scholarly journals Celiac Disease and IgA Deficiency: Complications of Serological Testing Approaches Encountered in the Clinic

2008 ◽  
Vol 54 (7) ◽  
pp. 1203-1209 ◽  
Author(s):  
Kelly E McGowan ◽  
Martha E Lyon ◽  
J Decker Butzner
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
False Negative ◽  
Transglutaminase 2 ◽  
Iga Deficiency ◽  
Intestinal Biopsy ◽  
Serological Testing ◽  
Gastrointestinal Pathology ◽  
Serum Iga ◽  
Testing Algorithms

AbstractBackground: IgA deficiency causes false-negative IgA-based celiac serology results in patients with celiac disease. Using a case-finding strategy, we examined the prevalence of IgA deficiency, physician evaluation, and management of IgA deficiency during serological testing for celiac disease.Methods: We reviewed consecutive IgA-endomysial antibody (EMA) and serum IgA results from the laboratory database over 17 months. We cross-referenced seronegative patients with IgA deficiency (IgA <0.06 g/L) to the pathology database to evaluate intestinal biopsy results. Ordering physicians received a questionnaire regarding the management of seronegative patients with IgA deficiency who had no biopsy record.Results: Among the 9533 patients tested for IgA-EMA, 4698 (49%) were tested for IgA deficiency. IgA deficiency occurred in 35 of 4698 (0.75%) patients screened for IgA deficiency. Only 19 of 35 (54%) IgA-deficient patients were diagnosed appropriately with either intestinal biopsy (17 patients) or measurement of IgG-tissue transglutaminase (2 patients). Thirteen (76%) of the 17 IgA-deficient patients who underwent upper endoscopy with or without colonoscopy displayed gastrointestinal pathology on biopsies, including 3 (18%) with celiac disease. No further evaluation to exclude celiac disease was performed for the remaining 16 of 35 (46%) IgA-deficient, EMA-negative patients because of inappropriate management (6 patients), administrative error (7 patients), or patient/physician refusal (3 patients).Conclusions: IgA deficiency occurred in 1:131 patients tested for celiac disease, and celiac disease occurred in 1:6 of those properly evaluated. Inadequate evaluation of IgA deficiency while testing for celiac disease occurred frequently and resulted in the underdiagnosis of both. Changes in testing algorithms and reporting of results were made to improve testing for celiac disease and IgA deficiency.

scholarly journals Diagnostic Accuracy of Ten Second-Generation (Human) Tissue Transglutaminase Antibody Assays in Celiac Disease

2004 ◽  
Vol 50 (11) ◽  
pp. 2125-2135 ◽  
Author(s):  
Britta Van Meensel ◽  
Martin Hiele ◽  
Ilse Hoffman ◽  
Severine Vermeire ◽  
Paul Rutgeerts ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Diagnostic Accuracy ◽  
Sensitivity And Specificity ◽  
Second Generation ◽  
Tissue Transglutaminase ◽  
Iga Deficiency ◽  
Intestinal Biopsy ◽  
Technical Performance ◽  
Antibody Assays ◽  
Endomysium Antibodies

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.

scholarly journals Celiac Disease and Immunoglobulin A Deficiency: How Effective Are the Serological Methods of Diagnosis?

2002 ◽  
Vol 9 (6) ◽  
pp. 1295-1300 ◽  
Author(s):  
V. Kumar ◽  
M. Jarzabek-Chorzelska ◽  
J. Sulej ◽  
Krystyna Karnewska ◽  
T. Farrell ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Pediatric Patients ◽  
Tissue Transglutaminase ◽  
False Negative ◽  
Immunoglobulin A ◽  
Iga Deficiency ◽  
Igg Antibodies ◽  
Serological Tests ◽  
Asymptomatic Patients ◽  
Antibody Tests

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.

scholarly journals Celiac disease: Understandings in diagnostic, nutritional, and medicinal aspects

