B lymphocyte alterations accompany abatacept resistance in new-onset type 1 diabetes

Peripheral blood samples were collected from subjects enrolled in the TrialNet study TN-09. This was a phase II study of the effects of the T cell costimulation inhibitor CTLA4-Ig (abatacept) in new-onset T1D. Total RNA was isolated from whole blood samples and then globin-reduced. RNAseq libraries were prepared from the globin-reduced RNA. The abatacept trial was a randomized, double-blind study of patients (N = 112) with newly diagnosed T1D assigned to receive infusions of CTLA4-Ig (abatacept) or placebo on on days 1, 14, and 28, and then every 28 days with the last dose on day 700. The primary outcome was the baseline-adjusted geometric mean of the 2-h area-under-the-curve (AUC) serum C-peptide concentration after a mixed-meal tolerance test at 2 years’ follow-up. We obtained RNA-seq data from a subset of subjects in the original trial (N = 105 subjects originally), sampled at different visits (0, 84, and 728 days) for a total of 286 samples (mean 2.7 samples per patient). Of 286 initial samples, 272 yielded high-quality RNA-seq data consistent with subject annotation, and were used in downstream analyses.