William Hagopian1, Hye-Seung Lee2, Edwin Liu3, Marian Rewers3, Jin-Xiong She4, Anette-G Ziegler5, Åke Lernmark6, Jorma Toppari7, Stephen S Rich8, Jeffrey P Krischer2, Henry Erlich9, Beena Akolkar10, Daniel Agardh6. 1. Diabetes Programs Division, Pacific Northwest Research Institute, Seattle, Washington; wah@uw.edu. 2. Department of Pediatrics, Health Informatics Institute, University of South Florida, Tampa, Florida. 3. Department of Pediatrics, Children's Hospital Colorado, University of Colorado, Aurora, Colorado. 4. Center for Biotechnology and Genomic Medicine, Augusta University, Augusta, Georgia. 5. Institute of Diabetes Research, Helmholtz Zentrum München, Oberschleißheim, Germany. 6. Department of Clinical Sciences, Skåne University Hospital, Lund University, Malmö, Sweden. 7. Department of Pediatrics, Turku University Central Hospital, Turku, Finland. 8. Center for Public Health Genomics, University of Virginia, Charlottesville, Virginia. 9. Children's Hospital of Oakland Research Institute, Oakland, California; and. 10. Diabetes Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland.
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.
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.
Authors: Romain Bouziat; Reinhard Hinterleitner; Judy J Brown; Jennifer E Stencel-Baerenwald; Mine Ikizler; Toufic Mayassi; Marlies Meisel; Sangman M Kim; Valentina Discepolo; Andrea J Pruijssers; Jordan D Ernest; Jason A Iskarpatyoti; Léa M M Costes; Ian Lawrence; Brad A Palanski; Mukund Varma; Matthew A Zurenski; Solomiia Khomandiak; Nicole McAllister; Pavithra Aravamudhan; Karl W Boehme; Fengling Hu; Janneke N Samsom; Hans-Christian Reinecker; Sonia S Kupfer; Stefano Guandalini; Carol E Semrad; Valérie Abadie; Chaitan Khosla; Luis B Barreiro; Ramnik J Xavier; Aylwin Ng; Terence S Dermody; Bana Jabri Journal: Science Date: 2017-04-07 Impact factor: 47.728
Authors: Maria I Vazquez-Roque; Michael Camilleri; Thomas Smyrk; Joseph A Murray; Eric Marietta; Jessica O'Neill; Paula Carlson; Jesse Lamsam; Denise Janzow; Deborah Eckert; Duane Burton; Alan R Zinsmeister Journal: Gastroenterology Date: 2013-01-25 Impact factor: 22.682
Authors: Christopher T Brown; Austin G Davis-Richardson; Adriana Giongo; Kelsey A Gano; David B Crabb; Nabanita Mukherjee; George Casella; Jennifer C Drew; Jorma Ilonen; Mikael Knip; Heikki Hyöty; Riitta Veijola; Tuula Simell; Olli Simell; Josef Neu; Clive H Wasserfall; Desmond Schatz; Mark A Atkinson; Eric W Triplett Journal: PLoS One Date: 2011-10-17 Impact factor: 3.240
Authors: William A Hagopian; Henry Erlich; Ake Lernmark; Marian Rewers; Anette G Ziegler; Olli Simell; Beena Akolkar; Robert Vogt; Alan Blair; Jorma Ilonen; Jeffrey Krischer; JinXiong She Journal: Pediatr Diabetes Date: 2011-05-12 Impact factor: 3.409
Authors: Kaisa M Kemppainen; Alexandria N Ardissone; Austin G Davis-Richardson; Jennie R Fagen; Kelsey A Gano; Luis G León-Novelo; Kendra Vehik; George Casella; Olli Simell; Anette G Ziegler; Marian J Rewers; Åke Lernmark; William Hagopian; Jin-Xiong She; Jeffrey P Krischer; Beena Akolkar; Desmond A Schatz; Mark A Atkinson; Eric W Triplett Journal: Diabetes Care Date: 2014-12-17 Impact factor: 17.152
Authors: Katherine V Williams; Christina L Cristaldi; Rachel G Miller; Vincent C Arena; Ingrid Libman; Yihe Huang; Dorothy J Becker; Trevor J Orchard Journal: J Clin Endocrinol Metab Date: 2018-10-01 Impact factor: 5.958
Authors: Marisa G Stahl; Fran Dong; Molly M Lamb; Kathleen C Waugh; Iman Taki; Ketil Størdal; Lars C Stene; Marian J Rewers; Edwin Liu; Jill M Norris; Karl Mårild Journal: Scand J Gastroenterol Date: 2020-09-17 Impact factor: 2.423
Authors: Carin Andrén Aronsson; Hye-Seung Lee; Elin M Hård Af Segerstad; Ulla Uusitalo; Jimin Yang; Sibylle Koletzko; Edwin Liu; Kalle Kurppa; Polly J Bingley; Jorma Toppari; Anette G Ziegler; Jin-Xiong She; William A Hagopian; Marian Rewers; Beena Akolkar; Jeffrey P Krischer; Suvi M Virtanen; Jill M Norris; Daniel Agardh Journal: JAMA Date: 2019-08-13 Impact factor: 56.272
Authors: Ana M Calderón de la Barca; Reyna S Castillo-Fimbres; María Esther Mejía-León; Luis Quihui-Cota; Adrián Ochoa-Leyva; Sandra V Aguayo-Patrón Journal: Gut Pathog Date: 2020-08-11 Impact factor: 4.181
Authors: Mary Ellen Vajravelu; Ron Keren; David R Weber; Ritu Verma; Diva D De León; Michelle R Denburg Journal: Pediatr Diabetes Date: 2018-10-09 Impact factor: 4.866
Authors: Ashok Sharma; Xiang Liu; David Hadley; William Hagopian; Wei-Min Chen; Suna Onengut-Gumuscu; Carina Törn; Andrea K Steck; Brigitte I Frohnert; Marian Rewers; Anette-G Ziegler; Åke Lernmark; Jorma Toppari; Jeffrey P Krischer; Beena Akolkar; Stephen S Rich; Jin-Xiong She Journal: J Autoimmun Date: 2018-01-05 Impact factor: 14.511