Early diagnosis of celiac disease in IgA deficient children: contribution of a point-of-care test.

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 deamidated gliadin peptides (DGP) has high specificity and better sensitivity than IgG anti-tTG. A multi-analytic lateral-flow immunochromatographic assay (CD-LFIA) based on the detection of IgA and IgG anti-DGP and total IgA was shown to have a good diagnostic accuracy for CD. The aim of this study was to evaluate the clinical accuracy of its use in children suffering from IgAD. METHODS: 45 IgAD children ranging from 1.1 to 17.4 years and suspected of CD or having high CD risk factors were referred from outpatient clinics located in the area of Rhone-Alpes (France) to the Hospices Civils de Lyon, Paediatric Hospital-Gastroenterology-Hepatology- Nutrition Department for further CD investigations. The CD investigations, including the sample collection, were performed within the Paediatric Hospital-Gastroenterology-Hepatology- Nutrition Department, and the serological testing was performed at the Lyon-Sud Hospital-Immunology Laboratory. The diagnosis of CD was based on IgG anti-tTG serology, biopsy results and patient follow-up. The serum samples were retrospectively tested on the CD-LFIA test. RESULTS: A total of eight (8) patients were diagnosed as new CD. All were correctly identified by the CD-LFIA. The test yielded four (4) false positive results. Two patients with positive IgG anti-tTG were negative on CD-LFIA, but were classified as CD negative based on biopsy results and patient follow-up. The remaining 33 patients were found negative by both methods. The specificity and sensitivity of CD-LFIA was of 89.2% [74.6-97.0] and of 100% [63.1-100] respectively. The negative predictive value (NPV) was of 100% [89.4-100], and the Likelihood Ratio for Negative Test (LR-) was of 0 [0.0-0.91]. CONCLUSIONS: CD-LFIA is a useful, non-invasive and rapid tool to rule out CD in primary care paediatric patients having CD-related symptoms and IgAD. Patients having a positive CD-LFIA result could be then readily directed to secondary care setting for further evaluation by standard serology and biopsy.

Diagnostic accuracy of a new point-of-care screening assay for celiac disease.

AIM: To determine the diagnostic accuracy of a new point-of-care assay detecting anti-deamidated gliadin peptides in celiac disease (CD) patients. METHODS: One-hundred-and-twelve patients (age range: 1.8-79.2 years old) with clinical symptoms suggestive of CD and/or first-degree relatives (FDR) of CD patients (n = 66), and confirmed CD on a gluten-free diet (GFD) (n = 46), were prospectively enrolled in the study at Gastroenterology outpatient clinics for adult patients and from the Gastroenterology Consultation Ward at the Pediatric Department of the University Hospital of Geneva. Written informed consent was obtained from all subjects enrolled. The study received approval from the local ethics committee. The original CD diagnosis had been based on serum-positive IgA anti-tissue transglutaminase enzyme-linked immunosorbent assay (ELISA) (QuantaLite™, Inova Diagnostics, San Diego, CA, United States) and on biopsy results. Serum samples from all study participants were tested by the new CD lateral flow immunochromatographic assay (CD-LFIA) device, Simtomax® Blood Drop (Augurix SA, BioArk, Monthey, Switzerland) to detect immunoglobulin (Ig)A and IgG antibodies against deamidated gliadin peptides. The diagnostic performance was evaluated using receiver operating characteristic curves with 95%CIs. A cut-off of 2 on the Rann colorimetric scale was used to calculate the device's sensitivity and specificity. RESULTS: CD-LFIA was highly accurate in detecting untreated celiac patients. In the group of patients with CD symptoms and/or FDR, eight new cases of CD were detected by ELISA and biopsy. All of these new cases were also correctly identified by CD-LFIA. The test yielded four false positive and four false negative results. The false positive results were all within the groups with clinical symptoms suggestive of CD and/or FDR, whereas the false negative results were all within the GFD group. The test yeld a sensitivity of 78.9% (95%CI: 54.4-93.9) and specificity of 95.7% (95%CI: 89.4-98.8), and the area under the curve reached 0.893 (95%CI: 0.798-0.988). The Kappa coefficient, calculated according to the values obtained by two readers from the same device, was of 0.96 (SE: 0.06). When the GFD patients were excluded from the analysis, the area under the curve reached 0.989 (95%CI: 0.971-1.000) and the Kappa coefficient, calculated according to the values obtained by two readers from the same device, became 0.96 (SE: 0.07). Furthermore, using the Rann scale cut-off of 2 without the GFD patients, sensitivity was 100% and specificity was 93.1% (95%CI: 83.3-98.1). CONCLUSION: The new CD-LFIA rapid screening test shows good diagnostic accuracy, sensitivity and specificity, and may rule out CD in patients with CD-related symptoms.

Evaluation of a point-of-care test based on deamidated gliadin peptides for celiac disease screening in a large pediatric population.

OBJECTIVES: Celiac disease (CD) is nowadays known to be a common chronic enteropathy that is becoming a growing public health concern. Yet, it is estimated that more than 90% of patients remain undiagnosed. A point-of-care diagnostic test can be a rapid and cost-effective solution in the first-line screening of CD. The aim of this study is to evaluate the performance of a novel point-of-care screening test in a large pediatric population. MATERIALS AND METHODS: Serum samples were collected from a cohort of 250 children presenting either an increased risk or a clinical suspicion of CD. All sera were tested using the point-of-care test detecting IgA and IgG antibodies against a combination of three different deamidated gliadin peptides as well as total IgA. The results of the screening test were compared with an enzyme-linked tissue transglutaminase immunosorbent assay and with histology resulting from intestinal biopsies performed in patients with elevated titers of antitissue transglutaminase antibodies. RESULTS: The point-of-care test showed highly concordant results with the laboratory immunoassay, yielding a sensitivity of 93.1 (78-98.1%) and a specificity of 95% (91.2-97.2%), with a diagnostic accuracy of 94.8% (91.3-96.9%) and a negative predictive value of 99.1% (96.6-99.7%). The screening test identified all patients with celiac-type histology findings on biopsy, as well as all patients with concomitant IgA deficiency. CONCLUSION: With a high diagnostic accuracy, this novel point-of-care approach is an efficient tool for CD case finding in pediatric populations. It has the potential to improve the management of celiac patients in primary care by providing faster counseling and treatment.