scholarly journals IgG Antibodies against Deamidated Gliadin Peptides for Diagnosis of Celiac Disease in Patients with IgA Deficiency

2010 ◽  
Vol 56 (3) ◽  
pp. 464-468 ◽  
Author(s):  
Danilo Villalta ◽  
Elio Tonutti ◽  
Christian Prause ◽  
Sibylle Koletzko ◽  
H Holm Uhlig ◽  
...  

AbstractBackground: Assays for IgG antibodies against deamidated gliadin (IgG-anti-dGli) are comparable in performance with tests detecting IgA antibodies against tissue transglutaminase (IgA-anti-tTG) in diagnosing celiac disease (CD). IgA-anti-tTG are absent in IgA deficiency, a condition often associated with CD. In IgA deficiency, IgG-anti-tTG, which have a lower overall diagnostic accuracy, are routinely measured. We examined whether IgG-anti-dGli would be useful for diagnosing CD in patients with IgA deficiency.Methods: We studied 34 IgA-deficient CD patients, 185 IgA-competent newly diagnosed children with CD, 316 children without CD, 400 adult blood donors, and 6 control IgA-deficient individuals without CD. Anti-dGli and anti-tTG were measured by ELISA, and endomysium antibodies (EmA) were measured by immunofluorescence on monkey esophagus (IgA as well as IgG class for all antibodies). We calculated diagnostic sensitivity (percentage of patients above cutoff with 95% CIs) according to age-specific cutoffs for 95% diagnostic specificity and according to cutoffs proposed by the manufacturer of the assays.Results: No IgA-deficient CD patients were positive for any IgA-based antibody assay. Diagnostic sensitivity of IgG-anti-tTG was 91.2% (95% CI 76.3%–97.7%) according to age-specific cutoffs and 82.4% (66.1%–92.0%) according to manufacturer cutoffs. The diagnostic sensitivity of IgG-EmA was 75.8% (58.8%–87.4%) and the sensitivity of IgG-anti-dGli was 88.2% (72.8%–95.9%) according to both cutoffs.Conclusions: IgG-anti-dGli and IgG-anti-tTG have comparable diagnostic sensitivities for IgA-deficient celiac patients. IgG-anti-dGli may be useful for diagnosing CD in IgA-deficient patients.

2005 ◽  
Vol 12 (2) ◽  
pp. 254-258 ◽  
Author(s):  
Ingrid Dahlbom ◽  
Martin Olsson ◽  
Nahal Kazemi Forooz ◽  
Anders G. Sjöholm ◽  
Lennart Truedsson ◽  
...  

ABSTRACT 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.


2004 ◽  
Vol 50 (11) ◽  
pp. 2125-2135 ◽  
Author(s):  
Britta Van Meensel ◽  
Martin Hiele ◽  
Ilse Hoffman ◽  
Severine Vermeire ◽  
Paul Rutgeerts ◽  
...  

Abstract Background: Anti-tissue transglutaminase (tTG) assays that use human tTG as antigen have recently become available. We evaluated commercially available assays with human tTG antigen to estimate their diagnostic accuracies and to determine whether they agree sufficiently to be used interchangeably. Methods: Ten commercially available second-generation anti-tTG assays were evaluated. The following populations were studied: celiac disease (CD) patients at the time of diagnosis without (n = 70) or with (n = 5) IgA deficiency; diseased controls (n = 70); and CD patients without (n = 28) or with (n = 2) IgA deficiency during follow-up. All individuals included in the study underwent intestinal biopsy. Technical performance (linearity, interference, precision, correlation, and agreement) and diagnostic accuracy (sensitivity and specificity) were compared. Anti-gliadin and anti-endomysium antibodies were also measured. Results: IgA anti-tTG results correlated well overall, but numerical values differed. Diagnostic sensitivity ranged between 91% and 97% and specificity between 96% and 100%. These were higher than the sensitivity and specificity of the IgA endomysium assay and the IgA gliadin assay. Generally, IgG anti-tTG was less sensitive but more specific than IgG anti-gliadin for the diagnosis of CD in the small group of IgA-deficient patients. Conclusions: Overall diagnostic performance of IgA tTG assays is acceptable and comparable among the different assays, but numerical values differ. Standardization is needed.


