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Histogram comparing standard diagnosis by IgG anti-tTG ELISA assay and/or biopsy and/or follow-up to CD-LFIA test results.
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![Figure 2: Diagnostic performance of CD-LFIA [with 95% CI].](profile/Cecile-Duvanel/publication/267932585/figure/fig1/AS:272548629839886@1441992065250/Diagnostic-performance-of-CD-LFIA-with-95-CI_Q320.jpg)
Background
The serological diagnosis of celiac disease (CD) often relies on the presence of anti-tissue transglutaminase (tTG) IgA autoantibodies. Patients suffering from selective IgA deficiency (IgAD) are often not aware of their IgA deficiency and are tested as CD negative, delaying considerably the diagnosis. The detection of IgG against deamid...
Contexts in source publication
Context 1
... on the "standard diagnosis" (IgG anti-tTG positive serology, biopsy result and patient follow-up), eight (8) new cases of CD were found, all were correctly identified by CD-LFIA (Figure 1). Their histology revealed subtotal (n = 1; Marsh 3b) or complete villous atrophy (n = 7; Marsh 3c). ...
Context 2
... this patient had no follow-up and no biopsy was conducted. Both patients were further considered as false positive (Figure 1). ...
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Citations
... The development of portable, compact, and easy-to-handle tools entails significant advantages for its self-use by patients, as it allows direct detection or personalized monitoring of therapies usually with a small amount of a biological sample. Such is the case of the qualitative tests based on lateral flow immunochromatography (LFT) Sintomax ® (Augurix SA, Switzerland), Xeliac ® Test (Eurospital, Italy), and Biocard ™ celiac test (AniBiotech ® , Vantaa, Finland) [22][23][24][25]. These companies have developed qualitative, direct, rapid, and easy tests that support the monitoring or the diagnosis of the disease by the end-user. ...
Celiac disease (CD) is a chronic autoimmune disorder induced in genetically susceptible individuals by the ingestion of gluten from wheat, rye, barley, or certain varieties of oats. A careful diet follow-up is necessary to avoid health complications associated with long-term gluten intake by the celiac patients. Small peptides (GIP, gluten immunogenic peptides) derived from gluten digestion, which are excreted in the urine and feces, have emerged as promising biomarkers to monitor gluten intake. We have implemented a simple and sensitive label-free point-of-care (POC) device based on surface plasmon resonance for the direct detection of these biomarkers in urine. The assay employs specific monoclonal antibodies and has been optimized for the detection of the 33-mer α2-gliadin, known as the main immunogenic peptide of wheat gluten, and for the detection of GIP. Direct detection in undiluted urine has been accomplished by using biosensing chips containing a robust and stable biorecognition layer, obtained after carefully optimizing the biofunctionalization protocol. Excellent limits of detection have been reached (1.6–4.0 ng mL−1 using mAb G12 and A1, respectively), which ensures the detection of gluten peptides even when the gluten intake is around the maximum tolerable amount in the digestive tract (< 50 mg) for celiac individuals. No sample pretreatment, extraction, or dilution is required, and the analysis takes less than 15 min. The assays have excellent reproducibility‚ as demonstrated by measuring spiked urine samples containing the same target concentration using different biofunctionalized chips prepared and stored at different periods of time (i.e., CV% of 3.58% and 11.30%, for G12- and A1-based assays, respectively). The assay has been validated with real samples. These features pave the way towards an end-user easy-to-handle biosensor device for the rapid monitoring of gluten-free diet (GFD) and follow-up of the health status in celiac patients.
... The intended use is as a first-line screening test for celiac disease antibodies in nonspecialist settings. Previously, Simtomax ® has primarily been tested among patients representing high-prevalence populations as in gastroenterological specialist settings [20,[22][23][24][25][26][27][28]. The accuracy of Simtomax ® has not yet been tested in a fertility treatment program with an expected lower prevalence of celiac disease. ...
... The PPV and NPV are dependent on the prevalence of the disease in the population in which the test is used, and, therefore, the test can have different predictive values in different settings, e.g., a nonspecialist versus a specialist setting. Previously reported PPV and NPV for the Simtomax ® POC test from pediatric or gastroenterological settings [25,26] cannot be expected to be the same in a population of infertile patients with an expected lower prevalence of celiac disease. With an NPV of 99.3% (95% CI 98.1-99.8), ...