2021 ◽  
Vol 35 ◽  
pp. 205873842110087
Author(s):  
Taoufik Ben Houmich ◽  
Brahim Admou
Keyword(s):  
Celiac Disease ◽  
Villous Atrophy ◽  
Current Trend ◽  
Diagnostic Delay ◽  
General Medicine ◽  
Iga Deficiency ◽  
Health Concern ◽  
Intestinal Biopsy ◽  
Antibody Testing ◽  
Main Challenge

Celiac disease (CD) is characterized by clinical polymorphism, with classic, asymptomatic or oligosymptomatic, and extra-intestinal forms, which may lead to diagnostic delay and exposure to serious complications. CD is a multidisciplinary health concern involving general medicine, pediatric, and adult gastroenterology, among other disciplines. Immunology and pathology laboratories have a fundamental role in diagnosing and monitoring CD. The diagnosis consists of serological testing based on IgA anti-transglutaminase (TG2) antibodies combined with IgA quantification to rule out IgA deficiency, a potential misleading factor of CD diagnosis. Positive TG2 serology should be corroborated by anti-endomysium antibody testing before considering an intestinal biopsy. Owing to multiple differential diagnoses, celiac disease cannot be confirmed based on serological positivity alone, nor on isolated villous atrophy. In children with classical signs or even when asymptomatic, with high levels of CD-linked markers and positive HLA DQ2 and/or DQ8 molecules, the current trend is to confirm the diagnosis on basis of the non-systematic use of the biopsy, which remains obligatory in adults. The main challenge in managing CD is the implementation and compliance with a gluten-free diet (GFD). This explains the key role of the dietitian and the active participation of patients and their families throughout the disease-management process. The presence of the gluten in several forms of medicine requires the sensitization of physicians when prescribing, and particularly when dispensing gluten-containing formulations by pharmacists. This underlines the importance of the contribution of the pharmacist in the care of patients with CD within the framework of close collaboration with physicians and nutritionists.

scholarly journals Testing for Gluten-Related Disorders in Clinical Practice: The Role of Serology in Managing the Spectrum of Gluten Sensitivity

2011 ◽  
Vol 25 (4) ◽  
pp. 193-197 ◽  
Author(s):  
David Armstrong ◽  
Andrew C Don-Wauchope ◽  
Elena F Verdu
Keyword(s):  
Celiac Disease ◽  
Serological Test ◽  
Tissue Transglutaminase ◽  
Immunoglobulin A ◽  
Intestinal Damage ◽  
Gluten Sensitivity ◽  
Serological Testing ◽  
Diet Compliance ◽  
At Risk Populations ◽  
Irritable Bowel

Immunoglobulin A tissue transglutaminase is the single most efficient serological test for the diagnosis of celiac disease. It is well known that immunoglobulin A tissue transglutaminase levels correlate with the degree of intestinal damage, and that values can fluctuate in patients over time. Serological testing can be used to identify symptomatic individuals that need a confirmatory biopsy, to screen at-risk populations or to monitor diet compliance in patients previously diagnosed with celiac disease. Thus, interpretation of serological testing requires consideration of the full clinical scenario. Antigliadin tests are no longer recommended for the diagnosis of classical celiac disease. However, our understanding of the pathogenesis and spectrum of gluten sensitivity has improved, and gluten-sensitive irritable bowel syndrome patients are increasingly being recognized. Studies are needed to determine the clinical utility of antigliadin serology in the diagnosis of gluten sensitivity.

scholarly journals The Prevalence of Celiac Disease-Specific Auto-Antibodies in Type 1 Diabetes in a Moroccan Population

2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Ider Oujamaa ◽  
Majda Sebbani ◽  
Lahcen Elmoumou ◽  
Aïcha Bourrahouate ◽  
Rabiy El Qadiry ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Tissue Transglutaminase ◽  
Iga Deficiency ◽  
Cross Sectional Study ◽  
Biological Data ◽  
Cross Sectional ◽  
Systematic Screening ◽  
Lower Height ◽  
Hla Dq2

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.

scholarly journals Is There a Role of Using a Rapid Finger Prick Antibody Test in Screening for Celiac Disease in Children?

