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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. LU ; Lernmark, Åke LU ; Toppari, Jorma; Rich, Stephen S. and Krischer, Jeffrey P., et al. (2017) In Pediatrics 140(5).
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... (More)

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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published
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Pediatrics
volume
140
issue
5
publisher
American Academy of Pediatrics
external identifiers
  • scopus:85033597277
ISSN
1098-4275
DOI
10.1542/peds.2017-1305
language
English
LU publication?
yes
id
7f951809-d3e1-4d63-820e-eb37ea646d63
date added to LUP
2017-11-22 13:56:50
date last changed
2018-07-08 04:28:26
@article{7f951809-d3e1-4d63-820e-eb37ea646d63,
  abstract     = {<p>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.</p><p>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.</p><p>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.</p><p>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.</p>},
  articleno    = {e20171305},
  author       = {Hagopian, William and Lee, Hye Seung and Liu, Edwin and Rewers, Marian and She, Jin Xiong and Ziegler, Anette G. and Lernmark, Åke and Toppari, Jorma and Rich, Stephen S. and Krischer, Jeffrey P. and Erlich, Henry and Akolkar, Beena and Agardh, Daniel and , },
  issn         = {1098-4275},
  language     = {eng},
  month        = {11},
  number       = {5},
  publisher    = {American Academy of Pediatrics},
  series       = {Pediatrics},
  title        = {Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity},
  url          = {http://dx.doi.org/10.1542/peds.2017-1305},
  volume       = {140},
  year         = {2017},
}