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Innate immune activity as a predictor of persistent insulin secretion and association with responsiveness to CTLA4-Ig treatment in recent-onset type 1 diabetes – published online 30/08/2018

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Susanne M. Cabrera, Samuel Engle, Mary Kaldunski, Shuang Jia, Rhonda Geoffrey, Pippa Simpson, Aniko Szabo, Cate Speake, Carla J. Greenbaum, Type 1 Diabetes TrialNet CTLA4-Ig (Abatacept) Study Group, Yi-Guang Chen, Martin J. Hessner

Recent studies have drawn attention to the phenotypic heterogeneity that exists among individuals with type 1 diabetes. In trials of disease-modifying immunotherapy conducted at clinical onset, heterogeneity in the rate of disease progression poses challenges in detecting the effect of treatment on preservation of stimulated C-peptide. In this issue, Cabrera et al ( investigated whether discrete subtypes of type 1 diabetes exist, based on immunoregulatory profiles at clinical onset. They report that levels of innate inflammation at clinical onset were very heterogeneous among newly diagnosed individuals. Importantly, the post-onset duration of persistent insulin secretion was negatively related to baseline inflammation and positively associated with baseline abundance of circulating activated regulatory T cells. Furthermore, in an ancillary analysis of TrialNet CTLA4-Ig trial (TN-09) participants, the therapeutic response to CTLA4-Ig was associated with higher levels of baseline inflammation. These findings suggest that measures that predict the post-onset disease course and the response to therapeutic intervention could enable individual stratification that will lead to the development of individualised therapies.

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