A composite immune signature parallels disease progression across T1D subjects (RNA-Seq Cohort 2 Cell Sorted)

Peripheral blood mononuculear cells were thawed and sorted into B cell, CD4+ T cells, CD8+ T cells, and monocytes. Samples were obtained from control-arm subjects enrolled in 2 clinical trials evaluating immunotherapies in T1D that were conducted by the Immune Tolerance Network. The trials had similar study timepoints, clinical and metabolic measurements, and data and sample collection plans. Total RNA was isolated from the sorted cell populations and then RNAseq libraries were prepared. Overall design: Subjects from the placebo arms of 2 new onset T1D trials conducted by the Immune Tolerance Network were aggregated to evaluate the heterogeneity in the rates of insulin secretion decline. The outcome used for this analysis was the rate of decline in C-peptide as calculated by sequential 2 hour AUC of serum C-peptide after a mixed-meal tolerance test over the 2 years of each trial. We obtained RNA-seq data from the baseline visit (N=28 subjects) of participants in these trials. Of 112 libraries, 106 yielded high-quality RNA-seq data that were used in downstream analyses.