Co-occurrence of type 1 diabetes and celiac disease autoimmunity

William Hagopian, Hye Seung Lee, Edwin Liu, Marian Rewers, Jin-Xiong She, Anette G. Ziegler, Ake Lernmark, Jorma Toppari, Stephen S. Rich, Jeffrey P. Krischer, Henry Erlich, Beena Akolkar, Daniel Agardh

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Abstract

BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors. METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed. RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15- 1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors. CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.

Original languageEnglish (US)
Article numbere20171305
JournalPediatrics
Volume140
Issue number5
DOIs
StatePublished - Nov 1 2017

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Celiac Disease
Autoimmunity
Type 1 Diabetes Mellitus
Autoantibodies
Genetic Loci
Demography
Parturition
HLA-DR3 Antigen
HLA-DQ Antigens
HLA-DR Antigens
Single Nucleotide Polymorphism
transglutaminase 2
Cohort Studies
Genotype
Confidence Intervals

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Hagopian, W., Lee, H. S., Liu, E., Rewers, M., She, J-X., Ziegler, A. G., ... Agardh, D. (2017). Co-occurrence of type 1 diabetes and celiac disease autoimmunity. Pediatrics, 140(5), [e20171305]. https://doi.org/10.1542/peds.2017-1305

Co-occurrence of type 1 diabetes and celiac disease autoimmunity. / Hagopian, William; Lee, Hye Seung; Liu, Edwin; Rewers, Marian; She, Jin-Xiong; Ziegler, Anette G.; Lernmark, Ake; Toppari, Jorma; Rich, Stephen S.; Krischer, Jeffrey P.; Erlich, Henry; Akolkar, Beena; Agardh, Daniel.

In: Pediatrics, Vol. 140, No. 5, e20171305, 01.11.2017.

Research output: Contribution to journalArticle

Hagopian, W, Lee, HS, Liu, E, Rewers, M, She, J-X, Ziegler, AG, Lernmark, A, Toppari, J, Rich, SS, Krischer, JP, Erlich, H, Akolkar, B & Agardh, D 2017, 'Co-occurrence of type 1 diabetes and celiac disease autoimmunity', Pediatrics, vol. 140, no. 5, e20171305. https://doi.org/10.1542/peds.2017-1305
Hagopian W, Lee HS, Liu E, Rewers M, She J-X, Ziegler AG et al. Co-occurrence of type 1 diabetes and celiac disease autoimmunity. Pediatrics. 2017 Nov 1;140(5). e20171305. https://doi.org/10.1542/peds.2017-1305
Hagopian, William ; Lee, Hye Seung ; Liu, Edwin ; Rewers, Marian ; She, Jin-Xiong ; Ziegler, Anette G. ; Lernmark, Ake ; Toppari, Jorma ; Rich, Stephen S. ; Krischer, Jeffrey P. ; Erlich, Henry ; Akolkar, Beena ; Agardh, Daniel. / Co-occurrence of type 1 diabetes and celiac disease autoimmunity. In: Pediatrics. 2017 ; Vol. 140, No. 5.
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abstract = "BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors. METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed. RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95{\%} confidence interval [CI]: 1.15- 1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors. CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.",
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AU - Ziegler, Anette G.

AU - Lernmark, Ake

AU - Toppari, Jorma

AU - Rich, Stephen S.

AU - Krischer, Jeffrey P.

AU - Erlich, Henry

AU - Akolkar, Beena

AU - Agardh, Daniel

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