6-TISSUE TRANSGLUTAMINASE AUTOANTIBODIES AS PREDICTORS OF CELIAC DISEASE-last revised-06 (original) (raw)
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Indian Journal of Clinical Biochemistry, 2017
Traditionally small intestinal biopsy has been considered a gold standard for the diagnosis of celiac disease (CD). But now data has shown that serological markers like anti-tissue-transglutaminase antibodies (tTGA) can be used to make the diagnosis with great sensitivity and specificity. The objective of the present study was to evaluate whether patients with high probability of CD and high titre of tTGA, have a high probability of intestinal damage and may not require biopsy for final diagnosis. All the cases with tTGA levels C15 IU/ml and who subsequently underwent biopsy from July 2010 to June 2013 were selected. Histopathological findings graded as per Marsh classification were correlated with serum tTGA levels. Grade 3 lesions were considered diagnostic for the disease. Out of total 731 patients 470 had serum tTGA levels [100 IU/ml and 261 patients had \100 IU/ ml. Highest levels of tTGA (219.3 IU/ml) were seen in grade 3c which was [12 times the normal cutoff value. Mean serum tTGA in higher histological grade i.e. 3 (3a, 3b, 3c) was 186.7 IU/ml ([12 times the normal cut off value) as compared to grade 1 which was 108.9 IU/ml ([7 times the normal cut off value). Using a tTGA cutoff value of 70 IU/ml, sensitivity was found to be 83.9% while specificity was 56.10% with an overall accuracy of 77.7%. This study confirms that a small intestinal biopsy is not always necessary for the diagnosis of CD in symptomatic patients with high tTGA levels ([70 IU/ml).
Annals of Pathology and Laboratory Medicine, 2019
A definite diagnosis of Celiac disease is based on histological changes, including intraepithelial lymphocytosis, crypt hyperplasia, and varying degrees of villous atrophy, graded according to a classification system proposed by Marsh in 1992 and now widely used as modified Marsh grading depicted in table 1. [6-9] Duodenal biopsy remains the gold standard for diagnosis of CD, even though there are very specific serologic tests like anti-gluten and anti-tissue transglutaminase (anti-tTG) antibodies. Correlation of clinical, serologic, and histological features is essential for the definitive diagnosis of this condition. [10]
IgA Anti-Tissue Transglutaminase Antibodies, First Line in the Diagnosis of Celiac Disease
2011
According to the 2008 celiac disease working group run by Dr. A. Fassano under the auspices of the Federation of International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, celiac disease is a chronic immune-mediated enteropathy characterized by gluten sensitivity, which can affect any organ or system, having a wide range of clinical manifestations of variable severity. The serological diagnosis of celiac disease is based on high sensitivity and specificity tests. The measurement of IgA anti-tissue transglutaminase antibodies by ELISA is universally accepted in the screening of celiac disease. Using the gold standard represented by IgA anti-endomysium antibodies in a group of 890 children investigated during 2008-2009, we aimed to evaluate IgA anti-tissue transglutaminase antibodies (tTG IgA), as well as to establish their prevalence in associated diseases. Following the measurement of tTG IgA in the entire group, we obtained: sensitivity 773%, positive predictive value 55.2%, specificity 93.1%, negative predictive value 973%, p = 0.000, and in tTG IgA associations we obtained the value 0.51 for the ROC curve area. We found associations of tTG IgA with type 1 diabetes mellitus (235% prevalence), protein-calorie malnutrition (0.89% prevalence), and intestinal malabsorption (0.56% prevalence). Our results have a high specificity and sensitivity in the screening of celiac disease, while requiring a second method of confirmation.
Pediatric Gastroenterology, Hepatology & Nutrition
Purpose: This study aimed to evaluate a possible association between the anti-tissue transglutaminase antibody (anti-tTG) titer and stage of duodenal mucosal damage and assess a possible cutoff value of anti-tTG at which celiac disease (CD) may be diagnosed in children in conjunction with clinical judgment. Methods: This observational study was conducted at a gastroenterology clinic in a tertiary hospital from April 2012 to May 2013. Seventy children between 6-months and 18-years-old with suspected CD underwent celiac serology and duodenal biopsy. Statistical analyses were done using SPSS 16. Diagnostic test values were determined for comparing the anti-tTG titer with duodenal biopsy. An analysis of variance and Tukey-Kramer tests were performed for comparing the means between groups. A receiver operating characteristics curve was plotted to determine various cutoff values of anti-tTG. Results: The mean antibody titer increased with severity of Marsh staging (p<0.001). An immunoglobulin (Ig) A-tTG value at 115 AU/mL had 76% sensitivity and 100% specificity with a 100% positive predictive value (PPV) and 17% negative predictive value (NPV) for diagnosis of CD (p<0.001, 95% confidence interval [CI], 0.75-1). Conclusion: There is an association between the anti-tTG titer and stage of duodenal mucosal injury in children with CD. An anti-tTG value of 115 AU/mL (6.4 times the upper normal limit) had 76% sensitivity, 100% specificity, with a 100% PPV, and 17% NPV for diagnosing CD (95% CI, 0.75-1). This cutoff may be used in combination with clinical judgment to diagnose CD.