2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Kristina Baraba Dekanić ◽  
Ivona Butorac Ahel ◽  
Lucija Ružman ◽  
Jasmina Dolinšek ◽  
Jernej Dolinšek ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Point Of Care ◽  
Tissue Transglutaminase ◽  
Rapid Test ◽  
Antibody Test ◽  
First Grade ◽  
Iga Deficiency ◽  
Iga Antibodies ◽  
Point Of Care Tests

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.

scholarly journals SEROLOGICAL SCREENING FOR CELIAC DISEASE IN CHILDREN WITH COLCHICINE-RESISTANT FAMILIAL MEDITERRANEAN FEVER

2018 ◽  
Vol 55 (2) ◽  
pp. 175-178
Author(s):  
Yasin ŞAHIN ◽  
Kenan BARUT ◽  
Tufan KUTLU ◽  
Fugen Cullu COKUGRAS ◽  
Amra ADROVIC ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Familial Mediterranean Fever ◽  
Tissue Transglutaminase ◽  
Intestinal Biopsy ◽  
Control Group ◽  
Serological Screening ◽  
Iga Antibodies ◽  
Mediterranean Fever ◽  
Iga Antibody ◽  
Clinical Conditions

ABSTRACT BACKGROUND: Familial Mediterranean fever and celiac disease share some common clinical features such as abdominal pain, diarrhea, arthralgia and arthritis. Also, both of the diseases are associated with many inflammatory and autoimmune diseases. Previous studies have shown the association between familial Mediterranean fever (FMF) and different clinical conditions. OBJECTIVE: We aimed to investigate the relationship between celiac disease and colchicine-resistant familial Mediterranean fever (crFMF) disease. METHODS: This prospective study was conducted at the Department of Pediatric Gastroenterology and Pediatric Rheumatology from October 2015 to August 2016. A total of 24 patients with crFMF were included in the study. We used 60 sex- and age-matched healthy subjects as a control group. Levels of total IgA and tissue transglutaminase (tTG) IgA antibody were measured in both groups. Those with increased level of tTG IgA were tested for anti-endomysium IgA antibodies (EMA). Gastroduodenoscopy and intestinal biopsy were planned for a definite diagnosis of celiac disease in patients with positive EMA. RESULTS: Of the 24 patients in this study, 18 (75.0%) were female. Only 4 (16.6%) of 24 patients were positive for tTG IgA. Patients with positive tTG IgA were then tested for EMA IgA antibodies and none of them had a positive result. Only one (1.6%) subject from the control group was positive for tTG IgA but EMA positivity was not detected. CONCLUSION: We did not found celiac disease in 24 children with crFMF. Since crFMF disease is rarely seen in general population, further studies with more patients are needed to provide more precise interpretation.

scholarly journals THE USEFULNESS OF DEAMIDATED GLIADIN PEPTIDE IN SCREENING PEDIATRIC PATIENTS FOR CELIAC DISEASE

2018 ◽  
Vol 23 (suppl_1) ◽  
pp. e14-e14
Author(s):  
Michelle Gould ◽  
Herbert Brill ◽  
Margaret Marcon ◽  
Catharine Walsh
Keyword(s):  
Celiac Disease ◽  
Positive Predictive Value ◽  
Predictive Value ◽  
Tissue Transglutaminase ◽  
Paediatric Population ◽  
Iga Deficiency ◽  
Additional Patient ◽  
Serologic Marker ◽  
Paediatric Patients ◽  
Gliadin Peptide

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.

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 ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Blood Donors ◽  
Tissue Transglutaminase ◽  
Iga Deficiency ◽  
Diagnostic Sensitivity ◽  
Igg Antibodies ◽  
Diagnostic Specificity ◽  
Gliadin Peptides ◽  
Endomysium Antibodies ◽  
Monkey Esophagus

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.

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