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A composite immune signature parallels disease progression across T1D subjects

Speake, C; Skinner, SO; Berel, D; Whalen, E; Dufort, MJ; Young, WC; Odegard, JM; ... Long, SA; + view all (2019) A composite immune signature parallels disease progression across T1D subjects. JCI Insight 10.1172/jci.insight.126917. (In press). Green open access

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Abstract

At diagnosis, most people with type 1 diabetes (T1D) produce measurable levels of endogenous insulin, but the rate at which insulin secretion declines is heterogeneous. To explain this heterogeneity, we sought to identify a composite signature predictive of insulin secretion, using a collaborative assay evaluation and analysis pipeline that incorporated multiple cellular and serum measures reflecting beta cell health and immune system activity. The ability to predict decline in insulin secretion would be useful for patient stratification for clinical trial enrollment or therapeutic selection. Analytes from 12 qualified assays were measured in shared samples from subjects newly diagnosed with T1D. We developed a computational tool to identify a composite panel associated with decline in insulin secretion over 2 years after diagnosis. The tool employs multiple filtering steps to reduce data dimensionality, incorporates error-estimation techniques including cross-validation and sensitivity analysis, and is flexible to assay type, clinical outcome and disease setting. Using this novel analytical tool, we identified a panel of immune markers that, in combination, are highly associated with loss of insulin secretion. The methods used here represent a novel process for identifying combined immune signatures that predict outcomes relevant for complex and heterogeneous diseases like T1D.

Type: Article
Title: A composite immune signature parallels disease progression across T1D subjects
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1172/jci.insight.126917
Publisher version: https://doi.org/10.1172/jci.insight.126917
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Autoimmunity, Diabetes, Immunotherapy, Molecular pathology
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity
URI: https://discovery.ucl.ac.uk/id/eprint/10085671
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