Treatment with ustekinumab alters circulating immune cells in a dose-dependent manner in type 1 diabetes

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Abstract Summary

Type 1 diabetes (T1D) is a chronic disease that usually presents at childhood and affects millions of individuals worldwide. T1D is caused by T cell-mediated destruction of pancreatic beta cells, leaving affected individuals reliant on life-long exogenous insulin. It is likely that blockade of pathogenic T cells in individuals with recent-onset T1D will halt the autoimmune destruction of beta cells and allow restoration of endogenous insulin secretion. Ustekinumab is an antibody that inhibits IL-17 and IFN-γ signalling in T cells, both of which have been implicated in the pathogenesis of T1D. Ustekinumab has been effectively used to treat psoriasis but it is currently unclear if it will improve outcomes in people with T1D.

In 2016-2017, a phase IIa trial was undertaken to test the efficacy of ustekinumab administration to 20 young adults (18-25yrs) with recent-onset T1D. Patients were randomised to 90mg and 45mg treatment groups. Blood was taken at baseline and at 4, 28 and 52 weeks post-ustekinumab treatment. Flow cytometry was used to measure immune cell populations before and after treatment to determine the effect of ustekinumab on circulating immune cells. 

There was an increase in the ratio of B cells to T cells after treatment with ustekinumab, compared to baseline. In addition to a reduction in the production of IL-17.1 (IL-17+ and IFN-γ+ T cells), there were changes in other immune populations including dendritic cells, T cells, and B cells in the 90mg compared to the 45mg treatment groups.

These results indicate the ustekinumab may alter immune cell populations in a dose-dependent manner in people with T1D. Changes in immune cell populations may predict response to ustekinumab therapy. Two larger clinical trials have recently been approved in Canada and the United Kingdom. These trials will be harmonized to determine if changes in immune biomarkers are association with a clinical response to ustekinumab treatment.

Submission ID :
IDS9685
Submission Type
Abstract Topics
Department of Surgery, The University of British Columbia, and Child & Family Research Institute, Vancouver, Canada.
University of Toronto
Department of Surgery, The University of British Columbia, and Child & Family Research Institute, Vancouver, Canada.
Department of Surgery, The University of British Columbia, and Child & Family Research Institute, Vancouver, Canada.
Department of Surgery, The University of British Columbia, and Child & Family Research Institute, Vancouver, Canada.
Department of Endocrinology, University of British Columbia, Vancouver, Canada., & BC Diabetes, Vancouver, Canada.
University of British Columbia
University of British Columbia

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Event dates:
Thursday 25 October - Monday 29 October 2018

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Monday 14 May 2018

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July 2018

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