Background:
Screening for celiac disease among infertile patients has been suggested. Several rapid point-of-care (POC) tests aimed at detecting celiac disease antibodies have been developed. It has been suggested that these POC tests can be implemented as a replacement for standard laboratory tests.
Objective:
To evaluate the diagnostic accuracy of a POC test (Simtomax®) that detects celiac disease antibodies compared with standard laboratory tests when screening for celiac disease among patients referred for fertility treatment in 2 Danish fertility clinics.
Methods:
Serum samples were analyzed for IgA anti-tissue transglutaminase (TGA) as the reference standard test with a cutoff of ≥7 kU/L and by the index POC test based on IgA and IgG antibodies against deamidated gliadin peptides (DGP). In IgA deficiency, the reference standard test was IgG DGP with a cutoff of ≥7 kU/L. Participants answered a questionnaire on gluten intake, symptoms, and risk factors. Diagnostic confirmation was made by duodenal biopsies. IgA TGA/IgG DGP were used as the reference standard to calculate positive and negative predictive values.
Results:
A total of 622 men and women (51.6%) were enrolled during 2015. The reference standard IgA TGA/IgG DGP was positive in 7 participants (1.1% [95% CI 0.5-2.3]) and the POC test was positive in 84 participants (13.5% [95% CI 10.9-16.4]), 3 of whom also had positive reference standard tests. This yields a sensitivity of the index POC test of 42.9% (95% CI 9.9-81.6) and a specificity of 86.8% (95% CI 83.9-89.4). Positive and negative predictive values were 3.57% (95% CI 0.7-10.1) and 99.3% (95% CI 98.1-99.8).
Conclusion:
The sensitivity of the POC test was low; however, the specificity was moderately good. The POC test had a high negative predictive value in this low prevalent population but missed 1 patient with biopsy-confirmed celiac disease. However, because of many false-positive tests, it cannot be recommended as replacement for standard laboratory tests but rather as a triage test to decide if the standard serology tests should be performed.
... Immunoglobulin A (IgA) is the isotype typically determined as the target analyte for serological CD screening, but IgA-deficient CD patients are not identified by IgA serology; in these patients, immunoglobulin G (IgG) anti-tTG antibodies are investigated [8]. However, several clinical studies have shown that IgG anti-tTG antibodies are not as sensitive and specific as the IgA anti-tTG antibodies, and the use of the indirect immunofluorescence assay to detect anti-endomysium antibodies (EMA) in daily practice is limited by subjective interpretations [9]. The cut-off value for IgG anti-tTG antibodies measurement is 7 U/mL. ...
Celiac disease (CD) is a gluten-dependent autoimmune disorder affecting a significant percentage of the general population, with increasing incidence particularly for children. Reliable analytical methods suitable for the serological diagnosis of the disorder are urgently required for performing both the early diagnosis and the follow-up of a patient adhering to a gluten-free diet. Herein we report on the preparation and application of a novel electrochemical immunosensor based on the use of ensembles of gold nanoelectrodes (NEEs) for the detection of anti-tissue transglutaminase (anti-tTG), which is considered one reliable serological marker for CD. To this end, we take advantage of the composite nature of the nanostructured surface of membrane-templated NEEs by functionalizing the polycarbonate surface of the track-etched membrane with tissue transglutaminase. Incubation of the functionalized NEE in anti-tTG samples results in the capture of the anti-tTG antibody. Confirmation of the recognition event is achieved by incubating the NEE with a secondary antibody labelled with horseradish peroxidase (HRP): in the presence of H2O2 as substrate and hydroquinone as redox mediator, an electrocatalytic current is indeed generated whose increment is proportional to the amount of anti-tTG captured from the sample. The optimized sensor allows a detection limit of 1.8 ng mL−1, with satisfactory selectivity and reproducibility. Analysis of serum samples from 28 individuals, some healthy and some affected by CD, furnished analytical results comparable with those achieved by classical fluoroenzyme immunoassay (FEIA). We note that the NEE-based immunosensor developed here detects the IgG isotype of anti-tTG, while FEIA detects the IgA isotype, which is not a suitable diagnostic marker for IgA-deficient patients.
