treatment with Gliadin in Celiac Disease

2005 ◽  
Vol 18 (4) ◽  
pp. 709-714 ◽  
Author(s):  
G. Patriarca ◽  
N. Pogna ◽  
G. Cammarota ◽  
D. Schiavino ◽  
C. Lombardo ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Clinical Manifestations ◽  
Current Treatment ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Dietary Regimen ◽  
New Approach ◽  
Tissue Transglutaminase Antibodies

Gluten-free diet is the current treatment of celiac disease. We decided to verify the occurrence of histological and serological modification and/or clinical manifestations during a gradual and progressive introduction of gliadin in the diet and if it may induce a tolerance to food, as it occurs in allergic patients. We studied the case of a celiac woman with complete clinical and histological remittance after 10 years of gluten free diet. She took increasing daily doses of gliadin, reaching the final dose of 9 g of gliadin (15 g of gluten) in 6 months. Then she started a free dietary regimen. During the 15-month follow-up period esophago-gastro-duodenoscopy showed normal Kerckring folds and villi. Anti-gliadin, anti-endomysium and anti-tissue-transglutaminase antibodies, as well as the haematological and biochemical parameters remained normal. Our results represent a new approach in the research concerning celiac disease, and could provide a future line of study for its management.

scholarly journals Non-Invasive Biomarkers for Celiac Disease

2019 ◽  
Vol 8 (6) ◽  
pp. 885 ◽  
Author(s):  
Alka Singh ◽  
Atreyi Pramanik ◽  
Pragyan Acharya ◽  
Govind K. Makharia
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
High Titer ◽  
Invasive Procedure ◽  
Gluten Free Diet ◽  
New Drugs ◽  
Current Status ◽  
Common Disease ◽  
Gluten Free ◽  
Strict Adherence

Once thought to be uncommon, celiac disease has now become a common disease globally. While avoidance of the gluten-containing diet is the only effective treatment so far, many new targets are being explored for the development of new drugs for its treatment. The endpoints of therapy include not only reversal of symptoms, normalization of immunological abnormalities and healing of mucosa, but also maintenance of remission of the disease by strict adherence of the gluten-free diet (GFD). There is no single gold standard test for the diagnosis of celiac disease and the diagnosis is based on the presence of a combination of characteristics including the presence of a celiac-specific antibody (anti-tissue transglutaminase antibody, anti-endomysial antibody or anti-deamidated gliadin peptide antibody) and demonstration of villous abnormalities. While the demonstration of enteropathy is an important criterion for a definite diagnosis of celiac disease, it requires endoscopic examination which is perceived as an invasive procedure. The capability of prediction of enteropathy by the presence of the high titer of anti-tissue transglutaminase antibody led to an option of making a diagnosis even without obtaining mucosal biopsies. While present day diagnostic tests are great, they, however, have certain limitations. Therefore, there is a need for biomarkers for screening of patients, prediction of enteropathy, and monitoring of patients for adherence of the gluten-free diet. Efforts are now being made to explore various biomarkers which reflect different changes that occur in the intestinal mucosa using modern day tools including transcriptomics, proteomics, and metabolomics. In the present review, we have discussed comprehensively the pros and cons of available biomarkers and also summarized the current status of emerging biomarkers for the screening, diagnosis, and monitoring of celiac disease.

scholarly journals New Perspectives on Gluten-Free Diet

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3540
Author(s):  
Paolo Usai-Satta ◽  
Mariantonia Lai
Keyword(s):  
Celiac Disease ◽  
Intestinal Inflammation ◽  
Gluten Free Diet ◽  
Gluten Free ◽  
Small Intestinal

Celiac disease (CD) is a permanent, chronic, gluten-sensitive disorder characterized by small intestinal inflammation and malabsorption in genetically predisposed individuals [...]

Detoxification of Gluten by Means of Enzymatic Treatment

2012 ◽  
Vol 95 (2) ◽  
pp. 356-363 ◽  
Author(s):  
Herbert Wieser ◽  
Peter Koehler
Keyword(s):  
Small Intestine ◽  
Storage Proteins ◽  
Raw Materials ◽  
Specific Antigen ◽  
Gluten Free Diet ◽  
Small Intestinal Mucosa ◽  
Gluten Free ◽  
Gluten Peptides ◽  
Isopeptide Bonds ◽  
Gastrointestinal Enzymes

Abstract Celiac disease (CD) is an inflammatory disease of the upper small intestine in genetically predisposed individuals caused by glutamine- and proline-rich peptides from cereal storage proteins (gluten) with a minimal length of nine amino acids. Such peptides are insufficiently degraded by gastrointestinal enzymes; they permeate the lymphatic tissue, are bound to celiac-specific, antigen-presenting cells, and stimulate intestinal T-cells. The typical clinical pattern is a flat small intestinal mucosa and malabsorption. Currently, the only therapy is a strict, lifelong gluten-free diet. Recent research has shown that gluten and gluten peptides can be degraded by prolyl endopeptidases from different sources. These peptidases can either be used to produce gluten-free foods from gluten-containing raw materials, or they have been suggested as an oral therapy for CD, in which dietary gluten is hydrolyzed by coingested peptidases already in the stomach, thus preventing CD-specific immune reactions in the small intestine. This would be an alternative for CD patients to the gluten-free diet. Furthermore, microbial transglutaminase could be used to detoxify gluten either by selectively modifying glutamine residues of intact gluten by transamidation with lysine methyl ester or by crosslinking gluten peptides in beverages via isopeptide bonds so that they can be removed by filtration.

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