Expression profiling by high throughput sequencing
Summary
Biologic agents active in other autoimmune settings have had variable effectiveness in newly diagnosed type 1 diabetes (T1D) where treatment across therapeutic targets is accompanied by transient stabilization of C-peptide levels in some patients, followed by progression at the same rate as in control groups. Why disparate treatments lead to similar clinical courses is currently unknown. Here, we use integrated systems biology and flow cytometry approaches to elucidate immunologic mechanisms associated with C-peptide stabilization in T1D subjects treated with the anti-CD3 monoclonal antibody, teplizumab. This work is part of the Immune Tolerance Network AbATE study (Autoimmunity-Blocking Antibody for Tolerance in Recently Diagnosed Type 1 Diabetes); data are also available through the ITN TrialShare portal: https://www.itntrialshare.org/project/Studies/ITN027AIDB/Study%20Data/begin.view?.
Overall design
We performed bulk RNA-seq on 190 whole blood samples from visit months 0 (R: 14, NR: 16: C: 15, total: 45), 6 (R: 16, NR: 17, C: 15, total: 48), 12 (R: 13, NR: 14, C: 16, total: 43), and 24 (R: 17, NR: 20, C: 17, total: 54).
Long SA, Thorpe J, DeBerg HA, Gersuk V, Eddy J, Harris KM, Ehlers M, Herold K, Nepom GT, Linsley PS. Partially exhausted CD8 T cells are associated with clinical response to teplizumab in new-onset type 1 diabetes. Science Immunology 2016 Nov 18. Vol. 1, Issue 5. DOI:10.1126/sciimmunol.aai7793
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