Effect of Abatacept on T cell autoreactivity in Type 1 Diabetes

• Research type

  Research Study

• Full title

  The Effect of Co-Stimulation Blockade on T Cell Auto-Reactivity in New Onset Type 1 Diabetes: COMBAT Type 1

• IRAS ID

  214837

• Contact name

  Mark Peakman

• Contact email

  mark.peakman@kcl.ac.uk

• Sponsor organisation

  Kings College London

• Duration of Study in the UK

  1 years, 11 months, 30 days

• Research summary

  Research Summary

  The study is designed to investigate the mechanism of action of Abatacept in type 1 diabetes.
  Type 1 diabetes results from the destruction of beta cells in the pancreas (the cells which are responsible for making insulin) by the body's own adaptive immune system. A key stage in the destruction of these cells is the activation of T cells (a type of white blood cell). T cells are activated by binding to antigen presenting cells (APC); this requires binding of the antigen presented by the APC to the T cell receptor, and additional binding between surface molecules on both cells. The latter is referred to as co-stimulation. Abatacept blocks this process of co-stimulation by binding preferentially to the proteins on the APC surface, thus preventing binding to the T cell.

  Abatacept has been shown to be effective in halting the process of beta cell destruction, however the exact mechanism of action is not known. In particular, the effect of Abatacept on T cells which specifically target beta cells has not been studied.
  This study aims to identify this mechanism of action by analysing the immune cells of patients with recent onset type 1 diabetes before, during and after treatment with Abatacept.

  Summary of Results

  The COMBAT Study replicated previously-observed changes in subsets immune cells in patients with newly diagnosed type 1 diabetes after treatment with Abatacept, and extended these findings by identifying novel changes in subsets of these cells. This furthers our understanding of the mechanism of action of Abatacept in the treatment of new-onset type 1 diabetes, and more generally our understanding of the underlying immune process in this disease.
  We also identifed a particular pattern of immune cells which predicted how effective Abatacept would be in halting the progression of type 1 diabetes.

• REC name

  London - Fulham Research Ethics Committee

• REC reference

  17/LO/0928

• Date of REC Opinion

  6 Jul 2017

• REC opinion

  Further Information Favourable Opinion