Exploring Total Immunoglobulin A's Impact on Non-Biopsy Diagnosis of Celiac Disease: Implications for Diagnostic Accuracy

Abstract

Objective: In the current debate surrounding the biopsy-free diagnosis of CeD, it is crucial to identify factors influencing the accuracy of results. This study investigated the impact of total IgA on the non-invasive diagnosis of celiac disease (CeD).

Methods: We retrospectively assessed total IgA titers' influence on the diagnostic accuracy of different tTG-IgA thresholds compared to the upper reference value (UNL).

Results: Of 165 included patients, tTG-IgA values at 10× UNL and 6× UNL showed specificity of 82.6% and 73.9% and sensitivity of 49.3% and 69.0%, respectively, in predicting intestinal villous atrophy (Marsh 3). In 130 patients, total IgA levels were known at baseline. These patients were divided into three tertiles according to total IgA, i.e., patients with lower, intermediate, or higher total IgA within the population. For patients with total IgA ≥ 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL resulted in decreased specificity from 71.4% to 42.8% and increased sensitivity from 67.6% to 81.1%. For patients with total IgA < 174 mg/dL and between 174 mg/dL and 245 mg/dL, using a tTG-IgA cutoff of 6× UNL instead of 10× UNL maintained specificity (75.0% and 85.7%, respectively) with increased sensitivity (from 46.2% to 64.1% and from 36.1% to 52.8%, respectively).

Conclusions: In conclusion, total IgA influences the diagnostic accuracy of a predetermined tTG-IgA cutoff. Greater consideration should be given to total IgA, beyond its deficiency, in evaluating the applicability and accuracy of non-invasive CeD diagnosis.

Keywords: celiac disease; diagnostic accuracy; intestinal villous atrophy; non-biopsy diagnosis; tissue transglutaminase antibodies; total IgA.

Figure 1

Receiver operating characteristic curve (ROC) analysis of tTG-IgA values against Marsh 3 histology. Diagonal dotted line represents the reference line (random classifier).

Figure 2

Signal detection plot of the binary classification of patients with and without Marsh 3 histological lesions according to an anti-trasglutaminase IgA antibodies (tTG-IgA) on upper normal level (UNL) rate >10× vs. >6× (dotted vertical lines) in patients with total IgA < 174 mg/dL (I tertile), total IgA ≥ 174 and <245 mg/dL (II tertile), and total IgA ≥ 245 mg/dL (III tertile). The colors shown in the legend may vary from the legend due to them overlapping within the graph.