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Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis – published online 19/12/2018

Fig 2 from Perdigoto paper

Ana Luisa Perdigoto, Paula Preston-Hurlburt, Pamela Clark, S. Alice Long, Peter S. Linsley, Kristina M. Harris, Steven E. Gitelman, Carla J. Greenbaum, Peter A. Gottlieb, William Hagopian, Alyssa Woodwyk, James Dziura, Kevan C. Herold, the Immune Tolerance Network

In the short term, immune therapies for type 1 diabetes, such as Fc receptor (FcR) non-binding anti-CD3 monoclonal antibodies, can preserve C-peptide and improve glycaemic control, but long-term follow-up studies have been limited. In this issue, Perdigoto et al (https://doi.org/10.1007/s00125-018-4786-9) studied the long-term metabolic and immunological impact of anti-CD3 treatment on participants from the Autoimmunity-Blocking Antibody for Tolerance (AbATE) study. AbATE showed that treatment with the FcR non-binding antibody teplizumab improved C-peptide responses for 2 years after diagnosis. After a mean follow-up of 7 years, Perdigoto and colleagues found that participants previously identified as responders at year 1 retained improved C-peptide responses and lasting immunological changes compared with control and drug-treated non-responders. The authors identified features of T cell subsets that predicted maintenance of C-peptide levels at follow-up, namely, a significantly increased frequency of programmed cell death protein 1-positive central memory and anergic CD8+ T cells. This study highlights the long-lasting effects of immune therapy and how these can be predicted from short-term responses. The authors postulate that combination with other immune or metabolic therapies may further enhance the observed effects of anti-CD3 monoclonal antibody treatment. This article is the subject of a commentary by Lucienne Chatenoud.

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