... This ensured that no false negative cases of CD would be missed. This methodology contributed to a major difference to most POCT studies for CD, where only patients with positive antibodies (either POCT or serology) were biopsied [32][33][34][35][36][37]. Additionally, some POCT studies measured the sensitivities against serology rather than duodenal histology as the reference standard [35,38,39]. ...
... [17,18]. A much higher CD prevalence is a common limitation in previous POCT studies [34,40,41]. This tertiary referral bias restricts the generalizability of their findings. ...
Objectives:
Celiac disease (CD) is common yet under-detected. A point of care test (POCT) may improve CD detection. We aimed to assess the diagnostic performance of an IgA/IgG-deamidated gliadin peptide (DGP)-based POCT for CD detection, patient acceptability, and inter-observer variability of the POCT results.
Methods:
From 2013-2017, we prospectively recruited patients referred to secondary care with gastrointestinal symptoms, anemia and/or weight loss (group 1); and patients with self-reported gluten sensitivity with unknown CD status (group 2). All patients had concurrent POCT, IgA-tissue transglutaminase (IgA-TTG), IgA-endomysial antibodies (IgA-EMA), total IgA levels, and duodenal biopsies. Five hundred patients completed acceptability questionnaires, and inter-observer variability of the POCT results was compared among five clinical staff for 400 cases.
Results:
Group 1: 1000 patients, 58.5% female, age 16-91, median age 57. Forty-one patients (4.1%) were diagnosed with CD. The sensitivities of the POCT, IgA-TTG, and IgA-EMA were 82.9, 78.1, and 70.7%; the specificities were 85.4, 96.3, and 99.8%. Group 2: 61 patients, 83% female; age 17-73, median age 35. The POCT had 100% sensitivity and negative predictive value in detecting CD in group 2. Most patients preferred the POCT to venepuncture (90.4% vs. 2.8%). There was good inter-observer agreement on the POCT results with a Fleiss Kappa coefficient of 0.895.
Conclusions:
The POCT had comparable sensitivities to serology, and correctly identified all CD cases in a gluten sensitive cohort. However, its low specificity may increase unnecessary investigations. Despite its advantage of convenience and rapid results, it may not add significant value to case finding in an office-based setting.
... Most of the POCTs detect TTG using lateral fl ow immunochromotography, such as Biocard, Celiac Quick Test, and Stick CD1 and 2, with the exception of Simtomax, which detects deamidated gliadin peptide (DGP) antibodies. Th ere is an abundance of studies investigating the performance of POCTs in the diagnosis of CD, with sensitivities of the aforementioned POCTs reported to be 58-100% (32)(33)(34)(35)(36)(37)(38)(39)(40). A recent head to head trial of Simtomax, Biocard, and Celiac Quick Test demonstrated that Simtomax outperformed the other two, with sensitivities of 94.4%, 72.2%, and 77.8%, respectively ( 32 ). ...
Objectives:
Mucosal healing is important in celiac disease (CD) for the prevention of complications. However, obtaining duodenal biopsies is invasive, and there is currently no reliable surrogate marker for histological remission in clinical practice. We aimed to assess the role of a point-of-care test (POCT) based on IgA/IgG-deamidated gliadin peptide, in detecting persistent villous atrophy (VA) in CD.
Methods:
We prospectively recruited patients with CD attending endoscopy for the assessment of histological remission. All patients had IgA-endomysial (EMA) antibodies, IgA-tissue transglutaminase (TTG) antibodies, and the POCT performed, and completed a validated dietary adherence questionnaire. A gastroscopy was performed in all patients, with four biopsies taken from the second part of the duodenum and one from the duodenal bulb. We compared the diagnostic performance of the surrogate markers against duodenal histology as the reference standard.
Results:
A total of 217 patients with CD (70% female, age range 16-83 years, median age 53 years) on a gluten-free diet (median duration 6 years) were recruited from 2013 to 2017. Eighty-five (39.2%) patients had persistent VA. The sensitivities of the POCT, TTG, EMA, and the adherence score in detecting VA were 67.1%, 44.7%, 37.7%, and 24.7% respectively (P=0.0005). The combination of the POCT and adherence score only marginally increased the sensitivity to 70.6% (59.7-80.0%).