2002 ◽  
Vol 9 (6) ◽  
pp. 1295-1300 ◽  
Author(s):  
V. Kumar ◽  
M. Jarzabek-Chorzelska ◽  
J. Sulej ◽  
Krystyna Karnewska ◽  
T. Farrell ◽  
...  

ABSTRACT Immunoglobulin A (IgA) deficiency is 10 to 15 times more common in patients with celiac disease (CD) than in healthy subjects. Serological tests have become the preferred methods of diagnosing CD in both symptomatic and asymptomatic patients. However, commercially available serological methods are limited in that they detect only the IgA isotype of antibodies (with the exception of IgG gliadin assays); hence, IgA-deficient patients with CD may yield false-negative serology. Fifteen pediatric patients with CD and 10 IgA-deficient pediatric patients without CD were examined for IgA and IgG antibodies to endomysium, gliadin, and tissue transglutaminase. Twenty-five specimens from patients with IgA deficiency were examined. Fifteen were from patients with CD, and 10 were patients without CD. All 15 IgA-deficient patients with CD were positive for endomysium antibodies of the IgG isotype and for IgG gliadin antibodies. All but one of the IgA-deficient patients with CD were also positive for IgG tissue transglutaminase antibodies. None of the IgA-deficient patients without CD were positive for any of the antibody markers. All the specimens examined were also negative for IgA-specific antibodies to endomysium, gliadin, and tissue transglutaminase. IgG-specific antibody tests for endomysium, gliadin, and tissue transglutaminase are useful for the identification of IgA-deficient patients with CD. IgG antibody tests along with tests routinely being used in clinical laboratories can reliably detect all active patients with CD. In addition, the levels of these CD-specific IgG antibodies could be used to monitor patient dietary compliance.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ider Oujamaa ◽  
Majda Sebbani ◽  
Lahcen Elmoumou ◽  
Aïcha Bourrahouate ◽  
Rabiy El Qadiry ◽  
...  

Objective. We aimed to determine the prevalence of specific auto-antibodies to celiac disease (CD) in Moroccan type 1 diabetic (T1D) patients and compare the clinical and biological characteristics of seropositive and seronegative cases. Patients and Methods. A cross-sectional study was carried out on 276 T1D patients including 109 adults and 167 pediatric cases. The screening for CD was performed by an Elisa IgA anti-tissue transglutaminase antibody (tTGA) testing, combined with IgA quantification by nephelometry. Positive-IgA-tTGA cases were secondly tested for anti-endomysial antibodies (EMA) using an immunofluorescence technique, and the IgA deficiency cases were screened for IgG-tTGA. Patients with low positive tTGA titers underwent HLA-DQ2/DQ8 typing. Sociodemographic and clinical data of the patients were collected using a hetero-administered questionnaire. The comparison of clinical and biological data between seropositive and seronegative diabetics was done using independent T, Mann–Whitney U, chi-squared, and Fisher tests, which were considered significant if p value <0.05. Results. The prevalence of CD-specific auto-antibodies was estimated to be 9.1% (IC = 95%), with 25 positive cases in tTGA and EMA testing. Eight cases displayed low titers of IgA-tTGA, among which 4 were positive for HLA-DQ2, 1 for HLA-DQ8, and 1 for both DQ2 and DQ8. The other 2 cases had a biopsy-proven CD. Compared to seronegative patients, seropositive cases had a higher percentage of associated autoimmune disorders (16% vs. 2.4%, p=0.008), with a significant lower height Z-scores (median: −0.90 (−3.93 to 0.95) vs. −0.51 (−4.54 to 2.18), p=0.029) and a higher HbA1c level (median: 11.30% (7.31 to 16.00) vs. 9.30% (4.40 to17.31), p=0.022). Conclusion. The current study gave evidence of a high prevalence of CD specific auto-antibodies in T1D population. The co-existence of these two conditions was associated with a poor glycemic control, a lower height, and other autoimmune diseases. These findings may suggest the necessity of a systematic screening of CD in T1D patients.


