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

Abstract

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.

Keywords: Celiac disease; Deamidated gliadin; Point-of-care assay; Screening; Total immunoglobulin A.

Figure 1

Celiac disease lateral-flow immunochromatographic assay visual result interpretation. CT: Control line; A: Position for detection of IgA and IgG anti-DGP; B: Position for detection of total IgA; CD: Celiac disease; IgA: Immunoglobulin A.

Figure 2

Histogram showing the immunoglobulin A-tissue transglutaminase enzyme-linked immunosorbent assay and celiac disease lateral-flow immunochromatographic assay test results. Text in gray indicates false-positive and false-negative results by celiac disease lateral-flow immunochromatographic assay (CD-LFIA). FDR: First-degree relatives; GFD: Gluten-free diet; Control: First-degree relatives and patients with celiac disease symptoms diagnosed as celiac disease (CD)-negative; IgA-tTG: Immunoglobulin A-tissue transglutaminase.

Figure 3

Diagnostic performance of the celiac disease lateral-flow immunochromatographic assay test determined by receiver operating characteristic curve analysis. A: GFD, FDR and CD symptoms; B: FDR and CD symptoms. FDR: First-degree relatives; CD: Celiac disease symptoms; GFD: Gluten-free diet; ROC: Receiver operating characteristic.