International journal of medical sciences, 2014
The prevalence of celiac disease (CD) among Japanese population has been unknown, whereas it has been increasingly recognized in the US and in the European countries. The aim of the present study is to identify possible cases with CD among Japanese population and clarify the relevance of screening for the disease. We conducted a serologic screening for the disease among 710 Japanese patients and 239 healthy volunteers at a local tertiary teaching hospital, using an anti-tissue transglutaminase IgA (TTG-IgA) test, and histological examination of the small intestines from the TTG-IgA positive subjects. There were no TTG-IgA positive sera among the healthy volunteers. Twenty of the patients (2.8%), including eight with malignant lymphoma, were tested positive for TTG-IgA. The histological examination of the eleven patients among those with positive TTG-IgA, seven showed villous atrophy and partial lymphocytes infiltration in the mucosa, which could be compatible to mucosal changes obse...
Anti-tTg-IgA is neither a Solved Problem nor a " closed case " in Celiac Disease Diagnosis
Anti-tissue transglutaminase (tTg) IgA are considered the most frequently used serological marker for celiac disease diagnosis. Despite its recommended leading position by the 2012 ESPGHAN diagnostic criteria, it exposes multiple false positive and negative titers. In view of the critical opinions expressed lately in the literature against the application of those criteria, the bias in the central place occupied by tTg-IgA in the new ESPGHAN CD Diagnostic Guidelines and the emergence of newer serological marker for celiac disease, it is hoped that the revised guidelines will open up the limited, problematic and single Tg2-IgA antibody for other or additional single or combined serological diagnostic markers.
IgA and IgG Antitransglutaminase 2 Antibodies in the Diagnosis of Celiac Disease
Screening for celiac disease (CD) dramatically improved when techniques able to measure blood autoantibodies against tissue transglutaminase 2 (TTG) were developed. Although typically increased in CD, these antibodies are not pathognomonic since they are also detected in several other autoimmune processes. IgA deficiency among celiac patients is more frequent than in general population (up to 25% vs 1-3%). This led to develop kits able to measure IgG-TTG, which until today represent a helpful diagnostic tool during diagnosis of CD in IgA deficient individuals. Today, commercial kits measuring IgG-TTG (and other) antibodies are widely available, are frequently used and create confusion in diagnosing CD in IgA-sufficient individuals. This is attributed to the fact that sensitivity and specificity of IgG-TTG is lower when applied to IgA-sufficient persons, and also because IgG-TTG is detected in several autoimmune disorders, with variable frequency and isotypes depending on the condition. Evidence analyzed indicate that to date available data: i) is insufficient to understand the difference of classes and subclasses detected in CD and other autoimmune conditions; ii) does not support the use of IgG-TTG for diagnosing CD in IgA-sufficient individuals and therefore iii) IgG should not be used in the routine diagnostic process of CD.
Nutrients
The diagnosis of celiac disease (CD) at the first diagnostic step requires the detection of specific class A antibodies to tissue transglutaminase type-2 (TG2 IgA) and the measurement of total immunoglobulin A (tIgA) to exclude IgA deficiency. The aim of the study was to evaluate the new quantitative immunoassay panel allowing for the detection of celiac-specific antibodies with the simultaneous determination of tIgA from the same sample of blood at one time. This retrospective study included 104 pediatric patients divided into groups with recognized CD and IgA deficiency (n = 20; 19%), immunocompetent children with CD (n = 28; 27%), children with IgA deficiency and without CD (n = 28; 27%), and the control group of immunocompetent children without CD (n = 28; 27%). Intestinal biopsy with histopathological evaluation (except five patients with CD who were diagnosed without biopsy) and measurement of reference celiac specific antibodies were performed in all children. Multiparametric...