2001 ◽  
Vol 47 (11) ◽  
pp. 2023-2028 ◽  
Author(s):  
Mabel Aleanzi ◽  
Ana María Demonte ◽  
Cecilia Esper ◽  
Silvia Garcilazo ◽  
Marta Waggener

Abstract Background: Selective deamidation of glutamine residues by tissue transglutaminase (tTG) turns gliadin peptides into stronger activators of T cells from celiac disease (CD) patients. We examined the possibility that these modified peptides could be more specific epitopes for circulating antibodies than are native peptides. Methods: Two native synthetic peptides and their respective modified sequences were used as antigens for ELISA assays: peptide-1, with residues 56–75 of α-type gliadin; and peptide-2, with residues 134–153 of γ-type gliadin. We examined 40 CD patients [31 not being treated with a gluten-free diet (GFD) and 9 being treated with a GFD] and 30 non-CD patients. Results: An enhanced response against deamidated peptides was observed in 4 (IgA) and 22 (IgG) of 31 untreated CD patients for peptide-1 and in 25 (IgA) and 29 (IgG) patients for peptide-2. Higher anti-gliadin antibody and anti-tTG IgA concentrations correlated with increased IgA reactivity to modified peptides. Among the nine treated CD patients, eight also displayed an improved IgG signal for the deamidated sequence. Deamidation of peptides did not increase the reactivity of non-CD sera. Conclusions: Selective deamidation specifically increases circulating antibody recognition of gliadin peptides in CD patients. This suggests that deamidated gliadin peptides are more specific CD B-cell epitopes than native peptides; this finding may be relevant for designing improved diagnostic tests.


2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Kristina Baraba Dekanić ◽  
Ivona Butorac Ahel ◽  
Lucija Ružman ◽  
Jasmina Dolinšek ◽  
Jernej Dolinšek ◽  
...  

Introduction. Celiac disease (CD) is an autoimmune disease triggered by gluten in genetically predisposed individuals. Despite the increasing prevalence of CD, many patients remain undiagnosed. Standard serology tests are expensive and invasive, so several point-of-care tests (POC) for CD have been developed. We aimed to determine the prevalence of CD in first-grade pupils in Primorje-Gorski Kotar County, Croatia, using a POC test. Methods. A Biocard celiac test that detects IgA antibodies to tissue transglutaminase in whole blood was used to screen for celiac disease in healthy first-grade children born in 2011 and 2012 who consumed gluten without restrictions. Results. 1478 children were tested, and none of them were tested positive with a rapid test. In 10 children (0,6%), IgA deficiency has been suspected; only 4 of them agreed to be tested further for total IgA, anti-tTG, and anti-DGP antibodies. IgA deficiency was confirmed in 3 patients, and in all 4 children, CD has been excluded. Conclusion. Our results have not confirmed the usefulness of the POC test in screening the general population of first-grade schoolchildren. Further research is needed to establish the true epidemiology of CD in Primorje-Gorski Kotar County and to confirm the value of the rapid test in comparison with standard antibody CD testing.


2009 ◽  
Vol 55 (1) ◽  
pp. 150-157 ◽  
Author(s):  
Daniela Basso ◽  
Graziella Guariso ◽  
Paola Fogar ◽  
Alessandra Meneghel ◽  
Carlo-Federico Zambon ◽  
...  

AbstractBackground: AGA IgA II and AGA IgG II have recently been suggested as reliable tools for celiac disease (CD) diagnosis. We compared their utility for diagnosis and monitoring CD in children with that of tTG IgA, an established CD marker.Methods: We studied a cohort of 161 CD and 129 control children in whom CD was histologically confirmed or ruled out. We followed 37 children with CD on a gluten-free diet for 12–84 months. In fasting sera, we measured AGA IgA II, AGA IgG II, and tTG IgA using ELISAs.Results: The best sensitivity (92.5%), specificity (97.6%), positive predictive value (98%), and negative predictive value (91.2%) were obtained using tTG IgA. AGA IgG II correctly identified 3 of 3 children with CD with total IgA deficiency who had negative AGA IgA II and tTG IgA results. In children &lt;2 years old without total IgA deficiency, AGA IgG II and tTG IgA performed equally well (sensitivity 96.4% and specificity 100%). AGA IgA II, AGA IgG II, and tTG IgA concentrations diminished significantly (P &lt; 0.0001) after 1 year of a gluten-free diet, reaching values below the cutoff in 87%, 70%, and 51% of cases, respectively.Conclusions: The best available index for diagnosing CD in children was tTG IgA. In infants &lt;2 years old, AGA IgG II performed as well as tTG IgA in cases without total IgA deficiency and allowed detection of CD when total IgA was &lt;0.06 g/L. Gluten-free diet monitoring can be achieved using any of the studied serum markers.


