Immunologic research · 2026
One threshold does not fit all: assay-specific validation of anti-tTG IgA tests for biopsy-free diagnosis of pediatric celiac disease.
СтатьяВалидационное исследованиеНазвание и аннотация: Перевод пока не подготовлен
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Barrale Maria, Fregapane Maria, Cantisano Vincenzo, Motisi Valeria, Villalta Danilo, Bizzaro Nicola, Brusca Ignazio
Аннотация
BACKGROUND: The ESPGHAN biopsy-free diagnostic algorithm for pediatric celiac disease (CeD) requires serum IgA anti-tissue transglutaminase antibody (anti-tTG IgA) concentrations ≥10 times the upper limit of normal (ULN) in the first blood sample, together with positive IgA endomysial antibodies (EMA) in a second blood sample. However, the transferability of the 10×ULN anti-tTG IgA threshold across different analytical platforms remains uncertain owing to the lack of assay harmonization.
METHODS: Eighty-four children (6-10 years) who underwent duodenal biopsy during the diagnostic work-up for suspected CeD were retrospectively evaluated. Histology was classified according to the Marsh-Oberhuber criteria (65 Marsh-Oberhuber 3, 12 Marsh-Oberhuber 2, and 7 Marsh-Oberhuber 1). Anti-tTG IgA antibodies were measured using one FEIA assay (EliA Celikey IgA) and two CLIA platforms (QUANTA Flash® and Maglumi®). EMA were assessed by indirect immunofluorescence on distal monkey esophagus. ROC analysis evaluated discrimination of mucosal atrophy (Marsh-Oberhuber 3) from non-atrophic lesions (Marsh-Oberhuber 1-2).
RESULTS: Anti-tTG IgA concentrations correlated significantly with histological severity for all assays (Spearman's ρ=0.670-0.736; p<0.0001). AUCs ranged from 0.961 to 0.992. At 10×ULN, QUANTA Flash® showed 100% sensitivity and 47.4% specificity, whereas Maglumi® and EliA Celikey IgA showed 100% specificity with sensitivities of 70.8% and 86.2%, respectively. For QUANTA Flash®, 42×ULN was required to achieve 100% specificity. In analyses targeting PPV ≥95%, the corresponding thresholds were 7.54×ULN for Maglumi®, 28.55×ULN for QUANTA Flash®, and 6.10×ULN for EliA Celikey IgA.
CONCLUSIONS: In this selected anti-tTG IgA-positive cohort, the quantitative relationship between anti-tTG IgA and mucosal atrophy differed across automated assays. Expression of results as multiples of the ULN did not fully compensate for inter-assay analytical variability. These findings support assay-specific verification of decision limits, but the retrospective design and selection based on QUANTA Flash positivity limit generalization of the diagnostic performance estimates to unselected children undergoing evaluation for CeD.
METHODS: Eighty-four children (6-10 years) who underwent duodenal biopsy during the diagnostic work-up for suspected CeD were retrospectively evaluated. Histology was classified according to the Marsh-Oberhuber criteria (65 Marsh-Oberhuber 3, 12 Marsh-Oberhuber 2, and 7 Marsh-Oberhuber 1). Anti-tTG IgA antibodies were measured using one FEIA assay (EliA Celikey IgA) and two CLIA platforms (QUANTA Flash® and Maglumi®). EMA were assessed by indirect immunofluorescence on distal monkey esophagus. ROC analysis evaluated discrimination of mucosal atrophy (Marsh-Oberhuber 3) from non-atrophic lesions (Marsh-Oberhuber 1-2).
RESULTS: Anti-tTG IgA concentrations correlated significantly with histological severity for all assays (Spearman's ρ=0.670-0.736; p<0.0001). AUCs ranged from 0.961 to 0.992. At 10×ULN, QUANTA Flash® showed 100% sensitivity and 47.4% specificity, whereas Maglumi® and EliA Celikey IgA showed 100% specificity with sensitivities of 70.8% and 86.2%, respectively. For QUANTA Flash®, 42×ULN was required to achieve 100% specificity. In analyses targeting PPV ≥95%, the corresponding thresholds were 7.54×ULN for Maglumi®, 28.55×ULN for QUANTA Flash®, and 6.10×ULN for EliA Celikey IgA.
CONCLUSIONS: In this selected anti-tTG IgA-positive cohort, the quantitative relationship between anti-tTG IgA and mucosal atrophy differed across automated assays. Expression of results as multiples of the ULN did not fully compensate for inter-assay analytical variability. These findings support assay-specific verification of decision limits, but the retrospective design and selection based on QUANTA Flash positivity limit generalization of the diagnostic performance estimates to unselected children undergoing evaluation for CeD.