Diagnostic value of persistently low positive TGA-IgA titers in symptomatic chIldren with suspected celiac disease

Objectives: While the algorithm to diagnose celiac disease (CD) in children with elevated anti-transglutaminase IgA (TGA-IgA) titers (> 10 times upper limit of normal, ULN) is well defined, the management of children with low TGA-IgA values represents a clinical challenge. We aimed to identify the diagnostic value of persistently low positive TGA-IgA titers in predicting CD in children. Methods: We retrospectively analyzed children with symptoms or signs of CD, not eligible for a no-biopsy approach. We included children with at least two TGA-IgA measurements, EMA assessment and esophagogastroduodenoscopy (EGD) with biopsies. TGA-IgA values were provided as multiples of upper limit normal (ULN). Patients were classified in groups according to median TGA-IgA values: A (TGA-IgA>1 ≤ 5 x ULN; defined as “low-positive”), B (TGA-IgA > 5 < 10 x ULN; “moderate-positive”) and C (controls). Results: Data of 281 children were analyzed. Of 162 children in Group A, CD was diagnosed in 142 (87.7%), while normal duodenal mucosa was found in 20. In Group B, all 62 children (100%) received a CD diagnosis. Group C included 57 controls. EMA were undetectable in 31 (15%) of mucosal atrophy cases. On the ROC curve (AUC = 0.910), a mean value of 1.7 ULN showed a sensitivity of 81.4% and specificity of 81.8% to predict mucosal damage. Conclusions: Repeated low or moderate TGA-IgA values (< 5 ULN or <10 ULN) are good predictors of a CD diagnosis. Symptomatic children with persistently low positive TGA-IgA titers should undergo EGD regardless of their EMA statu