Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Interleukin-1 antagonism moderates the inflammatory state associated with Type 1 diabetes during clinical trials conducted at disease onset

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Conditional ligands for Asian HLA variants facilitate the definition of CD8+ T-cell responses in acute and chronic viral diseases

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Identification and characterization of survivin-derived H-2Kb-restricted CTL epitopes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. High levels of neutralizing IL-6 autoantibodies in 0.1% of apparently healthy blood donors

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Risk of COVID-19 in health-care workers in Denmark: an observational cohort study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Effects of Ketone Bodies on Brain Metabolism and Function in Neurodegenerative Diseases

    Publikation: Bidrag til tidsskriftReviewpeer review

  3. Discontinuation of diabetes medication in the 10 years before death: a nationwide register-based study: 21-25 September 2020.

    Publikation: KonferencebidragKonferenceabstrakt til konferenceForskningpeer review

  4. Mannose-Binding Lectin and Risk of Cardiovascular Events and Mortality in Type 2 Diabetes: A Danish Cohort Study

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Bone resorption is unchanged by liraglutide in type 2 diabetes patients: A randomised controlled trial

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Susanne M Cabrera
  • Xujing Wang
  • Yi-Guang Chen
  • Shuang Jia
  • Mary L Kaldunski
  • Carla J Greenbaum
  • Thomas Mandrup-Poulsen
  • Martin J Hessner
  • Type 1 Diabetes TrialNet Canakinumab Study Group
  • Jørgen Rungby
Vis graf over relationer
It was hypothesized that IL-1 antagonism would preserve β-cell function in new onset Type 1 diabetes (T1D). However, the Anti-Interleukin-1 in Diabetes Action (AIDA) and TrialNet Canakinumab (TN-14) trials failed to show efficacy of IL-1 receptor antagonist (IL-1Ra) or canakinumab, as measured by stimulated C-peptide response. Additional measures are needed to define immune state changes associated with therapeutic responses. Here, we studied these trial participants with plasma-induced transcriptional analysis. In blinded analyses, 70.2% of AIDA and 68.9% of TN-14 participants were correctly called to their treatment arm. While the transcriptional signatures from the two trials were distinct, both therapies achieved varying immunomodulation consistent with IL-1 inhibition. On average, IL-1 antagonism resulted in modest normalization relative to healthy controls. At endpoint, signatures were quantified using a gene ontology-based inflammatory index, and an inverse relationship was observed between measured inflammation and stimulated C-peptide response in IL-1Ra- and canakinumab-treated patients. Cytokine neutralization studies showed that IL-1α and IL-1β additively contribute to the T1D inflammatory state. Finally, analyses of baseline signatures were indicative of later therapeutic response. Despite the absence of clinical efficacy by IL-1 antagonist therapy, transcriptional analysis detected immunomodulation and may yield new insight when applied to other clinical trials.
OriginalsprogEngelsk
TidsskriftEuropean Journal of Immunology
Vol/bind46
Udgave nummer4
Sider (fra-til)1030-1046
Antal sider17
ISSN0014-2980
DOI
StatusUdgivet - apr. 2016

ID: 64973841