Innate immune activity as a predictor of persistent insulin secretion and association with responsiveness to CTLA4-Ig treatment in recent-onset type 1 diabetes

Diabetologia
Susanne M CabreraM J Hessner

Abstract

The study aimed to determine whether discrete subtypes of type 1 diabetes exist, based on immunoregulatory profiles at clinical onset, as this has significant implications for disease treatment and prevention as well as the design and analysis of clinical trials. Using a plasma-based transcriptional bioassay and a gene-ontology-based scoring algorithm, we examined local participants from the Children's Hospital of Wisconsin and conducted an ancillary analysis of TrialNet CTLA4-Ig trial (TN-09) participants. The inflammatory/regulatory balance measured during the post-onset period was highly variable. Notably, a significant inverse relationship was identified between baseline innate inflammatory activity and stimulated C-peptide AUC measured at 3, 6, 12, 18 and 24 months post onset among placebo-treated individuals (p ≤ 0.015). Further, duration of persistent insulin secretion was negatively related to baseline inflammation (p ≤ 0.012) and positively associated with baseline abundance of circulating activated regulatory T cells (CD4+/CD45RA-/FOXP3high; p = 0.016). Based on these findings, data from participants treated with CTLA4-Ig were stratified by inflammatory activity at onset; in this way, we identified pathways and transc...Continue Reading

References

Sep 30, 1993·The New England Journal of Medicine·UNKNOWN Diabetes Control and Complications Trial Research GroupC Siebert
Nov 24, 1999·The Journal of Clinical Investigation·M PeakmanR M Chicz
Feb 12, 2002·Bioinformatics·Alexander SturnZlatko Trajanoski
Feb 3, 2004·The Journal of Clinical Investigation·Sefina ArifMark Peakman
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Nov 23, 2005·Pediatric Clinics of North America·Michael J HallerDesmond Schatz
Aug 16, 2006·Clinical and Experimental Immunology·B Z AlizadehUNKNOWN DIABMARKER Study Group
Jan 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Xujing WangMartin J Hessner
Feb 29, 2008·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Srinath SandaMatthias von Herrath
Sep 23, 2008·Diabetes Research and Clinical Practice·M ThunanderM Landin-Olsson
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
May 14, 2009·Diabetes Care·Henrik B MortensenUNKNOWN Hvidoere Study Group on Childhood Diabetes
Jun 20, 2013·JAMA : the Journal of the American Medical Association·Anette G ZieglerGeorge S Eisenbarth
Aug 3, 2013·Pharmacological Reviews·Francisco J Quintana, David H Sherr
Aug 21, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christine M DeppongJonathan M Green
Apr 25, 2014·Diabetes·Yi-Guang ChenMartin J Hessner
Aug 19, 2014·Nature Reviews. Drug Discovery·Katrina J Falkenberg, Ricky W Johnstone
Dec 19, 2014·Diabetes Care·Asa K DavisUNKNOWN T1D Exchange Clinic Network
Jan 13, 2015·Molecular Aspects of Medicine·Michael P MorranMassimo Pietropaolo
May 20, 2015·Translational Research : the Journal of Laboratory and Clinical Medicine·Susanne M CabreraMartin J Hessner
Dec 25, 2015·Diabetologia·Susanne M CabreraMartin J Hessner
Apr 27, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Rosita MoyaJoanna Davida Davies
Jun 16, 2016·Lancet·Flemming Pociot, Åke Lernmark
Jun 16, 2016·Lancet·Marian Rewers, Johnny Ludvigsson

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Citations

Mar 5, 2019·JCI Insight·Peter S LinsleyMatthew J Dufort
Feb 8, 2020·Expert Opinion on Investigational Drugs·Ousama RachidYousef Haik
Jun 17, 2020·The Journal of Clinical Endocrinology and Metabolism·Martin J Hessner, Susanne M Cabrera
Oct 26, 2018·Frontiers in Medicine·Ken Coppieters, Matthias von Herrath
Jul 8, 2019·Journal of Pediatric Endocrinology & Metabolism : JPEM·Madalena Sales LuisCatarina Limbert
Dec 11, 2020·JCI Insight·Aditi NarsaleJoanna D Davies
Mar 18, 2021·Reviews in Endocrine & Metabolic Disorders·Natalia G VallianouMaria Dalamaga
Mar 21, 2021·Diabetes·Peter S LinsleyGerald T Nepom

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Methods Mentioned

BETA
flow cytometry

Clinical Trials Mentioned

NCT00505375

Software Mentioned

Partek Genomics Suite
Ingenuity Pathway Analysis ( IPA
WGCNA
Bioconductor
IPA

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