IgG Antibodies against Deamidated Gliadin Peptides for Diagnosis of Celiac Disease in Patients with IgA Deficiency (original) (raw)
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Clinica Chimica Acta, 2010
Background: Detection of IgG antibodies against deamidated gliadin peptides (DGP) is more sensitive and more specific for celiac disease than detection of IgG antibodies against native gliadin. Our aim was to evaluate the technical performance and diagnostic accuracy of four commercial IgG anti-DGP assays. Methods: Commercial IgG anti-DGP assays from Euroimmun, Inova, Phadia and The Binding Site were evaluated and their diagnostic accuracy (sensitivity and specificity) compared to other serologic assays for celiac disease (3 IgA and 2 IgG anti-tTG assays, 1 IgA and 1 IgG anti-gliadin assay, 1 IgA anti-DGP assay). The study population consisted of 86 consecutive CD patients and 741 disease controls. Results: The technical performance (linearity, interference and imprecision) of the IgG anti-DGP assays was acceptable. The sensitivity of the IgG anti-DGP assays varied between 76.7% and 86.0% at the cut-off recommended by the manufacturer and between 74.4% and 86.0% at the cut-off that corresponded to a specificity of 98%. The specificity varied between 97.3% and 99.3%. The diagnostic accuracy of the IgG anti-DGP assays was comparable to the diagnostic accuracy of the IgA anti-tTG assays. The sensitivity of the IgG anti-DGP assays was significantly better than sensitivity of the IgG anti-tTG assays (p b 0.05) and the specificity was significantly better than the IgA and IgG anti-gliadin assays (p b 0.05). Conclusions: The overall performance of the four IgG anti-DGP assays was acceptable and the diagnostic accuracy comparable to the three IgA anti-tTG assays.
Clinical and Vaccine Immunology, 2005
The role of immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (IgA-tTG) as predictors of untreated celiac disease (CoD) is well documented, and the presence and levels of these antibodies are most accurately monitored with native or recombinant human antigens. However, IgA-deficient CoD patients are not identified by IgA serology, and conflicting results concerning the diagnostic validity of IgG antibodies against gliadin (IgG-AGA), endomysium (IgG-EmA), and tTG (IgG-tTG) have been reported. The aim of the present study was to evaluate the utility of IgG-tTG for the detection of CoD in IgA-deficient patients. Samples from 115 IgA-deficient and 200 IgA-sufficient subjects were collected and tested for the presence of IgA and IgG antibodies against tTG, EmA, and AGA. Antibodies against tTG were measured by an enzyme-linked immunosorbent assay based on recombinant human tTG, and antibodies against EmA were determined by immunofluorescence. The values for IgG-tTG showed a higher correlation (correlation coefficient [r] ؍ 0.91) with those for IgG-EmA for the IgA-deficient subjects than for the IgA-sufficient subjects (r ؍ 0.88). The overall concordance of the positive and negative results between IgG-tTG and IgG-EmA was 97%, and the IgG-tTG assay discriminated between IgG-EmA-positive and -negative subjects with IgA deficiency at a rate of 100%. Elevated levels of IgG-tTG and IgG-EmA were measured in 70% of the IgA-sufficient subjects. IgG-tTG detection with recombinant human tTG is a good alternative to IgG-EmA detection, and the addition of IgG-tTG assessment to present screening methods may improve the ability to identify IgA-deficient subjects with CoD.
Archivos Argentinos De Pediatria, 2019
Objective. To compare the performance of IgA anti-tissue transglutaminase antibodies (IgA anti-tTG), IgA anti-endomysial antibodies (IgA EMA), and IgA/IgG antibodies against deamidated gliadin peptides (IgA/IgG anti-DGP) for the diagnosis of celiac disease. Methods. Descriptive study in patients with celiac disease. Anti-DGP (IgA/IgG), IgA EMA, IgA anti-tTG antibodies were measured and an intestinal biopsy was done. Sex: female (61 %). Median age: 78.4 months old. Results. A total of 136 children were included; 108 had high IgA anti-DGP titers; 124, increased IgG anti-DGP titers; 128, positive IgA EMA titers; and 130, increased IgA anti-tTG titers. High IgG anti-DGP titers were observed in 4/6 patients with negative IgA anti-tTG antibodies. The combination of IgG anti-DGP + IgA anti-tTG antibodies showed a positive correlation in 134 patients and the IgG anti-DGP + EMA combination was positive in 133 children. Conclusion. IgA EMA, IgA anti-tTG, and IgG anti-DGP antibodies exhibited an adequate specificity and sensitivity. The IgG anti-DGP/anti-tTG combination showed a 98-99 % sensitivity and a 100 % specificity. The anti-tTG and IgG anti-DGP option yields excellent results, with a low cost and independence from the observer.
