A type I interferon transcriptional signature precedes autoimmunity in children genetically at risk for type 1 diabetes

Diabetes
Ricardo C FerreiraAnette-G Ziegler

Abstract

Diagnosis of the autoimmune disease type 1 diabetes (T1D) is preceded by the appearance of circulating autoantibodies to pancreatic islets. However, almost nothing is known about events leading to this islet autoimmunity. Previous epidemiological and genetic data have associated viral infections and antiviral type I interferon (IFN) immune response genes with T1D. Here, we first used DNA microarray analysis to identify IFN-β-inducible genes in vitro and then used this set of genes to define an IFN-inducible transcriptional signature in peripheral blood mononuclear cells from a group of active systemic lupus erythematosus patients (n = 25). Using this predefined set of 225 IFN signature genes, we investigated the expression of the signature in cohorts of healthy controls (n = 87), patients with T1D (n = 64), and a large longitudinal birth cohort of children genetically predisposed to T1D (n = 109; 454 microarrayed samples). Expression of the IFN signature was increased in genetically predisposed children before the development of autoantibodies (P = 0.0012) but not in patients with established T1D. Upregulation of IFN-inducible genes was transient, temporally associated with a recent history of upper respiratory tract infections...Continue Reading

References

Nov 1, 1982·Arthritis and Rheumatism·E M TanR J Winchester
Feb 27, 2003·Proceedings of the National Academy of Sciences of the United States of America·Emily C BaechlerTimothy W Behrens
Mar 19, 2003·The Journal of Experimental Medicine·Lynda BennettVirginia Pascual
Sep 23, 2003·Nature Immunology·Agnes Le BonDavid F Tough
Aug 20, 2005·Nature Reviews. Immunology·Thomas DeckerSilvia Stockinger
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Agnes Le BonDavid F Tough
Feb 24, 2006·The Journal of Experimental Medicine·Marc EhlersJeffrey V Ravetch
May 2, 2006·Statistical Applications in Genetics and Molecular Biology·Gordon K Smyth
Jun 28, 2007·The Journal of Clinical Endocrinology and Metabolism·Ellen C KaizerPerrin C White
Nov 6, 2007·Nature Reviews. Immunology·Matthias von HerrathKevan Herold
Aug 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Qing LiHugh O McDevitt
May 12, 2009·Nature Genetics·Jeffrey C BarrettUNKNOWN Type 1 Diabetes Genetics Consortium
Jul 29, 2010·Current Diabetes Reports·Francesco DottaFrancesco Vendrame
Sep 15, 2010·The Journal of Experimental Medicine·Giorgio Trinchieri
Sep 17, 2010·PloS One·Kate DownesJohn A Todd
Feb 15, 2011·Arthritis Research & Therapy·Mary K Crow
Jul 22, 2011·Diabetes Care·Kan NakamuraUNKNOWN Research Committee on Type 1 Diabetes of the Japan Diabetes Society
Oct 4, 2011·Cell·Herbert W Virgin, John A Todd
Jan 4, 2012·The Journal of Experimental Medicine·Ken T CoppietersMatthias G von Herrath
Jan 10, 2012·Nature Reviews. Immunology·José M González-NavajasEyal Raz
Apr 26, 2012·PLoS Genetics·Barbara E StrangerEmmanouil T Dermitzakis
Aug 29, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sandra Hervas-StubbsIgnacio Melero
Aug 31, 2012·Multiple Sclerosis : Clinical and Laboratory Research·S MalhotraM Comabella
Jun 12, 2013·Human Molecular Genetics·Dorothee NicklesSergio E Baranzini
Jun 20, 2013·JAMA : the Journal of the American Medical Association·Anette G ZieglerGeorge S Eisenbarth
Jul 24, 2013·Cancer Research·Nicole BacherKerstin Steinbrink

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Citations

Sep 2, 2014·Trends in Endocrinology and Metabolism : TEM·Noel G Morgan, Sarah J Richardson
Jan 17, 2015·Diabetes·Pamela J LincezMarc S Horwitz
May 23, 2015·Diabetes Care·Ezio Bonifacio
Mar 26, 2015·Diabetes·Manuela Battaglia, Mark A Atkinson
Nov 14, 2014·Diabetes·Glen R GallagherJennifer P Wang
Dec 25, 2015·Diabetologia·Susanne M CabreraMartin J Hessner
May 20, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Susanne M CabreraMartin J Hessner
Oct 1, 2015·Pediatric Diabetes·Brigitte I Frohnert, Marian J Rewers
Nov 5, 2015·Current Opinion in Immunology·Hiroki Kato, Takashi Fujita
Sep 4, 2015·Scientific Reports·Susan M ClardyRalph Weissleder
Sep 20, 2015·Current Diabetes Reports·Benjamin M LooneyMichael J Clare-Salzler
Mar 30, 2016·Nature Reviews. Endocrinology·Anne Op de Beeck, Decio L Eizirik
May 16, 2015·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Kine EdvardsenEirik Bratland
Jun 30, 2015·Scandinavian Journal of Immunology·M T HeinonenR Lahesmaa
Oct 25, 2014·Diabetes·Ken T Coppieters, Matthias G von Herrath
Jun 19, 2015·Current Opinion in Endocrinology, Diabetes, and Obesity·Peter A Gottlieb
May 13, 2015·Nature Communications·Xaquin Castro DopicoJohn A Todd
Apr 25, 2015·Diabetes·Teresa Rodriguez-Calvo, Matthias G von Herrath
May 22, 2016·Diabetes·Helen E ThomasThomas W H Kay
Nov 22, 2014·Diabetes·Richard David G Leslie, C Bradford
Jan 12, 2016·Proteomics. Clinical Applications·Amanda J EakinDavid S Gibson
Jun 20, 2016·Journal of Autoimmunity·Yamina HamelPeter van Endert
Jul 15, 2016·Pediatric Diabetes·Robert Moulder, Riitta Lahesmaa
Aug 10, 2016·Viral Immunology·Bo NiklassonWilliam Klitz
Mar 24, 2017·International Reviews of Immunology·Daisuke OriTaro Kawai
Feb 2, 2017·Annual Review of Immunology·Romain BanchereauVirginia Pascual
Oct 6, 2017·Protein Engineering, Design & Selection : PEDS·S MierschS S Sidhu
Oct 19, 2017·Antioxidants & Redox Signaling·Ashley R Burg, Hubert M Tse
May 4, 2018·PLoS Biology·Melissa L HarrisWilliam J Pavan
Mar 8, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cindy AudigerSylvie Lesage
Nov 25, 2017·Seminars in Immunopathology·Mikael KnipTaina Härkönen
Nov 22, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ashley R BurgHubert M Tse

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Methods Mentioned

BETA
density gradient centrifugation
flow cytometry

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