Fluctuating Transglutaminase Autoantibodies Are Related to Histologic Features of Celiac Disease

Background & Aims: Asymptomatic children at risk for celiac disease (CD) and seropositive for immunoglobulin A anti-TG autoantibodies (TGAA) may lack small intestinal mucosal changes characteristic of CD. We have followed a group of children with serial testing for TGAA. Methods: Subjects were a group of at-risk children comprised of infants expressing HLA-DR3 on newborn screening, those with type 1A diabetes, or a first-degree relative of someone with type 1 diabetes. All children participating in the prospective study for development of CD underwent serial testing for TGAA. Data from clinical evaluation and small intestinal biopsy were compared to the TGAA levels followed over time. Results: In 42 children, serial TGAA determinations while on a glutencontaining diet showed levels fluctuating 10-100-fold over 3-12 months. A TGAA index more than 0.5 had a positive predictive value (PPV) for histologic confirmation of CD of 96% (22/23). A TGAA index above the usual cutoff for positivity (0.05) had a PPV of only 76% (28/37). Conclusions: In children with TGAA seropositivity, the TGAA level varied over time and a higher titer predicted an abnormal biopsy characteristic of CD. A threshold for biopsy for diagnosis of CD could be set higher for screening-identified cases than for clinically identified cases to decrease the frequency of performing normal biopsies.