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.
Clinica Chimica Acta, 2010
Background: We investigated whether taking into account IgA anti-tissue transglutaminase antibody concentration (IgA anti-tTG) and total IgA concentration could improve clinical interpretation of serologic testing for celiac disease (CD). Methods: We retrospectively identified 43 consecutive newly diagnosed CD patients and 545 consecutive disease control patients who had an IgA anti-tTG request during the 42-month study period and for whom intestinal biopsy results were available. Results: Sensitivity and specificity of the IgA anti-tTG assay from Genesis was 95.3% and 92.7%, respectively, with a likelihood ratio (LR) of 12.4. The LR for CD markedly increased with increasing IgA anti-tTG concentration (from 2.0 for results between 7 and 20 U/ml up to 319 for results > 100 U/ml). The LR for CD was also higher in patients with a normal IgA concentration (0.82-4.53 g/L) compared to patients with an increased IgA concentration (15.3 vs. 3.1, respectively). These observations were confirmed with a second IgA anti-tTG assay from BioRad. Conclusion: Sensitivity of IgA anti-tTG was good. Specificity, however, was reduced when IgA anti-tTG was weak positive or when the IgA concentration was increased. Taking into account IgA anti-tTG concentration and IgA concentration improves clinical interpretation of serologic testing for CD.
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.
Clinical …, 2007
Background: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. Methods: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). Results: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964 -0.998) for IgA a-DGP, 0.989 (0.954 -0.999) for IgG a-DGP, 0.996 (0.966 -0.998) for blended conjugated of IgA ؉ IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA ؉ IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff.
Clinical Chemistry, 2007
Background: Noninvasive serologic tests have shown high diagnostic accuracy for celiac disease (CD) in selected populations. Our aim was to determine prospectively the performance of CD-related serology in individuals undergoing intestinal biopsy because of clinical suspicion of small-bowel disorders. Methods: We enrolled 141 unselected consecutive adult patients attending a small-bowel disease clinic. Patients underwent endoscopy and biopsy; serum samples were obtained at that time for measurements of anti-tissue transglutaminase (a-tTG), IgA and IgG anti-deamidated gliadin-related peptide (a-DGP), and IgA antiactin antibodies (AAAs). Characterization of patients was based on histological criteria (Marsh type II lesion or greater). Results: The prevalence of CD was 42.5%. Sensitivity, specificity, and positive and negative predictive values were >90% for most assays. Diagnostic accuracy based on ROC curve analysis was similar for all assays [area under the curve (95% CI): 0.996 (0.967-0.998) for a-tTG, 0.995 (0.964 -0.998) for IgA a-DGP, 0.989 (0.954 -0.999) for IgG a-DGP, 0.996 (0.966 -0.998) for blended conjugated of IgA ؉ IgG a-DGP in a single assay, and 0.967 (0.922-0.990) for AAA]. The combinations of 2 tests, IgG a-DGP plus IgA a-tTG or the single blended conjugate detecting IgA ؉ IgG a-DGP plus IgA a-tTG had 100% positive and negative predictive values if concentrations of both tests in either combination were above or below the cutoff.
Serological assessment for celiac disease in IgA deficient adults
PloS one, 2014
Selective immunoglobulin A deficiency is the most common primary immunodeficiency disorder that is strongly overrepresented among patients with celiac disease (CD). IgG antibodies against tissue transglutaminase (tTG) and deamidated gliadin peptides (DGP) serve as serological markers for CD in IgA deficient individuals, although the diagnostic value remains uncertain. The aim of this study was to investigate the prevalence of these markers in a large cohort of IgA deficient adults with confirmed or suspected CD and relate the findings to gluten free diet. Sera from 488,156 individuals were screened for CD in seven Swedish clinical immunology laboratories between 1998 and 2012. In total, 356 out of 1,414 identified IgA deficient adults agreed to participate in this study and were resampled. Forty-seven IgA deficient blood donors served as controls. Analyses of IgG antibodies against tTG and DGP as well as HLA typing were performed and a questionnaire was used to investigate adherence...
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...