Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity

Research output: Contribution to journalArticle

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.

Details

Authors
  • William Hagopian
  • Hye Seung Lee
  • Edwin Liu
  • Marian Rewers
  • Jin Xiong She
  • Anette G. Ziegler
  • Åke Lernmark
  • Jorma Toppari
  • Stephen S. Rich
  • Jeffrey P. Krischer
  • Henry Erlich
  • Beena Akolkar
  • Daniel Agardh
  • TEDDY Study Group
Organisations
External organisations
  • University of South Florida
  • University of Colorado
  • Helmholtz Zentrum München
  • Skåne University Hospital
  • Turku University Hospital
  • University of Virginia
  • Pacific Northwest Diabetes Research Institute
  • Augusta University
  • Children's Hospital Oakland Research Institute
  • National Institute of Diabetes and Digestive and Kidney Diseases
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
  • Rheumatology and Autoimmunity
Original languageEnglish
Article numbere20171305
JournalPediatrics
Volume140
Issue number5
Publication statusPublished - 2017 Nov 1
Publication categoryResearch
Peer-reviewedYes