1445-P: Co-occurrence of Islet, Celiac, and Thyroid Autoimmunity in Children Prospectively Followed from Birth in the TEDDY Study
Authors: CLASEN JOANNA L. , LARSSON HELENA E. , JONSDOTTIR BERGLIND , HALLER MICHAEL J. , AGARDH DANIEL , PARIKH HEMANG M. , LYNCH KRISTIAN F. , LERNMARK ÅKE , REWERS MARIAN , MCINDOE RICHARD , TOPPARI JORMA , ZIEGLER ANETTE-GABRIELE , KRISCHER JEFFREY , AKOLKAR BEENA , HAGOPIAN WILLIAM , VEHIK KENDRA , TEDDY STUDY GROUP THE 
Published: June 2024

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 &lt; 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.

Disclosure
J.L. Clasen: None. H.E. Larsson: None. B. Jonsdottir: None. M.J. Haller: Consultant; Sanofi. Advisory Panel; SAB Biotherapeutics, Inc. Consultant; MannKind Corporation. D. Agardh: None. H.M. Parikh: None. K.F. Lynch: None. Å. Lernmark: Advisory Panel; DiaMyd Medical AB, Stockholm, Sweden. M. Rewers: Advisory Panel; Sanofi. Other Relationship; Sanofi. Consultant; Janssen Pharmaceuticals, Inc. Research Support; Juvenile Diabetes Research Foundation (JDRF). Consultant; Provention Bio, Inc. Research Support; Hemsley Charitable Trust, National Institute of Diabetes and Digestive and Kidney Diseases. R. McIndoe: None. J. Toppari: None. A. Ziegler: None. J. Krischer: None. B. Akolkar: None. W. Hagopian: Research Support; Janssen Pharmaceuticals, Inc., Provention Bio, Inc. Consultant; Sanofi-Aventis U.S., Randox R & D. K. Vehik: None.

Funding
NIH NIDDK (U01 DK63829, U01 DK63861, U01 DK63821, U01 DK63865, U01 DK63863, U01 DK63836, U01 DK63790, UC4 DK63829, UC4 DK63861, UC4 DK63821, UC4 DK63865, UC4 DK63863, UC4 DK63836, UC4 DK95300, UC4 DK100238, UC4 DK106955, UC4 DK112243, UC4 DK117483, U01 DK124166, U01 DK128847, and Contract No. HHSN267200700014C)