Conclusions:
The sensitivity of the POCT was higher than the other surrogate markers in predicting VA. A POCT may provide the additional advantage of an immediate objective assessment of mucosal healing at the time of an office-based follow-up consultation.Am J Gastroenterol advance online publication, 10 October 2017; doi:10.1038/ajg.2017.357.
... The use of POC testing is an alternative to standard laboratory assays and is an approach which offers fast results and is minimally invasive. In children, a DGP-based POCT showed results which were highly concordant with laboratory tTG testing (23,24), including IgA deficient patients (25). In patients with CD-related symptoms of a wide range of ages (1.8-79.2 ...
... The performance of the DGP-based POCT studied here has been previously assessed in paediatric cohorts (23)(24)(25), but was compared to conventional tTG lab serology and not to diagnostic ESPGHAN criteria. In a large pediatric population and in a second cohort of IgA deficient children, a high negative predictive value was found of 99% and 100%, respectively. ...
... Our data suggest that the POCT may be the most accurate method in children younger than ten years of age. However, no similar observation was reported by Bienvenu et al. (23,25). Moreover, Kurppa et al. (30) found a high sensitivity for IgA/IgG-DGP antibodies in detecting early-stage CD when the villous morphology has not been affected yet. ...
Objective:
The objective of the study was to assess the effectiveness of a point-of-care test (POCT) based on deamidated gliadin peptides (DGP) compared to the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) criteria diagnosis in the early detection of celiac disease (CD) in pediatric patients.
Methods:
One hundred children (≤ 18 years) with suspected CD were selected, including siblings of celiac children that underwent gastroscopy for other gastrointestinal conditions. Patients with severe disease, following a gluten-free diet (GFD), with gastrointestinal bleeding, coagulopathy and infections in the last month were excluded. All children were evaluated with a POCT that detects immunoglobulin A (IgA) and immunoglobulin G (IgG) antibodies to DGP and total IgA. The POCT results were compared to CD diagnosis according to current ESPGHAN criteria. This involved the detection of IgA tissue transglutaminase (tTG) antibodies, the results of an intestinal biopsy and genetic testing.
Results:
The prevalence of CD found in the present study was 48% (95% confidence interval in parenthesis 37.9-58.2%). The results of the POCT were concordant with the CD diagnosis made according to ESPGHAN criteria: 95.8% (85.7-99.4%) sensitivity, 98.1% (89.7-99.7%) specificity, 97.9% (88.7-99.6%) positive predictive value and 96.2% (87.0-99.4%) negative predictive value. Positive and negative likelihood ratios were 49.8 (7.2-347.5) and 0.04 (0.01-0.17), respectively. The POCT showed a 100% diagnostic accuracy in children younger than ten years of age. In total, three discordant results were found.
Conclusion:
Due to the high diagnostic accuracy in the pediatric population, the POCT can be considered as an effective tool for the early diagnosis of CD, especially in patients younger than ten years of age.
... These POCTs use lateral flow immunochromatography to detect celiac antibodies and provide rapid results within 10 min. Most studies delivered promising results similar to serology, but common limitations include high celiac disease prevalence populations [70,71], positive ascertainment bias where only individuals with positive antibodies underwent duodenal biopsies [72][73][74][75] and some studies measuring the POCT performance against serology rather than duodenal biopsies [76,77]. The latter two methodological flaws meant that false negative cases may be missed, elevating the reported sensitivities of the POCTs. ...
... Furthermore, in order to reduce selection bias, all patients underwent duodenal biopsies irrespective of their serology or Simtomax results. This sets our study apart from the three out of four published Simtomax studies, [25][26][27] where only patients with a positive serology or Simtomax test went on to have duodenal biopsies, which could potentially lead to a positive ascertainment bias and falsely elevated sensitivities. This limitation is also common in previous studies on the sensitivities of coeliac serology. ...
... Our study demonstrated excellent sensitivity and negative predictive value of Simtomax in iron deficiency, and its performance was comparable to both IgA-EMA and IgA-TTG. This is consistent with two other studies testing Simtomax in high risk groups performed by Benkebil et al. in 2013 [26] (100 % sensitivity for coeliac disease in a high risk population) and Bienvenu et al. in 2014 [27] (100 % sensitivity and NPV for coeliac disease in IgA deficient children, median age 8.4). However, Bienvenu et al. 2012 [25] showed that the sensitivity of Simtomax to be slightly lower at 93.1 % when tested on a paediatric population with clinical suspicion of coeliac disease, although it should be noted that this sensitivity was measured against TTG as the reference standard rather than duodenal histology. ...