2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e14-e14
Author(s):  
Michelle Gould ◽  
Herbert Brill ◽  
Margaret Marcon ◽  
Catharine Walsh

Abstract BACKGROUND Celiac disease (CD) is an autoimmune enteropathy triggered by gliadin. The gold standard for diagnosis is small bowel biopsy. Screening with serologic markers to identify endoscopic candidates is commonly completed by paediatricians. The most common serologic marker used for screening is IgA anti-Tissue Transglutaminase (TTG) antibodies. Antibodies to deamidated gliadin peptide (DGP) is a newer assay with studies demonstrating a diagnostic performance similar to anti-TTG. In Canada, this assay has been added to many laboratory’s celiac screening panels. There is little evidence however regarding the usefulness of an isolated positive anti-DGP result in paediatric patients and no study has systematically assessed the presence of biopsy proven CD in solely anti-DGP positive paediatric patients. OBJECTIVES We sought to determine the positive predictive value of anti-DGP for biopsy proven CD in paediatric patients with negative TTG IgA testing. DESIGN/METHODS A multi-center retrospective review of children referred to three centers in Ontario, Canada between January 2015 and December 2016 who had isolated anti-IgG DGP positive CD serology was completed. To be included, patients required serology positive for DGP IgG and negative for all other celiac serologic tests, as well as a duodenal biopsy while on a gluten-containing diet. The positive predictive value of isolated anti-DGP was calculated. RESULTS A total of 83 patients were identified with anti-DGP positive, anti-TTG negative serology. Of these, 40 patients underwent endoscopy. Only 1 patient had findings consistent with CD on biopsy (Marsh 3B histology), yielding a positive predictive value of 2.5%. This patient was IgA deficient. Amongst the cohort of IgA sufficient patients (N=25), the positive predictive value of anti-DGP serology was 0%. One additional patient who was IgA sufficient had findings in keeping with Marsh 2 histology, but repeat TTG and DGP testing was negative. Five patients were found to be IgA deficient at the time of serologic testing, 25 were IgA sufficient and 10 did not have a measured IgA. CONCLUSION Isolated positive DGP IgG serology has a poor positive predictive value for CD, especially in IgA sufficient individuals. For this reason, DGP IgG testing should not be completed as part of the initial screening for celiac disease in the paediatric population unless a compelling reason, such as IgA deficiency or age under 2 years, is present, in order to prevent unnecessary invasive follow-up testing and costs to patients and the health care system.


Author(s):  
Karsten Conrad ◽  
Dirk Roggenbuck ◽  
Annelore Ittenson ◽  
Dirk Reinhold ◽  
Thomas Buettner ◽  
...  

AbstractThis study investigated whether a dot immunoassay (DIA) can provide simultaneous detection of anti-tissue transglutaminase (tTG), anti-deamidated gliadin (DG) and total IgA antibodies, as required in the work-up of celiac disease (CD) patients.Celiac disease patients (n=111) consecutively diagnosed from 2001 to 2011 at the Children’s Hospital and Institute of Immunology (Technical University Dresden) were tested for anti-tTG, anti-DG and total IgA by enzyme-linked immunosorbent assay (ELISA) and DIA retrospectively. Blood donors (n=45) and non-CD individuals with low IgA serum levels (n=8) were included as controls. Antibodies to endomysial antigens (EmA) were assessed by indirect immunofluorescence (IIF).Four (3.6%) of 111 CD patients demonstrated an IgA deficiency with total IgA below 50 mg/L by ELISA. Total IgA of the 107 IgA-non-deficient CD patients varied from 70 to 6000 mg/L. All four IgA-deficient CD patients were detected by a reduced reaction control of DIA and demonstrated positive anti-tTG or anti-DG IgG by DIA or ELISA. Detection of anti-tTG and anti-DG by DIA and ELISA showed a very good agreement (IgA: κ=0.972, 0.856, respectively; IgG: 0.921, 0.895, respectively).Immunodot assay is a reliable and easy-to-use technique for the detection of IgA-deficient CD patients. Simultaneous assessment of anti-tTG and anti-DG IgA antibodies, and IgA deficiency by DIA can improve the efficacy of CD serology.


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