Parameters associated with the development of autoimmune diseases in pediatric onset celiac disease

Patients with celiac disease (CeD) have an increased risk of developing other autoimmune diseases (ADs); however, risk factors and predictors for ADs remain unclear. The study objective is to assess predictors for development of ADs among pediatric onset CeD patients. The study included pediatric onset CeD patients, evaluated at Emek Medical Center, and followed for at least 2 years from April 2008 to April 2022. Data were collected from medical records and included baseline and follow-up data of demographics, clinical manifestations, laboratory variables, and subsequent development of ADs. Then, 930 children with CeD were included, and 790 fulfilled inclusion criteria. Patients were followed for a median of 4.9 years (range 2-16 years). During follow-up, 45%, 68%, and 80% normalized their tissue transglutaminase (TTG) levels by 6, 12, and 24 months, respectively. Among the entire cohort, 16 patients (2%) developed type 1 diabetes mellitus, 35 (4.4%) developed Hashimoto's thyroiditis, and 11 (1.3%) developed other ADs. Of 510 patients with sustained serological remission, 39 (7.6%) patients developed ADs compared to 23 (11.5%) of patients without sustained serological remission. In multivariate Cox models, shorter time to TTG normalization (hazard ratio (HR) 0.94 CI 95% 0.88-0.99) and sustained TTG levels less than three times the upper limit of normal (HR 0.87 CI 95% 0.72-0.96) were significantly associated with reduced risk of developing ADs. Conclusion: Effective management of celiac disease, including timely TTG normalization and sustained lower TTG levels, may be important for reducing the risk of subsequent development of ADs in pediatric-onset CeD.What is Known:center dot Pediatric patients with celiac disease (CeD) are at an increased risk of developing autoimmune diseases (ADs). Risk factors contributing to the development of ADs in CeD patients are not well established, particularly in the pediatric population.What is new:center dot Timely TTG normalization and sustained low TTG levels (<3 times ULN) during follow-up are associated with a reduced risk of developing additional ADs in pediatric CeD patients.