Unfortunately, after publication of this article [1] it was noticed that several authors were missing their middle initials. The corrected author list can be seen above and the original article has been updated to reflect this change.
... Furthermore, in order to reduce selection bias, all patients underwent duodenal biopsies irrespective of their serology or Simtomax results. This sets our study apart from the three out of four published Simtomax studies, [25][26][27] where only patients with a positive serology or Simtomax test went on to have duodenal biopsies, which could potentially lead to a positive ascertainment bias and falsely elevated sensitivities. This limitation is also common in previous studies on the sensitivities of coeliac serology. ...
Background
International guidelines recommend coeliac serology in iron deficiency anaemia, and duodenal biopsy for those tested positive to detect coeliac disease. However, pre-endoscopy serology is often unavailable, thus committing endoscopists to take routine duodenal biopsies. Some endoscopists consider duodenal biopsy mandatory in anaemia to exclude other pathologies. We hypothesise that using a point of care test at endoscopy could fill this gap, by providing rapid results to target anaemic patients who require biopsies, and save costs by biopsy avoidance. We therefore assessed three key aspects to this hypothesis: 1) the availability of pre-endoscopy serology in anaemia; 2) the sensitivities and cost effectiveness of pre-endoscopy coeliac screening with Simtomax in anaemia; 3) whether other anaemia-related pathologies could be missed by this targeted-biopsy approach. Methods
Group 1: pre-endoscopy serology availability was retrospectively analysed in a multicentre cohort of 934 anaemic patients at 4 UK hospitals. Group 2: the sensitivities of Simtomax, endomysial and tissue-transglutaminase antibodies were compared in 133 prospectively recruited patients with iron deficiency anaemia attending for a gastroscopy. The sensitivities were measured against duodenal histology as the reference standard in all patients. The cost effectiveness of Simtomax was calculated based on the number of biopsies that could have been avoided compared to an all-biopsy approach. Group 3: the duodenal histology of 153 patients presenting to a separate iron deficiency anaemia clinic were retrospectively reviewed. ResultsIn group 1, serology was available in 361 (33.8 %) patients. In group 2, the sensitivity and negative predictive value (NPV) were 100 % and 100 % for Simtomax, 96.2 % and 98.9 % for IgA-TTG, and 84.6 % and 96.4 % for EMA respectively. In group 3, the duodenal histology found no causes for anaemia other than coeliac disease. Conclusion
Simtomax had excellent diagnostic accuracy in iron deficiency anaemia and was comparable to conventional serology. Duodenal biopsy did not identify any causes other than coeliac disease for iron deficiency anaemia, suggesting that biopsy avoidance in Simtomax negative anaemic patients is unlikely to miss other anaemia-related pathologies. Due to its 100 % NPV, Simtomax could reduce unnecessary biopsies by 66 % if only those with a positive Simtomax were biopsied, potentially saving £3690/100 gastroscopies. Trial registrationThe group 2 study was retrospectively registered with clinicaltrials.gov. Trial registration date: 13th July 2016; Trial registration number: NCT02834429.
... In this first study the point-of-care test yielded a sensitivity of 93% and a specificity of 95% compared with the TG2ab -based ELISA assay [97]. The DGP test has since been further tested in a number of studies and the results have been fairly promising [97][98][99][100]. As a limitation, there have been false-positive results even in subjects with genetics inappropriate for celiac disease, and currently the test is recommended to be used only by health care professionals [97]. ...
The diagnosis of celiac disease has long been based on the demonstration of gluten-induced small-bowel mucosal damage. However, due to the constantly increasing disease prevalence and limitations in the histology-based criteria there is a pressure towards more serology-based diagnostics. The serological tools are being improved and new non-invasive methods are being developed, but the constantly refined endoscopic and histologic techniques may still prove helpful. Moreover, growing understanding of the disease pathogenesis has led researchers to suggest completely novel approaches to celiac disease diagnostics regardless of disease activity. In this review, we will elucidate the most recent development and possible future innovations in the diagnostic techniques for celiac disease.
