Monitoraggio dei marcatori sierologici di celiachia dopo l’avvio di dieta aglutinata: studio multicentrico pediatrico

ABSTRACT INTRODUCTION. The gluten-free diet (GFD) leads to a progressive reduction in the serum levels of anti-transglutaminase IgA antibodies (anti-TTG), which are routinely monitored to assess the regression of celiac enteropathy and the adherence to the GFD. However, to date, the time required for anti-TTG normalization in children affected by celiac disease has not been clearly defined, nor it has been determined whether this timing varies based on patient characteristics. AIMS OF THE STUDY. 1. To determine the time required to achieve anti-TTG normalization after initiating a GFD in a cohort of children with celiac disease. 2. To assess the impact of diagnostic variables on the rate of anti-TTG normalization, including initial anti-TTG levels, sex, age, clinical presentation, and histological disease severity. 3. To evaluate the influence of the analytical method used for anti-TTG measurement on antibody normalization rate. METHODS. A retrospective bicentric study was conducted including all patients under 18 years of age diagnosed with celiac disease at the University Hospital of Padova between January 2010 and July 2022, and at the San Bonifacio Hospital from January 2012 to September 2024. Patients with confirmed or suspected non-adherence to the GFD, as well as those with IgA deficiency, were excluded from the analysis. For each patient, demographic, clinical, histological, and serological longitudinal data (i.e., anti-TTG levels at diagnosis and at 0.5, 1, 2, 3, and 5 years post-diagnosis), were systematically collected. To allow comparison between data obtained with different laboratory methods, anti-TTG levels were expressed as multiples of the upper limit of normal (x ULN). Statistical analysis was performed using R 4.2 software. RESULTS. The study involved 406 children (256 females and 150 males) diagnosed with celiac disease at a median age of 7 years and with a median follow-up duration of 737 days (range 16-4458). At presentation, 79.3% of patients exhibited symptoms of celiac disease, with the most prevalent being abdominal pain, growth failure, and diarrhea. The median anti-TTG level at diagnosis was 18.2 the upper limit of normal (x ULN), ranging from 5.7 to 69.8 x ULN. The median time for anti-TTG normalization was 14.7 months (range 9.5-24.3). The proportion of children with negative anti-TTG at 1, 2, 3, and 5 years from diagnosis was 39%, 74%, 92%, and 99%, respectively. Anti-TTG levels at diagnosis >10 x ULN and female gender were associated with a slower rate of antibody normalization. In contrast, age at diagnosis, presence of symptoms, severity of histological lesions and the analytical method used for anti-TTG assessment (CLIA vs. FEIA) did not predict the rate of anti-TTG normalization over time. CONCLUSIONS. Anti-TTG antibodies exhibit a progressive reduction after starting the GFD, with normalization occurring within 14 months after celiac disease diagnosis in the 50% of children. Patients with higher levels of anti-TTG at diagnosis experience a slower normalization rate. In terms of sample size, our study ranks as the third-largest investigation into the timing of anti-TTG normalization among children with celiac disease. Further research is warranted to validate these findings and to establish individualized reference values, thereby supporting personalized monitoring approaches.