A composite immune signature parallels disease progression across T1D subjects (Affymetrix Cohort 2)

We used an array-based bioassay whereby serum is used to induce transcription in healthy “reporter” leukocytes. Serum samples were obtained from control-arm subjects enrolled in 3 clinical trials evaluating immunotherapies in T1D that were conducted by the Immune Tolerance Network. The included trials evaluated immune-modifying therapy in new-onset T1D, with similar trial timecourses, primary outcomes, and data and sample collection. Total RNA was isolated from the reporter cell line for gene expression analysis. Subjects from the placebo arms of three 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. UPN727 cells were stimulated with serum collected at baseline visits (N= 40 subjects). Gene expression analysis was performed in order to evaluate the transcriptional signature associated with new onset T1D.