1445-P: Co-occurrence of Islet, Celiac, and Thyroid Autoimmunity in Children Prospectively Followed from Birth in the TEDDY Study

Islet autoantibodies (IA) that precede type 1 diabetes, tissue transglutaminase autoantibodies (tTGA) preceding celiac disease, and thyroid peroxidase (TPOA) or thyroglobulin (ThGA) autoantibodies preceding autoimmune thyroid disease may coincide. We aim to describe the order of first appearance of IA, tTGA, or thyroid autoimmunity in children, as well as the role of thyroid autoimmunity in risk of subsequent development of IA or tTGA. Children (n = 5437) with a genetically determined high risk for autoimmune disease from the USA, Finland, Germany, and Sweden were followed from birth to age 14 or type 1 diabetes diagnosis. Cox regression was used for survival analyses. IA, tTGA, and thyroid autoimmunity were the first or only type of autoantibody to develop in 10%, 20%, and 8% of the children, respectively, and 61% remained autoantibody negative (median follow-up 12.0 years). Among autoantibody positive children, a family history of autoimmune thyroid disease was associated with an increased risk of ThGA (OR 2.05, 95% CI 1.48, 2.85, p < 0.001), but not TPOA (OR 1.18, 95% CI 0.71, 1.95, p = 0.53), as the first or only autoantibody. TPOA as the first or only thyroid autoantibody was associated with increased risk of subsequent development of IA (HR 1.94, 95% CI 1.11, 3.41, p = 0.021) and tTGA (HR 1.69, 95% CI 1.04, 2.75, p = 0.036), while there was no association for ThGA-first thyroid autoimmunity with either IA or tTGA. Among children with IA, thyroid autoimmunity status at the time of IA seroconversion was not associated with risk of IAA versus GADA as the first appearing IA (TPOA-first p = 0.73, ThGA-first p = 0.20). The association between thyroid autoimmunity and either IA or tTGA depends on which thyroid autoantibody appears first. A better understanding of the co-occurrence and order of appearance of these three types of autoantibodies may aid in designing a more personalized approach to identifying individuals at highest risk for autoimmune comorbidity.